1. 中国幽门螺杆菌感染的流行病学现状
1.1 总体感染率与时间演变
幽门螺杆菌（Helicobacter pylori, H. pylori）感染在全球范围内普遍存在，但其流行率呈现下降趋势，尤其是在2011-2022年期间下降显著1。在中国，幽门螺杆菌的感染率也经历了显著的变化。根据1983-1994年间的数据，中国大陆地区的幽门螺杆菌总体感染率约为58.3%（95% CI: 50.7-65.5%）2。在更早期的研究中，1991年的一项荟萃分析显示，中国15-22岁健康志愿者的感染率为49.4%，而13-88岁有症状胃镜检查患者的感染率则高达64.5%3。这些早期数据表明，幽门螺杆菌感染在中国曾普遍存在。
进入21世纪后，中国的幽门螺杆菌感染率持续下降。一项涵盖1990年至2019年中国大陆地区数据的系统评价和荟萃分析显示，总感染率为44.2%（95% CI: 43.0-45.5%），估计有5.89亿人感染2。特别是近十年（2014-2023年）的数据，进一步证实了这一下降趋势。一项监测系统研究指出，成人幽门螺杆菌感染率从1983-1999年的63.3%显著下降至2015-2019年的38.7%4。儿童感染率也呈现类似趋势，从1983-1999年的23.1%下降到2015-2019年的15.7%4。
不同时间段的统计差异进一步突显了感染率的动态变化。具体而言：
- 1983-1994年：感染率处于较高水平，估计为58.3%2。
- 2000-2009年：成人感染率略有下降，为52.5%4。
- 2010-2014年：成人感染率进一步下降至43.4%4。
- 2015-2019年：感染率降至40.0%（95% CI: 38.2-41.8%）2，成人感染率为38.7%，儿童感染率为15.7%4。
总体来看，中国幽门螺杆菌感染率在过去几十年中呈现显著的下降趋势，尤其在最近十年内下降幅度更为明显。这与全球范围内幽门螺杆菌流行率的下降趋势相吻合，可能与卫生条件的改善、经济发展以及根除治疗的普及等因素有关15。然而，尽管感染率有所下降，但中国感染人群基数仍然庞大，提示仍需持续关注并采取有效防控措施2。
1.2 地域分布特征
中国幅员辽阔，不同地理区域的幽门螺杆菌感染率存在显著差异，这与当地的经济发展水平、卫生条件、饮食习惯以及地理环境等多种因素密切相关。
根据一项针对中国大陆地区1990年至2019年幽门螺杆菌感染率的系统评价和荟萃分析，西北地区的感染率相对较高，达到51.8%（95% CI: 47.5-56.1%），其次是华东地区（47.7%，95% CI: 45.4-50.0%）和西南地区（46.6%，95% CI: 42.1-51.1%）2。另一项覆盖2014-2023年的系统评价和荟萃分析也得出了相似的结论，指出西北地区的感染率最高，为51.3%（95% CI: 45.6-56.9%）6。2017年至2018年对中国18-64岁成年人进行的一项社区横断面研究显示，西北地区同样表现出最高的感染率，达到63.6%7。
具体到省份层面，青海省的幽门螺杆菌感染率尤其突出。一项2021年至2022年对青海省家庭的横断面研究显示，该省的感染率高达52.8%，家庭感染率更是达到80.6%8。在2014-2023年的全国数据中，青海省的感染率更是高达60.2%（95% CI: 46.5-73.9%）6。这可能与青藏高原地区的特殊环境和生活条件有关。高海拔缺氧环境可能加剧幽门螺杆菌感染引起的胃炎病理表现和炎症反应9。此外，青海等欠发达地区仍然保持较高的感染率10，这可能与较低的经济发展水平、不完善的卫生基础设施以及可能存在的家庭内聚集性感染有关811。例如，青海家庭中，共同生活人数越多，幽门螺杆菌感染率越高，且不使用公筷公勺的家庭感染率也更高8。
除了高海拔地区，中国北方的某些高风险区域，如太行山地区，也观察到幽门螺杆菌感染率较高，尤其是在山区，这可能与欠发达的生活条件和饮水卫生有关12。一项关于幽门螺杆菌在北中国分布的研究也指出，高胃癌风险地区（如庄河）的幽门螺杆菌毒力基因型（如vacA s1或s1m1b）频率高于低胃癌风险地区（如沈阳）13，暗示了环境因素对感染特征和疾病风险的影响。
民族差异也可能是地域分布特征的一个重要方面。例如，一项针对中国藏族和汉族人群幽门螺杆菌感染率的荟萃分析显示，藏族人群的感染率高于汉族，特别是在西藏地区或西北地区14。这提示遗传背景、文化习俗和社会经济因素在不同民族间的感染率差异中可能发挥作用。
总的来说，中国幽门螺杆菌感染的地域分布呈现出明显的差异性，西北地区，特别是青海省，表现出较高的感染率。这些差异受多种因素交织影响，包括地理环境（如高海拔）、社会经济发展水平、卫生条件、生活习惯以及民族特征等267101215。对这些地域差异的深入理解对于制定有针对性的防控策略至关重要。
1.3 人群分布特征
幽门螺杆菌感染在不同人群中呈现出显著的分布特征，其感染率受年龄、性别、职业以及家庭聚集性等多种因素的影响。
年龄分层感染率
幽门螺杆菌感染率随年龄增长而增加是普遍规律216。一项涵盖中国大陆1990年至2019年数据的荟萃分析显示，儿童和青少年群体的感染率为28.0%（95%CI: 23.9-32.5%），而成人感染率则上升至46.1%（95%CI: 44.5-47.6%）2。另一项针对2014-2023年中国幽门螺杆菌感染情况的系统综述和荟萃分析也指出，老年人的感染率显著高于儿童，分别为44.5%（95%CI: 41.9-47.1%）和27.5%（95%CI: 19.58-34.7%）6。全球范围内的研究也证实了这一趋势，0-6岁儿童的感染率为26.0%，7-12岁儿童为33.9%，而13-18岁青少年则达到41.6%16。这种随年龄增长的感染率升高，可能与累积暴露机会的增加、口腔卫生状况以及免疫系统功能等因素有关。
性别差异
在中国人群中，幽门螺杆菌感染率的性别差异并不总是显著。一项针对81,754名中国成年人的横断面研究显示，总体感染率为49.59%，其中男性感染率为49.74%，女性为49.3%，男女之间无显著差异17。然而，在不同年龄段，性别差异可能显现。例如，年轻女性的感染风险低于男性（OR=0.908, 95%CI: 0.868-0.95），而老年女性的感染风险则高于男性（OR=1.137, 95%CI: 1.041-1.243）17。此外，女性感染率与年龄在18至60岁之间呈正相关（Spearman相关系数为0.825，P<0.01）17。而在某些区域性研究中，如中国南方一项对5035名健康体检者的分析发现，男性感染率为35.5%，女性为34.3%，同样没有显著差异18。这与部分国际研究结果有所不同，例如马来西亚的一项研究显示，男性感染率（18.9%）显著高于女性（9.0%），尤其是在马来人群中19。这表明性别在幽门螺杆菌感染中的作用可能存在地域和民族特异性，并受年龄等因素的调节。
特殊职业群体
军人是幽门螺杆菌感染研究中一个值得关注的特殊群体。在全球范围内，军人幽门螺杆菌的总体感染率为32%（95%CI = 31-33）20。在亚洲地区，军人的感染率则更高，达到50.2%（95%CI = 49-51.4）20。中国军人幽门螺杆菌感染率也较高，部分地区甚至超过40%21。一项针对2013年中国17-24岁新兵的调查显示，总体感染率为46.5%22。值得注意的是，军龄与感染率呈正相关：服役不足一个月的感染率为46.6%，服役不足两年的为59.2%，而服役两年以上的则升至63.2%，差异具有统计学意义（P < 0.05）22。这可能与军营生活的集体住宿环境、共用餐具、水源等密切相关，增加了交叉感染的机会。此外，家庭聚集性是军人感染幽门螺杆菌的重要风险因素，以及生活环境和年龄也是相关因素2022。
传播模式
幽门螺杆菌的主要传播途径包括人-人传播，尤其是家庭内部传播11。最新的大规模、全国性、以家庭为基础的流行病学研究揭示，在中国家庭中，幽门螺杆菌的家庭感染率高达71.21%11。在已感染的家庭中，有19.70%的家庭所有成员均被感染11。儿童感染与父母感染之间存在显著关联，且家庭成员数量、居住在高感染率地区以及大家庭（如三口之家）是家庭感染的独立风险因素11。此外，未采用分餐制（如使用公勺公筷）以及较差的卫生习惯（如不洗碗使用洗涤剂、不削水果直接食用）也与感染风险增加有关1122。虽然水作为幽门螺杆菌潜在的传播媒介一直备受关注23，但在中国家庭中，经水传播的证据仍需进一步研究。
2. 幽门螺杆菌感染与相关疾病的关联及负担
2.1 胃癌的归因风险与疾病负担
幽门螺杆菌（H. pylori）感染被国际癌症研究机构（International Agency for Research on Cancer）列为I类致癌物，是胃癌发生发展的主要病因 24。全球约一半人口感染幽门螺杆菌，其中20%的感染者会发展为癌前病变，约2%的感染者最终会罹患胃癌 25。胃癌仍然是一个严重的全球健康挑战 26。
幽门螺杆菌感染与胃癌之间的关联具有显著的地域差异和肿瘤部位特异性。根据一项系统综述和荟萃分析，在亚洲人群中，幽门螺杆菌感染与非贲门胃癌（non-cardia gastric cancer, NCGC）存在强烈的正相关，其优势比（OR）为2.50（95%CI: 1.89-3.32），而在欧洲/北美地区，NCGC的优势比更高，达到5.37（95%CI: 4.39-6.57）。对于贲门胃癌（cardia gastric cancer, CGC），亚洲人群中也观察到正相关（OR=1.74, 95%CI: 1.38-2.19），但在欧洲/北美人群中则呈现负相关（OR=0.64, 95%CI: 0.51-0.79）27。另一项针对东亚和西方人群的研究也支持了这些发现，幽门螺杆菌感染与东亚NCGC（OR, 4.36; 95% CI: 3.54-5.37）和CGC（OR, 2.86; 95% CI: 2.26-3.63）显著相关 28。
幽门螺杆菌感染对胃癌的归因风险（Population Attributable Fraction, PAF）揭示了其在胃癌负担中的重要性。在亚洲，约79%的NCGC病例和62%的CGC病例可归因于幽门螺杆菌感染 27。东亚地区的数据进一步细化，幽门螺杆菌感染导致了71.2%的NCGC和60.7%的CGC 28。这些高归因比例表明，在中国等亚洲国家，幽门螺杆菌感染是胃癌发病的最主要驱动因素。
根据中国最新的胃癌发病数据，估算全国范围内幽门螺杆菌感染相关的胃癌病例数具有重要的公共卫生意义。假设2021-2035年期间，中国将有1000万例新发胃癌病例和560万例胃癌死亡病例 29。若沿用亚洲地区NCGC 79%和CGC 62%的归因比例，以及考虑到中国胃癌构成中NCGC和CGC的比例，可以大致推算出由幽门螺杆菌感染引起的胃癌病例数。虽然精确的全国感染相关胃癌病例数需要更详细的地区发病率和胃癌亚型分布数据，但可以肯定的是，这一数字将非常庞大，构成巨大的疾病负担。例如，一项研究预测，通过根除幽门螺杆菌可以避免7.6%-35.5%的新发胃癌病例 29。这凸显了幽门螺杆菌筛查和根除在胃癌一级预防中的关键作用 630。
此外，幽门螺杆菌感染通过诱导氧化应激、DNA损伤、慢性炎症和细胞凋亡等关键细胞事件，促进胃癌的发生发展 263132。慢性萎缩性胃炎（chronic atrophic gastritis, CAG）是胃癌的癌前病变之一，幽门螺杆菌阳性患者罹患CAG的风险比阴性患者高出约2.4倍 33。即使在幽门螺杆菌根除后，胃癌的风险依然存在，并且日本的研究表明，根除后发生的胃癌（GCAE）具有独特的内镜特征，通常是分化型癌症，且亚黏膜浸润的发生率较高 34。这表明，对高风险人群进行持续监测，即使在成功根除幽门螺杆菌后，也仍然是必要的。
总之，幽门螺杆菌感染是中国胃癌发病和死亡的主要可预防因素。其对NCGC和CGC的高归因风险，以及每年由此导致的大量胃癌新发病例，强调了将幽门螺杆菌筛查和根除纳入国家公共卫生策略的重要性，以有效降低胃癌的疾病负担 293536。
2.2 消化性溃疡与其他胃肠疾病
幽门螺杆菌（H. pylori）感染是多种胃肠道疾病，特别是消化性溃疡（Peptic Ulcer Disease, PUD）的主要病因 3738。在全球范围内，幽门螺杆菌感染影响了约一半的人口，若不进行治疗，感染通常会持续终生 3739。
消化性溃疡
幽门螺杆菌感染与消化性溃疡（包括胃溃疡和十二指肠溃疡）之间存在明确的因果关系 3740。消化性溃疡的发生通常源于胃粘膜慢性炎症和胃酸分泌紊乱 40。幽门螺杆菌通过多种机制导致溃疡形成：
- 破坏粘膜防御屏障：幽门螺杆菌分泌的尿素酶能产生氨，中和胃酸，使其能在酸性环境中存活，但同时氨对胃粘膜有直接毒性 37。此外，细菌产生的细胞毒素相关基因A（CagA）和空泡细胞毒素A（VacA）等毒力因子会直接损伤胃粘膜上皮细胞，并诱导炎症反应 3741。
- 改变胃酸分泌：幽门螺杆菌感染常导致慢性胃炎，进而影响胃泌素和生长抑素的分泌平衡，导致胃酸分泌异常 40。在十二指肠溃疡患者中，通常表现为胃酸分泌增加，而胃溃疡患者中则可能出现胃酸分泌正常或减少 3840。
- 诱发炎症反应：幽门螺杆菌感染引发的持续性炎症反应，导致大量炎症细胞浸润和细胞因子释放，进一步加剧粘膜损伤，最终形成溃疡 24。
多项研究证实了幽门螺杆菌感染在消化性溃疡中的重要作用。在中国18-64岁成年人中，幽门螺杆菌感染在胃溃疡患者中占58.6%，在十二指肠溃疡患者中占61.1% 7。一旦成功根除幽门螺杆菌，非NSAIDs（非甾体抗炎药）相关的胃和十二指肠溃疡即使不长期抑制胃酸也能愈合，更重要的是，消化性溃疡及其并发症很少复发 40。幽门螺杆菌根除仍然是减轻消化性溃疡疾病负担的首要任务 7。
慢性胃炎
幽门螺杆菌感染是导致慢性胃炎的最常见原因。几乎所有感染幽门螺杆菌的个体都会发展为慢性活动性胃炎，其临床表现可从无症状到严重的胃肠道疾病 3739。长期慢性炎症可导致胃粘膜萎缩性变化，进而发展为慢性萎缩性胃炎（Chronic Atrophic Gastritis, CAG）4243。CAG是胃癌的癌前病变，且幽门螺杆菌阳性患者患CAG的风险约为阴性患者的2.4倍 43。尽管幽门螺杆菌根除后萎缩性胃炎通常会有所改善，但对于已形成的肠上皮化生，其可逆性仍存在争议 44。
功能性消化不良
功能性消化不良（Functional Dyspepsia, FD）是指持续存在上腹部症状，但内镜检查未发现器质性病变的临床综合征 45。幽门螺杆菌感染与功能性消化不良之间的关系较为复杂和有争议 4046。虽然部分研究认为幽门螺杆菌感染与功能性消化不良没有直接的因果关系，但治疗感染可能会适度改善症状 40。然而，最新的指南建议，对于存在消化不良症状且年龄小于60岁的患者，应进行幽门螺杆菌检测，若阳性则进行根除治疗 45。一项随机安慰剂对照临床试验表明，某些益生菌菌株（如LG21）可以显著改善功能性消化不良的主要症状，其机制可能包括保护十二指肠粘膜免受有害肠道细菌侵害，从而解决小肠细菌过度生长问题 47。这提示幽门螺杆菌可能通过影响胃肠道微生态平衡，间接影响功能性消化不良的发生发展。
2.3 胃肠外疾病的潜在关联
除了胃肠道疾病，幽门螺杆菌（H. pylori）感染还与多种胃肠外疾病存在潜在关联，这些关联的机制通常涉及免疫调节、分子模拟以及系统性炎症反应 484950。虽然某些关联的因果关系仍有争议，但越来越多的流行病学和实验证据支持了幽门螺杆菌在某些胃肠外疾病发生发展中的作用 5152。
慢性荨麻疹
慢性荨麻疹（Chronic Spontaneous Urticaria, CSU）是一种常见的皮肤病，其病因复杂且常不明。越来越多的研究表明，幽门螺杆菌感染可能与CSU的发生有关 5253。在部分CSU患者中，成功根除幽门螺杆菌后，症状得到了显著缓解甚至消失 5253。这种关联的机制可能包括：
- 免疫调节和炎症反应：幽门螺杆菌感染引起的慢性炎症反应可导致全身性免疫失衡，诱导肥大细胞活化并释放组胺等炎症介质，从而引发或加重荨麻疹症状 5054。
- 分子模拟：幽门螺杆菌的一些蛋白可能与人体自身抗原结构相似，诱导交叉反应性抗体或T细胞反应，攻击自身组织，导致自身免疫性荨麻疹 54。例如，有研究通过生物信息学方法预测，幽门螺杆菌的某些蛋白（如伴侣蛋白GroEL）可能与人类HSP60等抗原存在交叉反应性表位，从而诱导自身免疫反应 54。
尽管幽门螺杆菌在CSU中的确切作用机制尚不完全清楚，但对于H1抗组胺药治疗无效的CSU患者，筛查并根除幽门螺杆菌已成为一种考虑的治疗策略 53。
自身免疫性疾病
幽门螺杆菌感染与多种自身免疫性疾病的关联已得到广泛研究，其中甲状腺炎和类风湿关节炎是较为突出的例子。
- 自身免疫性甲状腺疾病（如桥本甲状腺炎、格雷夫斯病）：幽门螺杆菌感染被认为是甲状腺自身免疫疾病的潜在诱发因素之一 55。研究表明，幽门螺杆菌感染，特别是CagA阳性菌株的感染，与成人隐匿性自身免疫性糖尿病（LADA）患者甲状腺过氧化物酶抗体（TPO Ab）和促甲状腺激素（TSH）水平升高呈正相关，提示其可能参与甲状腺自身免疫和腺体功能障碍的机制 56。分子模拟是解释这种关联最广泛接受的机制 55。然而，也有研究指出，幽门螺杆菌感染与桥本甲状腺炎患者血清中模仿人类ZnT8的幽门螺杆菌肽的抗体水平之间缺乏相关性，提示并非所有通过分子模拟机制介导的自身免疫反应都直接靶向ZnT8 57。
- 类风湿关节炎（Rheumatoid Arthritis, RA）：类风湿关节炎是一种慢性自身免疫性疾病，幽门螺杆菌感染与其发病风险之间的关系备受关注。一项基于台湾人群的全国性回顾性队列研究发现，幽门螺杆菌感染患者患RA的风险高于对照组，特别是在30岁以下人群中风险最高，尤其在年轻女性中更为显著 58。即使在随访1-5年和5年以上的患者中，幽门螺杆菌感染者患RA的风险仍分别高出1.43倍和1.44倍 58。这一关联的机制可能涉及：
其他胃肠外疾病
幽门螺杆菌感染还与其他一些胃肠外疾病存在流行病学关联，包括：
- 结直肠癌（Colorectal Cancer, CRC）：流行病学研究报告，幽门螺杆菌感染者患CRC的风险几乎增加一倍 4861。虽然幽门螺杆菌主要定植于胃部，但其可能通过调节宿主肠道免疫反应和诱导肠道菌群改变来增加CRC风险 48。肠道微生物组在CRC中起着关键作用，幽门螺杆菌感染不仅影响胃部菌群，还会导致远端大肠菌群组成的变化，从而促进肿瘤发展 48。
- 缺铁性贫血：幽门螺杆菌感染可导致铁吸收障碍和慢性失血，从而引起缺铁性贫血，尤其是在儿童和青少年中 4960。
- 特发性血小板减少性紫癜（Idiopathic Thrombocytopenic Purpura, ITP）：幽门螺杆菌感染与ITP之间存在较强的关联，成功根除幽门螺杆菌可使部分ITP患者的血小板计数恢复正常 6062。
- 神经系统疾病：越来越多的研究发现幽门螺杆菌与帕金森病、阿尔茨海默病、多发性硬化症和吉兰-巴雷综合征等神经系统疾病之间存在关联 495063。这些关联的机制可能涉及幽门螺杆菌通过释放毒素、诱导炎症或影响营养吸收（如维生素B12）来影响神经功能 4960。
- 代谢综合征和心血管疾病：幽门螺杆菌感染与代谢综合征、缺血性心血管疾病之间也存在潜在关联 606263。感染可能通过增加胰岛素抵抗和全身炎症反应来影响心血管健康 4963。
尽管幽门螺杆菌与多种胃肠外疾病存在关联，但许多关联的病理机制仍需深入研究，且需要更多高质量的随机对照试验来明确其因果关系和临床意义 515263。
3. 感染与致病的关键影响因素
3.1 细菌自身特性
幽门螺杆菌（H. pylori）感染的临床结局差异巨大，从无症状的慢性胃炎到消化性溃疡，再到胃癌，其致病性受到细菌自身多种毒力因子及其基因型差异的显著影响 246465。这些毒力因子通过与宿主细胞相互作用，调控炎症反应、细胞增殖、凋亡以及免疫逃逸等过程，进而决定疾病的严重程度和进展 6667。
主要毒力因子及其致病性
CagA（细胞毒素相关基因A）：CagA是幽门螺杆菌最重要的毒力因子之一，由位于致病性岛（cag PAI）上的_cagA_基因编码 246466。CagA蛋白通过细菌的IV型分泌系统（T4SS）注入宿主胃上皮细胞内 666768。进入细胞后，CagA会磷酸化并与多种宿主蛋白相互作用，干扰细胞信号通路，导致细胞形态学改变（如“蜂巢样”表型）、细胞增殖异常、细胞极性丧失、DNA损伤以及炎症反应加剧（如激活NF-κB信号通路，促进IL-8等促炎细胞因子分泌） 246970。CagA阳性菌株与胃癌、消化性溃疡等严重胃部疾病的风险增加密切相关 246471。值得注意的是，CagA的EPIYA基序（尤其是在东亚株中常见的ABD类型）和CM（CagA多态性）基序的基因型差异，如CM motif pattern D，被认为与胃癌风险显著相关 6972。还有研究发现，CagA蛋白稳定性受宿主因子AUF1调控，AUF1表达上调可抑制自噬溶酶体降解，稳定CagA，进而促进幽门螺杆菌诱导的炎症 73。
VacA（空泡细胞毒素A）：VacA是另一种重要的幽门螺杆菌毒力因子，可诱导宿主细胞形成空泡，并影响细胞膜通透性、线粒体功能和T细胞活化 246466。VacA基因存在多种多态性，主要表现为信号肽区（s1或s2）和中间区（m1或m2）的差异。s1m1基因型通常被认为毒性最强，与胃癌和消化性溃疡的风险增加相关 6471。一项针对山东地区幽门螺杆菌株的研究发现，vacA m1和c1基因型在胃癌患者中显著更为常见，其中_vacA_ c1基因型被认为是山东男性55岁以上胃癌的独立风险指标 72。VacA还能抑制T细胞增殖，促进免疫逃逸 67。
HtrA（高温要求蛋白A）：HtrA是一种分泌型丝氨酸蛋白酶，在幽门螺杆菌感染的早期阶段发挥关键作用 6774。它不仅参与细菌的定植，还能降解宿主细胞间的紧密连接蛋白（如Occludin和E-cadherin），破坏胃上皮屏障功能，促进细菌穿透上皮层，并协助CagA蛋白的注入 676974。HtrA蛋白的活性增强与更强的致病性相关。
HtrA蛋白S171L单核苷酸多态性与胃癌风险
近期研究发现，幽门螺杆菌HtrA蛋白上的一个单核苷酸多态性（Single-Nucleotide Polymorphism, SNP）——丝氨酸到亮氨酸的改变（S171L）与胃癌的发生发展显著相关 6974。具体而言：
- 功能增强：171L型HtrA突变体能够促进HtrA三聚体的形成，并显著增强其蛋白水解活性 74。这意味着171L型HtrA能更有效地裂解上皮细胞连接蛋白，如Occludin和肿瘤抑制基因E-cadherin，从而严重损害上皮屏障 74。
- 促进CagA注射和炎症：与171S型HtrA相比，含有171L型HtrA的幽门螺杆菌会引起更严重的上皮损伤，增强致癌蛋白CagA向宿主细胞的注射 74。这进一步加剧了NF-κB介导的炎症反应和细胞增殖（通过β-catenin的核积累），并促进宿主DNA双链断裂，最终诱发恶性转化 6974。
- 潜在生物标志物：这些发现表明，171S/L HtrA突变是幽门螺杆菌中一个独特的癌症相关SNP，有望作为幽门螺杆菌感染胃癌风险预测的潜在生物标志物 6974。
除了上述毒力因子，幽门螺杆菌还具有其他重要的致病特性，如鞭毛（辅助细菌在粘液层中运动和定植）75、尿素酶（中和胃酸，帮助细菌在胃部存活）76、外膜蛋白（OMPs，介导细菌与宿主细胞的粘附）68以及生物膜形成能力（可能增加对抗生素的耐药性）76等。这些细菌自身特性，特别是毒力因子基因型的多样性，共同决定了幽门螺杆菌感染的复杂临床表现和疾病进展风险。
3.2 抗生素耐药性现状
幽门螺杆菌（H. pylori）对常用抗生素的耐药性是导致其根除治疗失败的主要原因，也是当前中国乃至全球面临的严峻挑战 77。了解不同地区、不同时间段的抗生素耐药谱对于制定有效的根除治疗方案至关重要 78。
中国总体抗生素耐药率
多项系统评价和荟萃分析显示，中国幽门螺杆菌对多种常用抗生素的耐药率较高且呈现动态变化。
- 克拉霉素（Clarithromycin）：克拉霉素是中国幽门螺杆菌根除治疗方案中的关键药物。然而，其耐药率持续走高。2016-2020年的数据显示，中国幽门螺杆菌对克拉霉素的耐药率达到34%（95% CI: 30-39%）78。更晚近的分析（1990-2022年亚太地区数据）显示，最新克拉霉素耐药率已升至30%（95% CI: 28-33%）79。2023年的一项研究指出，中国成人对克拉霉素的耐药率为23.76%（95% CI: 20.23%, 27.3%）80。另一项针对2000-2023年中国大陆地区的研究显示，克拉霉素的总体耐药率为30.72%（95% CI: 27.53%-33.99%）81。
- 甲硝唑（Metronidazole）：甲硝唑是临床常用的一线药物。然而，其耐药率在中国一直处于高位。2016-2020年，甲硝唑的耐药率为78%（95% CI: 73-84%）78。1990-2022年亚太地区最新数据显示，甲硝唑耐药率达到61%（95% CI: 55-66%）79。2023年研究显示中国成人对甲硝唑的耐药率高达69.32%（95% CI: 64.85%, 73.8%）80。2000-2023年中国大陆地区研究则报告其耐药率为70.14%（95% CI: 29.53%-37.46%）81。甲硝唑的高耐药率显著影响了包含该药物的治疗方案的疗效 82。
- 左氧氟沙星（Levofloxacin）：左氧氟沙星是挽救性治疗方案中的重要组成部分。2016-2020年，中国幽门螺杆菌对左氧氟沙星的耐药率为35%（95% CI: 30-40%）78。1990-2022年亚太地区最新数据显示，左氧氟沙星耐药率升至35%（95% CI: 31-39%）79。2023年研究报告中国成人对左氧氟沙星的耐药率为29.45%（95% CI: 4.90, 176.96）80。2000-2023年中国大陆地区研究显示其耐药率为32.98%（95% CI: 28.73%-37.37%）81。
- 阿莫西林（Amoxicillin）：阿莫西林的耐药率相对较低且保持稳定。2016-2020年为3%（95% CI: 1-5%）78。亚太地区最新数据为6%（95% CI: 4-8%）79。2023年中国成人耐药率为1.35%（95% CI: 1.03%, 1.68%）80。2000-2023年中国大陆地区研究显示为2.41%（95% CI: 1.43%-3.60%）81。
- 四环素（Tetracycline）：四环素的耐药率也较低且稳定。2016-2020年为2%（95% CI: 1-4%）78。亚太地区最新数据为4%（95% CI: 2-6%）79。2000-2023年中国大陆地区研究显示为2.53%（95% CI: 1.19%-4.28%）81。
- 呋喃唑酮（Furazolidone）：呋喃唑酮的耐药率一直处于非常低的水平。2016-2020年为1%（95% CI: 0-4%）78。2000-2023年中国大陆地区研究显示为1.54%（95% CI: 0.28-3.62%）81。
总体而言，中国幽门螺杆菌对克拉霉素、甲硝唑和左氧氟沙星的耐药率较高并呈上升趋势，而对阿莫西林、四环素和呋喃唑酮的耐药率则较低且相对稳定 7778。
区域差异
幽门螺杆菌抗生素耐药性在中国不同地区存在显著差异 7881。
- 克拉霉素耐药性：北方（37%，95% CI: 32-41%）和西部（35%，95% CI: 17-54%）地区的克拉霉素耐药率高于南方（24%，95% CI: 17-32%）和东部（24%，95% CI: 20-28%）地区 78。
- 甲硝唑耐药性：不同区域的甲硝唑耐药率普遍较高，且存在一定差异。
- 左氧氟沙星耐药性：与克拉霉素类似，左氧氟沙星耐药率也表现出区域差异。
例如，一项对湖南省幽门螺杆菌抗生素耐药性的多中心研究（2022年4月至2023年4月）显示：
- 克拉霉素耐药率为49.2%，远高于全国平均水平 83。
- 左氧氟沙星耐药率为37.8%，也高于全国平均水平 83。
- 甲硝唑耐药率为76.1%，与全国高耐药率趋势一致 83。
- 阿莫西林、呋喃唑酮和四环素的耐药率分别为2.3%、1.4%和0.7%，保持在较低水平 83。
湖南省中部地区的整体耐药率高于其他地区 83。这些区域差异可能与当地抗生素使用习惯、经济发展水平以及人群流动性等因素有关。
年龄、胃疾病类型与耐药性
耐药率还受到患者年龄和胃疾病类型的影响：
- 年龄：湖南省的研究发现，幽门螺杆菌对克拉霉素和左氧氟沙星的耐药率在不同年龄组间存在显著差异（p < 0.05），老年组的耐药率高于年轻组 83。
- 胃疾病类型：在湖南省的研究中，萎缩性胃炎患者对克拉霉素的耐药率更高，而消化性溃疡患者对左氧氟沙星的耐药率最低 83。这提示不同的病理生理状态可能影响细菌的耐药基因表达或菌株选择压力。然而，也有研究表明，消化性溃疡患者对克拉霉素的耐药率可高达50%，对甲硝唑的耐药率可达67.5% 84。此外，幽门螺杆菌再感染也可能影响抗生素耐药性。
下表总结了中国幽门螺杆菌对主要抗生素的耐药率：
| 抗生素 | 2016-2020年耐药率 78 | 1990-2022年最新亚太地区耐药率 79 | 2023年中国成人耐药率 80 | 2000-2023年中国大陆耐药率 81 | 湖南省 (2022-2023) 耐药率 83 |
|---|---|---|---|---|---|
| 克拉霉素 | 34% (30-39%) | 30% (28-33%) | 23.76% (20.23-27.3%) | 30.72% (27.53-33.99%) | 49.2% |
| 甲硝唑 | 78% (73-84%) | 61% (55-66%) | 69.32% (64.85-73.8%) | 70.14% (29.53-37.46%) | 76.1% |
| 左氧氟沙星 | 35% (30-40%) | 35% (31-39%) | 29.45% (4.90-176.96) | 32.98% (28.73-37.37%) | 37.8% |
| 阿莫西林 | 3% (1-5%) | 6% (4-8%) | 1.35% (1.03-1.68%) | 2.41% (1.43-3.60%) | 2.3% |
| 四环素 | 2% (1-4%) | 4% (2-6%) | - | 2.53% (1.19-4.28%) | 0.7% |
| 呋喃唑酮 | 1% (0-4%) | - | - | 1.54% (0.28-3.62%) | 1.4% |
值得注意的是，耐药性可能会在治疗失败后升高 81。例如，多次根除治疗失败的患者可能会出现多重耐药性，如对克拉霉素和甲硝唑同时耐药的情况并不少见 8586。因此，持续监测幽门螺杆菌的抗生素耐药谱对于优化临床决策和指南推荐至关重要 81。
3.3 宿主与环境因素
幽门螺杆菌（H. pylori）感染的发生、发展及其导致的疾病结局，不仅取决于细菌自身的毒力因子，更受到宿主遗传背景、免疫状态以及复杂环境因素的综合影响 8788。
宿主遗传易感性
宿主基因多态性在决定个体对幽门螺杆菌感染的易感性及其相关疾病的进展中发挥着关键作用。其中，p27Kip1（通常简称p27）是一种细胞周期依赖性激酶抑制剂，其表达水平与幽门螺杆菌感染引起的胃癌风险密切相关。
- p27表达水平与胃癌风险：p27能够刺激胃上皮细胞凋亡并抑制细胞增殖。研究发现，幽门螺杆菌感染会降低p27的表达水平，而低水平的p27与胃癌的不良预后相关 89。对缺乏p27Kip1基因的小鼠进行研究发现，p27缺陷小鼠即使未感染幽门螺杆菌也会出现胃增生，而在感染幽门螺杆菌后，p27缺陷小鼠更容易发展为肠化生，并在60周后有7/12的小鼠（58.3%）出现显著的异型增生和胃癌，这与人类肠型胃癌的发生过程高度吻合 89。相比之下，野生型小鼠在75周感染后才出现肠化生，且仅1只动物出现显著胃异型增生，这表明p27缺失与幽门螺杆菌感染协同作用，显著增加了胃癌的发生风险 89。另一项针对胃癌患者的研究也发现，p27表达与幽门螺杆菌感染呈负相关（p < 0.01），即幽门螺杆菌感染的患者p27表达水平更低。在高度或中度分化的胃癌患者中，p27的表达显著高于低分化胃癌患者（p < 0.01） 90。这提示p27可能是幽门螺杆菌感染导致胃黏膜癌变过程中的一个关键指标，其在胃癌发展和进展中的作用使其成为临床诊断幽门螺杆菌感染胃癌的潜在辅助指标 90。
宿主免疫状态
宿主的免疫反应是幽门螺杆菌感染结局的另一个重要决定因素。幽门螺杆菌能够通过多种机制逃逸宿主免疫清除，并诱导慢性炎症，最终导致组织损伤和疾病进展 8891。
- 先天免疫：胃部的先天免疫系统（包括胃上皮细胞和髓系细胞）需要精确地与共生菌群、外源病原体、摄入物质和内源性脱落细胞相互作用，以维持内环境稳态。幽门螺杆菌感染能够极大地改变胃肠道微生物组和免疫细胞的组成 92。在无症状感染者中，NKp44+ ILC3s（自然杀伤细胞受体p44阳性的第三组固有淋巴细胞）在胃黏膜中的比例显著增加，并且与某些微生物类群的丰度相关。此外，CD11c+髓系细胞和活化的CD4+ T细胞及B细胞在幽门螺杆菌感染者中也显著扩增，B细胞表现出激活表型并进展到高度增殖的生发中心阶段和浆细胞成熟，这与胃固有层内三级淋巴结构的形成有关 92。然而，先天免疫的持续激活也可能通过促进慢性感染和纤维化，为肿瘤发展创造有利环境 88。
- 适应性免疫：幽门螺杆菌诱导的慢性炎症是胃癌发生的重要驱动因素。细菌的毒力因子，如CagA和VacA，能够调节宿主免疫反应，诱导Th1/Th17型免疫应答，导致大量炎症介质的释放，从而促进胃黏膜损伤和癌变 91。
环境因素
卫生条件、饮食结构和家庭聚集性是影响幽门螺杆菌感染率和疾病进展的关键环境因素 879394。
- 卫生条件：不卫生的生活条件、低社会经济地位和拥挤的居住环境与幽门螺杆菌感染的高流行率密切相关 94。改善饮水和食物卫生是降低感染风险的重要措施 93。例如，在发展中国家和新兴工业化国家，幽门螺杆菌感染率仍然保持在高水平，这与当地较差的卫生条件紧密相关 93。
- 饮食结构：饮食习惯对幽门螺杆菌感染的易感性及其引起的疾病进展具有重要影响。
- 家庭聚集性：家庭是幽门螺杆菌传播的主要场所 94。一项在中国进行的大规模家庭流行病学研究显示，幽门螺杆菌的家庭感染率高达71.21% 11。在已感染的家庭中，有19.70%的家庭所有成员均被感染 11。儿童感染与父母感染之间存在显著关联，提示了亲代传播的重要性 11。家庭成员数量多、居住在高感染率地区以及大家庭（如三口之家）是家庭感染的独立风险因素 11。此外，不使用公勺公筷等不当的饮食习惯也会增加家庭内传播的风险 11。这些发现强调了从个体治疗向家庭管理转变的必要性，这对于感染控制和相关疾病预防具有重要的临床和公共卫生意义 11。
综上所述，幽门螺杆菌感染的结局是细菌、宿主和环境因素复杂相互作用的结果。深入理解这些影响因素，有助于制定更精准的预防和治疗策略。
4. 幽门螺杆菌防控策略与实践效果
4.1 筛查与诊断技术
幽门螺杆菌（H. pylori）感染的准确诊断是制定有效治疗策略和评估流行病学现状的基础 95。目前，临床上存在多种侵入性（需要胃镜检查）和非侵入性诊断方法，各有其适用场景、优缺点以及对感染率统计的影响 96。
非侵入性检测方法
非侵入性检测方法因其操作简便、对患者创伤小而广泛应用于初筛、流行病学调查和治疗后评估，尤其适用于儿童和大规模筛查 9596。
尿素呼气试验（Urea Breath Test, UBT）：
- 原理与优势：UBT是目前最常用的非侵入性诊断方法之一，尤其以碳13（$^{13}$C-UBT）和碳14（$^{14}$C-UBT）为标记物。其原理是幽门螺杆菌产生的尿素酶能将口服的标记尿素水解为氨和二氧化碳（CO$_2$），后者经血液循环排出体外，通过检测呼气中的标记CO$_2$浓度来判断感染 96。UBT具有高灵敏度（90-95%）和高特异性（95-100%），并且能够区分活动性感染和既往感染，因此被广泛认为是诊断活动性感染和评估根除效果的“金标准” 969798。
- 应用场景与适应性：UBT在中国乃至全球均被广泛应用于幽门螺杆菌的初筛和根除治疗后的复查。由于其非侵入性，特别适合儿童（尽管需要一定的配合度）和不适合胃镜检查的患者 95。然而，其准确性可能受到抗生素、质子泵抑制剂（PPIs）或铋剂等药物的影响，因此在检测前需停药一段时间 9698。
- 对感染率统计的影响：UBT检测的感染率通常反映的是活动性感染。在一些流行病学调查中，UBT记录的感染率往往较高，例如一项对2014-2023年中国幽门螺杆菌感染率的荟萃分析显示，UBT测得的感染率为43.7%（95%CI: 41.4-46.0%） 6。
粪便抗原检测（Stool Antigen Test, SAT）：
- 原理与优势：SAT通过检测粪便中的幽门螺杆菌抗原来诊断感染，通常采用酶联免疫吸附法（ELISA） 9596。SAT的优势在于非侵入性、操作简便、成本较低，并且也适用于儿童和大规模筛查 9599。
- 应用场景与适应性：SAT在儿童诊断中表现出良好的准确性，特别是使用单克隆抗体（monoclonal antibody, MAb）的ELISA试剂盒，其 pooled 灵敏度为92.1%，特异性为94.1% 99。在中国人群中，HpSA和Apollo两种粪便抗原检测方法均表现出可接受的灵敏度和优秀的特异性（HpSA: 灵敏度86.4%，特异性100%；Apollo: 灵敏度90.9%，特异性97.6%） 100。与UBT类似，SAT也应在停用抗生素和PPIs后进行 9698。
- 对感染率统计的影响：SAT检测的感染率也反映活动性感染，在流行病学研究中与UBT结果具有可比性。其便捷性使其成为大规模筛查的有力工具 95。
血清抗体检测（Serology）：
- 原理与优势：血清抗体检测通过检测血液中幽门螺杆菌特异性抗体（主要是IgG）来判断是否感染 96。其优势在于操作简便、成本低、不依赖于活动性感染（即无需停药），且适用于筛查和流行病学研究 96 101。
- 应用场景与适应性：血清抗体检测常用于大规模流行病学调查和初步筛查。然而，其主要局限性在于不能区分活动性感染和既往感染，因为抗体在成功根除后仍可能持续存在数月甚至数年 9698。
- 对感染率统计的影响：由于无法区分活动性感染和既往感染，血清抗体检测得到的感染率通常会高于其他检测方法，特别是在感染率下降的地区，可能会高估当前活动性感染的比例 101。例如，一项对中国7241名受试者的研究发现，Hp-ELISA方法的感染率为41.87%，而组织学方法（Hp-HE）则为70.14%，但两者间相关性并不强，且易受吸烟和胃病状态影响 101。因此，在解读基于血清学方法得到的感染率数据时，需要特别注意其临床意义。
实时定量聚合酶链反应（qPCR）：
侵入性检测方法
侵入性检测方法需要通过胃镜检查获取胃黏膜活检组织，通常用于有报警症状的患者、需要进行病理诊断或抗生素敏感性测试的情况 9698。
快速尿素酶试验（Rapid Urease Test, RUT）：
组织学检查（Histology）：
细菌培养（Culture）：
检测方法对感染率统计的影响
不同的检测方法对幽门螺杆菌感染率的统计结果存在显著影响 6。
- 灵敏度与特异性差异：检测方法的灵敏度和特异性直接决定了其发现真阳性和真阴性的能力。例如，血清学检测由于无法区分新旧感染，其报告的“感染率”可能包含已自愈或根除的患者，从而高估了活动性感染率。
- 适用人群差异：非侵入性方法适合大规模筛查，能更广泛地反映普通人群的感染状况。侵入性方法多用于有症状或需要内镜检查的患者，其结果可能偏向于有胃部疾病的人群，因此其感染率可能高于一般人群。
- 诊断标准差异：一些研究可能采用单一方法作为诊断标准，而另一些研究可能采用两种或两种以上方法的组合（“金标准”定义），这都会导致感染率的统计偏差。例如，一项比较血清学和组织学方法的中国研究发现，组织学方法（Hp-HE）测得的感染率为70.14%，而血清学方法（Hp-ELISA）测得的感染率为41.87%，两者差异显著 101。
因此，在解读和比较不同研究的幽门螺杆菌感染率时，必须充分考虑所采用的诊断方法及其固有的局限性。为了提高感染率统计的准确性，未来的流行病学调查应尽量采用多种方法组合诊断，并明确报告所用方法的详细信息。
4.2 根除治疗的临床实践
幽门螺杆菌（H. pylori）的根除治疗是预防和治疗多种胃肠道疾病，尤其是胃癌和消化性溃疡的关键。然而，不断上升的抗生素耐药性为根除治疗带来了巨大挑战 105。近年来，中国对幽门螺杆菌根除治疗方案进行了持续优化和更新。2022年中国幽门螺杆菌根除治疗指南（2022 Chinese national clinical practice guideline on Helicobacter pylori eradication treatment）为当前和未来的临床实践提供了重要指导 105。
主要根除方案及疗效
目前，基于抗生素耐药现状和临床疗效，铋剂四联疗法和高剂量双联疗法是中国指南推荐的主要方案 105106。
铋剂四联疗法（Bismuth-containing Quadruple Therapy, BQT）：
- 组成与推荐：BQT通常由一种质子泵抑制剂（PPI）或钾离子竞争性酸阻滞剂（P-CAB）、两种抗生素（如阿莫西林、克拉霉素、甲硝唑、左氧氟沙星、四环素、呋喃唑酮）和一种铋剂组成 105106。铋剂因其廉价、安全、有效而被推荐为初始和挽救治疗的首选 105。
- 疗效：BQT被广泛认为是治疗幽门螺杆菌感染的一线方案，其根除率可达89.4%（改良意向性治疗分析）至90.9%（符合方案分析） 107。一些研究表明，在初次治疗中，BQT的根除率甚至可以达到90%以上 107108。例如，一项对比研究显示，10天VHA-dual（伏诺拉生20mg bid + 阿莫西林750mg qid）与BQT（埃索美拉唑20mg + 铋剂200mg + 阿莫西林1000mg + 克拉霉素500mg bid）在符合方案分析下的根除率分别为93.4%和90.9% 107。
- 治疗时长：关于BQT的最佳疗程，研究表明10天疗程与14天疗程的疗效相当，但不良反应发生率更低 109110。一项涉及1300名患者的多中心随机对照研究显示，10天铋剂四联疗法（包含伏诺拉生）在非劣效性方面与14天疗法相似，且不良反应发生率较低（22.59% vs. 28.50%，p=0.016） 110。因此，10天BQT可能代表了最佳治疗持续时间 109。
- 局限性：尽管BQT疗效显著，但其药物组成复杂，可能导致患者依从性下降和不良反应增多，如恶心、呕吐、腹泻和味觉异常等 106107。
高剂量双联疗法（High-Dose Dual Therapy, HDDT）：
- 组成与推荐：HDDT通常包括一种高效酸抑制剂（如P-CAB，特别是伏诺拉生）和高剂量阿莫西林 105。P-CAB类药物，如伏诺拉生（vonoprazan），能够提供更强效、更持久的胃酸抑制，从而增强阿莫西林的抗菌活性，这对于提高双联疗法的根除率至关重要 111112。
- 疗效：HDDT在经验性治疗中与BQT疗效相当，且具有更好的耐受性和依从性 105106108。例如，伏诺拉生-阿莫西林双联疗法（VHA-dual）在初次治疗中的根除率可达90%以上，且不良反应发生率显著低于BQT 107112。一项荟萃分析显示，VHA双联疗法在总体根除率（意向性治疗分析：86.0% vs. 80.7%；符合方案分析：90.6% vs. 85.7%）和不良事件发生率（15.4% vs. 27.7%）方面均优于其他指南推荐疗法 112。
- 阿莫西林剂量：关于HDDT中阿莫西林的最佳剂量，研究表明高剂量（例如伏诺拉生+1000mg阿莫西林 tid）与低剂量（例如伏诺拉生+1000mg阿莫西林 bid）的疗效和安全性相似 113114。这提示在高剂量伏诺拉生背景下，过高剂量的阿莫西林可能并非必需，甚至低剂量阿莫西林双联疗法（LVA-dual）在根除率方面非劣于高剂量阿莫西林双联疗法（HVA-dual） 114。
- 治疗时长：10天或14天的VHA双联疗法显示出优越的疗效和安全性，应优先考虑 112。
- 新进展：除了伏诺拉生，伊拉哌唑（ilaprazole）等新型酸抑制剂也被探索用于HDDT。一项研究发现，14天伊拉哌唑-阿莫西林高剂量双联疗法在根除率（ITT和PP分析均为76.3% vs. 61.3%）和安全性方面均优于BQT 115。
耐药性背景下的个体化治疗策略
随着抗生素耐药性的不断加剧，经验性治疗的成功率受到威胁 116117。因此，个体化治疗策略变得越来越重要 106117。
药物敏感性检测指导治疗（Susceptibility-Guided Therapy, SGT）：
- 必要性：当标准经验性治疗方案失败，或当地耐药率较高时，进行药物敏感性检测（AST）对指导后续治疗至关重要 118。AST可以帮助医生选择对患者感染菌株敏感的抗生素，从而显著提高根除率 119。
- 优势：一项荟萃分析显示，SGT作为一线治疗，其根除率显著高于BQT（意向性治疗分析：86% vs. 78%） 119。SGT不仅能提高疗效，还能减少不必要的抗生素使用，从而延缓耐药性的发展 117。
- 方法：传统的AST需要进行胃镜活检并培养细菌，耗时且操作复杂。然而，近年来非侵入性的分子检测方法发展迅速，例如通过粪便样本进行PCR检测，可以快速、准确地检测幽门螺杆菌及其克拉霉素和左氧氟沙星耐药基因突变 117120121。一项真实世界研究显示，通过粪便PCR检测指导的个体化治疗，总体根除率高达91.0% 120。
挽救性治疗（Rescue Therapy）：
- 对于初次治疗失败的患者，应根据之前的治疗方案、不良反应和当地耐药情况，选择不同的挽救性治疗方案。通常会选择含有不同抗生素组合的BQT或HDDT，并且强烈推荐在挽救治疗前进行药敏试验指导用药 106。
患者依从性管理：
综上所述，当前幽门螺杆菌根除治疗的临床实践主要依赖于铋剂四联疗法和高剂量双联疗法，并强调个体化治疗策略的重要性。随着抗生素耐药性的不断演变，结合药物敏感性检测指导用药，特别是利用非侵入性分子诊断技术，将成为未来提高根除率的关键。
4.3 公共卫生干预效果
幽门螺杆菌（H. pylori）感染与胃癌之间明确的因果关系，使得大规模筛查和根除幽门螺杆菌成为预防胃癌的重要公共卫生策略。多项社区干预项目，尤其是在胃癌高发地区开展的项目，已证实了其在降低胃癌发病率方面的潜力，但也揭示了实施过程中的成本效益和挑战 293035123124125。
社区筛查-根除项目对胃癌发病率的影响
中国林县项目：中国林县（Linqu County）是胃癌高发区。一项在该地区进行的社区随机对照干预试验，对幽门螺杆菌阳性居民进行了根除治疗。在长达11.8年的随访中，接受抗幽门螺杆菌治疗的个体胃癌发病率适度降低（风险比 [HR] 0.86, 95% CI 0.74-0.99）35。对于成功根除幽门螺杆菌的个体，胃癌发病率降低效果更为显著（HR 0.81, 95% CI 0.69-0.96）35。另一项长达26.5年的随访研究也显示，幽门螺杆菌根除治疗组的胃癌发病率低于安慰剂组（HR 0.57, 95% CI 0.33-0.98），尤其是在基线无癌前病变或无消化不良症状的个体中效果更明显 126。这些结果强烈支持了幽门螺杆菌大规模筛查和根除作为胃癌预防公共卫生政策的潜力 35。
台湾地区项目：台湾地区也开展了类似的社区干预项目。一项在彰化县（Changhua County）进行的随机临床试验，邀请50-69岁居民进行幽门螺杆菌粪便抗原（HPSA）检测。虽然意向性分析未能显示HPSA+FIT（粪便免疫化学试验）组与单纯FIT组在胃癌发病率或死亡率上的显著差异，但在调整筛查参与率和随访时间等因素后，HPSA+FIT组的胃癌发病率较低（0.79 [95% CI, 0.63-0.98]）127。这些结果表明，在胃癌高风险地区进行幽门螺杆菌的群体筛查和根除是有效和可行的 123。
成本效益分析
幽门螺杆菌筛查和根除的成本效益是实施大规模公共卫生干预的关键考量因素。多项研究表明，在胃癌高发区，该策略是具有成本效益的，甚至可能具有成本节约效益 29128129130131。
- 总体成本效益：对于胃癌高风险人群，筛查和根除幽门螺杆菌被认为具有成本效益 125129。一项针对中国人群的决策分析模型预测，在2021-2035年期间，幽门螺杆菌根除是一种成本节约的策略，可以避免7.6%至35.5%的新发胃癌病例 29。另一项中国的成本效益分析显示，在无症状人群中进行幽门螺杆菌筛查和根除治疗是具有成本效益的，其中每三年或五年进行一次筛查相比每年筛查具有更低的增量成本效益比（ICER）130。
- 最佳筛查策略：研究发现，不同的筛查方式具有不同的成本效益。例如，血清学检测作为筛查手段被证明是成本效益高的，其最低ICER为每获得生命年（LYG）1230美元，每获得质量调整生命年（QALY）1500美元 128。尿素呼气试验（UBT）也被认为是伊朗等国最具成本效益的筛查策略 131。
- 整合现有医疗计划：为了优化资源利用，可以将幽门螺杆菌筛查整合到现有的医疗计划中，例如结直肠癌筛查项目，这样可以提高患者依从性并节省成本 123124127。
实施挑战
尽管幽门螺杆菌筛查和根除策略前景广阔，但在大规模实施过程中仍面临诸多挑战。
治疗依从性：幽门螺杆菌的根除治疗通常涉及多种药物的联合使用，并可能引起不良反应，导致患者依从性不佳 132133。低依从性是导致治疗失败的重要原因 132。一项研究显示，药剂师的咨询和随访显著提高了患者的用药依从性（45.0% vs. 27.5%）和幽门螺杆菌根除率（42.5% vs. 28.5%）132。此外，基于新媒体的教育干预（NME），如微信等，也显著提高了患者依从性（90.5% vs. 73%）和根除率（81.9% vs. 67%），尤其是在服用四联疗法、年轻患者和中低收入国家中效果更佳 134。这些表明通过加强患者教育和支持可以有效提高依从性。
抗生素耐药性：长期大规模使用抗生素可能导致幽门螺杆菌耐药性的增加，从而影响根除治疗的成功率 124125135。为了应对这一挑战，需要制定基于当地耐药谱的治疗方案，并强调抗生素管理和个体化治疗的重要性 123124。
区域资源差异：不同地区在医疗资源、经济发展水平和公众健康意识方面存在显著差异，这使得在全国范围内统一推行大规模筛查和根除项目面临挑战 29。高风险地区可能更迫切需要干预，但可能同时面临资源限制。
“点石成金”的临界点（Point of No Return）：有观点认为，一旦胃黏膜病变进展到一定程度（如高级别萎缩或肠上皮化生），即使根除幽门螺杆菌，胃癌的风险也可能无法完全逆转 123136。这提示干预的最佳时机是在癌前病变发生之前或早期，因此年轻人群的筛查可能更具效益 123124。
总之，中国的社区幽门螺杆菌筛查和根除项目在降低胃癌发病率方面展现了巨大的潜力，并被证明是成本效益高的公共卫生策略。然而，要实现其最大效益，必须克服治疗依从性、抗生素耐药性以及区域资源差异等挑战，并通过持续的患者教育和个体化治疗方案来优化干预效果。
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参考文献
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Yunhao Li, Horace Choi, Kathy Leung, et al.
Lancet Gastroenterol Hepatol. 2023 Jun;8(6):553-564. doi: 10.1016/S2468-1253(23)00070-5. Epub 2023 Apr 20.
BACKGROUND: Few studies have examined the temporal trends of Helicobacter pylori prevalence worldwide. We aimed to identify the changes in global prevalence of H pylori infection between 1980 and 2022. METHODS: In this systematic review and meta-analysis, we searched PubMed, Embase, MEDLINE, Scopus, and Web of Science, with no language restrictions, for observational studies on the prevalence of H pylori infection published between Jan 1, 1980, and Dec 31, 2022. Conference papers, meta-analyses, reviews, and case reports were excluded. We divided the study timeframe into four periods: 1980-90, 1991-2000, 2001-10, and 2011-22. Summary data were extracted from each selected publication. The prevalence of H pylori and its temporal trend were analysed according to WHO region, World Bank income level, WHO universal health coverage service coverage index of the country or region, sex and age of the patient, study type, and diagnostic method. The pooled prevalence was estimated by a random-effect meta-analysis, and the significance of the associated factors was analysed by multivariable meta-regression. This study is registered with the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY), 2022100026. FINDINGS: Of the 56 967 records identified, 5236 were included in the quality assessment stage and 224 studies-from 71 countries or regions from all six WHO regions and including 2 979 179 individuals-were included in the final analysis. Significant heterogeneity was found between studies (I=99·9%). The estimated global prevalence of H pylori infection decreased from 58·2% (95% CI 50·7-65·8) in the 1980-90 period to 43·1% (40·3-45·9) in the 2011-22 period. Prevalence was relatively static between 1991 and 2010 but declined sharply between 2011 and 2022, with the largest decline in the WHO African region. Overall, a lower prevalence of H pylori infection was reported in younger people, high-income countries, or countries with high levels of universal health coverage, and by retrospective studies. Studies based on serological diagnostic methods generally reported higher H pylori prevalence than studies based on non-serological methods (53·2% [49·8-56·6] vs 41·1% [38·1-44·2]) and fluctuated less over time. INTERPRETATION: This meta-analysis shows a declining trend of H pylori prevalence globally, particularly in the 2011-22 period. These results could help to inform future health policy on prevention and management of this important infection. However, a considerable degree of heterogeneity exists between studies and further population-based epidemiological studies are needed. FUNDING: None.
2Prevalence of Helicobacter pylori infection in China: A systematic review and meta-analysis.PubMed
Shuai Ren, Pengpeng Cai, Yaqian Liu, et al.
J Gastroenterol Hepatol. 2022 Mar;37(3):464-470. doi: 10.1111/jgh.15751. Epub 2021 Dec 13.
BACKGROUND AND AIM: Helicobacter pylori (H. pylori) infection rates have been changing with different populations and geographic areas. We systematically evaluated the longitudinal trends in H. pylori prevalence in China over the past decades. METHODS: We performed a systematic review of literature reporting the prevalence of H. pylori infection in mainland China from 1990 to 2019 in the PubMed and China National Knowledge Infrastructure databases. We conducted a meta-analysis of qualified studies using a random effects model to estimate the pooled prevalence with a 95% confidence interval (95%CI). RESULTS: A total of 412 eligible studies with 1 377 349 subjects were included. The pooled H. pylori prevalence was 44.2% (95%CI: 43.0-45.5%) in mainland China, with an estimated 589 million individuals infected with H. pylori. The prevalence was relatively high in the Northwest (51.8%, 95%CI: 47.5-56.1%), East (47.7%, 95%CI: 45.4-50.0%), and Southwest China (46.6%, 95%CI: 42.1-51.1%). The prevalence significantly decreased from 58.3% (95%CI: 50.7-65.5%) in the period 1983-1994 to 40.0% (95%CI: 38.2-41.8%) in the period 2015-2019. The prevalence increased with age, ranging from 28.0% (95%CI: 23.9-32.5%) in children and adolescents to 46.1% (95%CI: 44.5-47.6%) in adults. CONCLUSION: Although the burden of H. pylori infections is still huge in China, the infection rate has been decreasing over the past decades. Targeted H. pylori eradication strategies may be considered in areas or populations with a high incidence of gastric cancer.
3The prevalence of Helicobacter pylori infection in the Peoples Republic of China.PubMed
Y Y Li, P J Hu, G G Du, et al.
Am J Gastroenterol. 1991 Apr;86(4):446-9.
Meta-analysis on data from 16 (two volunteer and 14 endoscopic) studies ahs been performed to investigate the prevalence of Helicobacter pylori infection in the stomachs of individuals within the Peoples Republic of China. In this survey covering 2216 cases (89 volunteers and 2127 endoscopy patients), the incidence of H. pylori infection in 15- to 22-yr-old healthy volunteers, and in 13- to 88-yr-old symptomatic patients undergoing gastroscopy was 49.4% and 64.5%, respectively. The frequency of H. pylori infection in chronic gastritis (63.6%), gastric ulcer (71.9%), and duodenal ulcer disease (73.1%) differed significantly from that in histologically normal individuals (8.2%), confirming the relationship of H. pylori infection with those disease states. We found no significant association between H. pylori infection and symptoms.
4Tracking the Helicobacter pylori Epidemic in Adults and Children in China.PubMed
Zixing Wang, Yaoda Hu, Ran Fei, et al.
Helicobacter. 2024 Sep-Oct;29(5):e13139. doi: 10.1111/hel.13139.
BACKGROUND: The Helicobacter pylori epidemic in China accounts for up to a third of gastric cancers worldwide. We aim to monitor the temporal and spatial dynamics of H. pylori infection in both adults and children across China. MATERIALS AND METHODS: We developed a surveillance system consisting of a data collection component that harnessed survey reports in natural populations and an analysis component that accounted for the differences in survey time and location, population age structure, and H. pylori detection method. System outputs were estimates of the prevalence of H. pylori in adults and children (aged ≤ 14 years) presented at three hierarchical levels (regional, provincial, and prefectural). RESULTS: The overall prevalence of H. pylori infection declined sharply in adults (63.3%, 52.5%, 43.4%, and 38.7%) and less sharply in children (23.1%, 26.1%, 16.0%, and 15.7%) in 1983-1999, 2000-2009, 2010-2014, and 2015-2019, respectively. The changes were asynchronous across regions, with the most marked declines in the Northwest, the Hong Kong-Macao-Taiwan region, and the East. We estimated that 457.6 million adults and 44.5 million children have been infected with H. pylori, with cross-province disparities in prevalence ranging from 24.3% to 69.3% among adults and 2.9% to 46.3% among children. In general, the risk level of gastric cancer increased as the prevalence of H. pylori increased. The correlation was statistically significant for both adult men (Spearman coefficient of correlation: 0.393, p = 0.0146) and women (0.470, p = 0.0029). CONCLUSIONS: The tracking system would be important for the continuous and stratified tracking of the Helicobacter pylori epidemic across China and can be used to furnish an evidence base for the formulation of tailored prevention strategies.
5Review: Epidemiology of Helicobacter pylori infection.PubMed
Mārcis Leja, Ieva Grinberga-Derica, Ceren Bilgilier, et al.
Helicobacter. 2019 Sep;24 Suppl 1:e12635. doi: 10.1111/hel.12635.
This review summarizes recent publications on the epidemiology of Helicobacter pylori. Two major systemic analyses, from Malaysia and Ethiopia, were published. The Brazilian Consensus Conference has stated that H pylori infection is an infectious disease with an indication for antimicrobial therapy. A continuous decrease in H pylori prevalence was reported from many regions worldwide, including Korea, China, Iran, and Austria. A cross-sectional H pylori prevalence study conducted in the United Arab Emirates found 41% prevalence in a group of healthy children and adults. Several studies from Asia addressed H pylori prevalence in adults undergoing regular checkup. The largest of such studies, performed in Korea, involved 24 471 subjects and reported 41.5% seroprevalence. A relatively smaller study from East China on 3252 subjects reported 27.5% prevalence. In contrast, a study from Spain reported 87.2% seroprevalence. A report on the association between smoking and H pylori seropositivity was published on behalf of the Stomach Cancer Pooling (StoP) Project-a consortium of epidemiological studies of gastric cancer. Also, other potential risk factors, including occupational risk factors, water supply, and food were analyzed. Gastroesophageal reflux and sexual partners has been associated with a higher risk for H pylori acquisition, and gut microbiota was suggested to play a role in intrafamilial transmission of H pylori. Finally, in a few studies (from Mexico and Japan), the catalytic model for predicting the potential risk of acquiring H pylori infection in the future was used. As anticipated, a further decline in H pylori-related disease was demonstrated by applying the modeling.
6Prevalence of infection in China from 2014-2023: A systematic review and meta-analysis.PubMed
Lu Xie, Guang-Wei Liu, Ya-Nan Liu, et al.
World J Gastroenterol. 2024 Nov 21;30(43):4636-4656. doi: 10.3748/wjg.v30.i43.4636.
BACKGROUND: stands as the predominant infectious agent linked to the onset of gastritis, peptic ulcer diseases, and gastric cancer (GC). Identified as the exclusive bacterial factor associated with the onset of GC, it is classified as a group 1 carcinogen by the World Health Organization. The elimination of plays a crucial role in the primary prevention of GC. While the prevalence has declined in recent decades, infection is still highly prevalent in China, accounting for a significant part of the disease burden of GC. Therefore, updated prevalence information for infection, especially regional and demographic variations in China, is an important basis for the design of targeted strategies that will be effective for the prevention of GC and application of policies for control. AIM: To methodically evaluate the occurrence of infection throughout China and establish a reference point for subsequent investigations. METHODS: A systematic review and meta-analysis was conducted following established guidelines, as detailed in our methodology section. RESULTS: Our review synthesized data from 152 studies, covering a sample of 763827 individuals, 314423 of whom were infected with . We evaluated infection rates in mainland China and the combined prevalence of was 42.8% (95%CI: 40.7-44.9). Subgroup analysis indicated the highest prevalence in Northwest China at 51.3% (95%CI: 45.6-56.9), and in Qinghai Province, the prevalence reached 60.2% (95%CI: 46.5-73.9). The urea breath test, which recorded the highest infection rate, showed a prevalence of 43.7% (95%CI: 41.4-46.0). No notable differences in infection rates were observed between genders. Notably, the prevalence among the elderly was significantly higher at 44.5% (95%CI: 41.9-47.1), compared to children, who showed a prevalence of 27.5% (95%CI: 19.58-34.7). CONCLUSION: Between 2014 and 2023, the prevalence of infection in China decreased to 42.8%, down from the previous decade. However, the infection rates vary considerably across different geographical areas, among various populations, and by detection methods employed.
7Prevalence of common upper gastrointestinal diseases in Chinese adults aged 18-64 years.PubMed
Hong Yang, Mei Zhang, Hui Li, et al.
Sci Bull (Beijing). 2024 Dec 30;69(24):3889-3898. doi: 10.1016/j.scib.2024.07.048. Epub 2024 Nov 5.
To investigate the prevalence of gastroesophageal reflux disease (GERD), reflux esophagitis (RE), digestive ulcer gastric ulcer (GU), duodenal ulcer (DU), and Helicobacter pylori infection in Chinese adults aged 18-64 years and their associated factors, a community-based cross-sectional study using a stratified multistage sampling method was conducted. A standardized questionnaire survey, the C-urea breath test, and gastroscopy were performed. Weighted methods were used to estimate the prevalence of diseases or infection mentioned above and their risk factors. Finally, 27,637 participants aged 18-64 years were enrolled from 2017 to 2018. The prevalence (95% confidence interval) of GERD, RE, GU, DU, and H. pylori infection was estimated to be 10.5% (7.8%-14.2%), 5.4% (3.9%-7.3%), 2.5% (1.7%-3.7%), 4.5% (3.6%-5.4%), and 41.5% (36.7%-46.4%), respectively. The fraction of H. pylori infection reached 58.6% and 61.1% among the GU and DU patients, respectively. Weighted multivariable logistic regression models showed that GERD, RE, and GU shared the common risk factors of age and obesity. Dose-response relationships were observed between smoking and all four diseases, as well as alcohol consumption and GERD and H. pylori infection. Northwest China had the highest prevalence of GERD (23.9%), RE (8.7%), GU (7.8%), DU (7.3%), and H. pylori infection (63.6%); however, the southwest region had the highest prevalence of GU but the lowest of DU, RE, and H. pylori infection. Non-steroidal anti-inflammatory drugs were positively associated with GERD risk. On the contrary, a reduced risk of GU was observed among H. pylori-infected patients taking this drug. In summary, the prevalence of GERD, RE, and H. pylori infection still appears high in China. H. pylori infection eradication remains the priority to reduce the burden of peptic ulcer disease. The aging population, high prevalence of overweight or obesity, smoking, and drinking in China could explain the high burden of these diseases, thus suggesting the targeted preventive measures for upper gastrointestinal diseases in the future.
8[Prevalence of infection and risk factors among family members in Qinghai Province, China].PubMed
C X Li, X H Wang, Z Q Ma, et al.
Zhonghua Nei Ke Za Zhi. 2024 Jan 1;63(1):41-45. doi: 10.3760/cma.j.cn112138-112138-20231028-00259.
To investigate the prevalence of infection among family members, and analyze associated risk factors. The current investigation was a cross-sectional study. The Qinghai region was stratified into urban areas, agricultural areas, and pastoral areas. The urban areas of Xining City, the agricultural areas of Haidong City, and the pastoral areas of Haibei Tibetan Autonomous Prefecture were selected. A total of 396 resident families (1 131 people) who underwent health checkups from 2021 to 2022 in the above areas were included in the survey study. Questionnaires were administered and infection was detected using the C-urea breath test. Numerical data were expressed as cases and percentages, and the Chi-square test was used to compare differences in infection rates in the populations and families in each group. Multifactorial logistic regression was used to analyze risk factors for infection, and 0.05 was considered statistically significant. The prevalence of infection in Qinghai province was 52.8% (597/1 131) and the prevalence of infection in households was 80.6% (319/396). In -positive households with at least 1 infected spouse, 40.4% (36/89) had only 1 infected spouse, and in 59.6% (53/89) both spouses were infected. In analysis of children infected by parents with , 20.0% (9/45) of households had fathers and children infected, 48.9% (22/45) had mothers and children infected, and 31.1% (14/45) had both parents and children infected. In univariate analysis there was a statistically significant difference in the overall comparison of infection rates among families with different numbers of people living together (=11.12, =0.004), and between-group comparisons suggested that infection rates were higher in families with 4 or 5 people and more than 5 people living together than in families with 2 or 3 people living together. The infection rate was higher in families that did not use serving chopsticks and spoons during family meals than in families that did use serving chopsticks and spoons (=6.12, =0.013). In multifactorial logistic regression analyses the number of people living together in a family and whether or not serving chopsticks and spoons were used at family meals were associated with infection (<0.05). The infection rate in families in Qinghai Province is high, and there is a clear association with family aggregation. It is more common for both members of a couple to be infected, and infection of a mother has a greater effect on the children's infection status than infection of a father. The infection rate of was lower in families that used serving chopsticks and spoons during dinner gatherings, and the fewer the number of people living together in the family, the lower the infection rate.
9Impact of high-altitude hypoxia on Helicobacter pylori-induced gastritis pathological manifestations and inflammatory responses.PubMed
Chunxia Li, Xuehong Wang, Sen Cui
J Physiol Anthropol. 2024 Jul 5;43(1):17. doi: 10.1186/s40101-024-00364-5.
BACKGROUND: Chronic gastritis caused by Helicobacter pylori (Hp) infection is a common gastrointestinal disorder. Despite the high prevalence of Hp infection and chronic gastritis in the Tibetan Plateau, there is a lack of studies elucidating the influence of plateau hypoxia on Hp-induced gastritis. This study aimed to investigate the impact of high-altitude hypoxia on Hp-induced gastritis, particularly focusing on pathological manifestations and inflammatory responses. METHODS: This study was conducted from July 2023 to March 2024 at the Department of Gastroenterology, Affiliated Hospital of Qinghai University. Ninety patients diagnosed with chronic gastritis were enrolled in the study and divided into four groups based on their residential altitude and Hp infection status. Data on endoscopic and pathological characteristics were collected, along with serum oxidative stress and inflammatory markers. RESULTS: Patients with Hp gastritis exhibit distinctive features in the gastric mucosa, including diffuse erythema, enlarged folds, and white turbid mucus during endoscopy. Notably, individuals with Hp gastritis at high altitudes show a higher prevalence of diffuse erythema and enlarged folds. Pathological analysis reveals that these patients have elevated gastric mucosal inflammation scores and increased chronic and active inflammation. Furthermore, individuals with Hp gastritis at high altitudes demonstrate elevated levels of serum TNF-α, IL-1β, IL-6, and MDA, as well as reduced serum SOD and GSH-Px activities. CONCLUSIONS: High-altitude hypoxia may exacerbate gastric mucosal damage by enhancing oxidative stress and inflammatory response induced by Hp infection.
10Spatial-temporal Distribution and Influencing Factors of Helicobacter pylori Infection in Chinese Mainland, 2001-2020: A Systematic Review and Meta-Analysis.PubMed
Tai-Liang Lu, Jia-Min Zhang, Shao-Rong Li, et al.
J Clin Gastroenterol. 2022;56(5):e273-e282. doi: 10.1097/MCG.0000000000001691.
BACKGROUND: The spatial-temporal distribution of Helicobacter pylori infection in China is poorly understood. We aimed to study the spatial-temporal distribution of H. pylori infection in Chinese mainland and to explore its influencing factors. MATERIALS AND METHODS: We searched the relevant literature from 2001 to 2021 and applied meta-analysis to obtain the pooled prevalence estimates of all studies and subgroups. Then, we used the pooled prevalence as the dependent variable for the following analysis, including time series analysis, statistical mapping, spatial autocorrelation analysis, and influencing factor analysis based on generalized additive model and panel data model. RESULTS: A total of 726 articles and 3,407,392 people were included. The pooled prevalence was 43.7% (95% confidence interval: 42.7%-44.8%). The prevalence decreased in the past 20 years, with high in the eastern and western regions and low in the central region. Qinghai Tibet Plateau and Guizhou Plateau were the high incidence areas of this disease. The intake of vegetable oil, aquatic products, meat, milk, per capita gross domestic product, and annual average humidity were significantly correlated with H. pylori. CONCLUSIONS: The prevalence of H. pylori is decreasing in Chinese mainland, but still high in underdeveloped areas. Appropriate strategies for the prevention need greater attention.
11Large-scale, national, family-based epidemiological study on infection in China: the time to change practice for related disease prevention.PubMed
Xian-Zhu Zhou, Nong-Hua Lyu, Hui-Yun Zhu, et al.
Gut. 2023 May;72(5):855-869. doi: 10.1136/gutjnl-2022-328965. Epub 2023 Jan 23.
BACKGROUND AND AIMS: Current practice on infection mostly focuses on individual-based care in the community, but family-based management has recently been suggested as a better strategy for infection control. However, the family-based infection status, risk factors and transmission pattern remain to be elucidated. METHODS: From September 2021 to December 2021, 10 735 families (31 098 individuals) were enrolled from 29 of 31 provinces in mainland China to examine family-based infection, related factors and transmission pattern. All family members were required to answer questionnaires and test for infection. RESULTS: Among all participants, the average individual-based infection rate was 40.66%, with 43.45% for adults and 20.55% for children and adolescents. Family-based infection rates ranged from 50.27% to 85.06% among the 29 provinces, with an average rate of 71.21%. In 28.87% (3099/10 735) of enrolled families, there were no infections; the remaining 71.13% (7636/10 735) of families had 1-7 infected members, and in 19.70% (1504/7636), all members were infected. Among 7961 enrolled couples, 33.21% had no infection, but in 22.99%, both were infected. Childhood infection was significantly associated with parental infection. Independent risk factors for household infection were infected family members (eg, five infected members: OR 2.72, 95% CI 1.86 to 4.00), living in highly infected areas (eg, northwest China: OR 1.83, 95% CI 1.57 to 2.13), and large families in a household (eg, family of three: OR 1.97, 95% CI 1.76 to 2.21). However, family members with higher education and income levels (OR 0.85, 95% CI 0.79 to 0.91), using serving spoons or chopsticks, more generations in a household (eg, three generations: OR 0.79, 95% CI 0.68 to 0.92), and who were younger (OR 0.57, 95% CI 0.46 to 0.70) had lower infection rates (p<0.05). CONCLUSION: Familial infection rate is high in general household in China. Exposure to infected family members is likely the major source of its spread. These results provide supporting evidence for the strategic changes from individual-based treatment to family-based management, and the notion has important clinical and public health implications for infection control and related disease prevention.
12Helicobacter pylori infection may be implicated in the topography and geographic variation of upper gastrointestinal cancers in the Taihang Mountain high-risk region in northern China.PubMed
Denggui Wen, Nan Zhang, Baoen Shan, et al.
Helicobacter. 2010 Oct;15(5):416-21. doi: 10.1111/j.1523-5378.2010.00790.x.
BACKGROUNDS: Helicobacter pylori infection is prevalent in China. Chronic infection of the bacterial not only causes distal stomach cancer, but also confers risk to gastric cardia adenocarcinoma. Because H. pylori infection is inversely associated with esophageal adenocarcinoma, globally the infection rate is significantly correlated with the ratio of squamous carcinoma to adenocarcinoma of the esophagus. These agree with the topography of upper gastrointestinal cancer observed in the Taihang Mountain high-risk region where both gastric cardia and non-cardia adenocarcinoma coincide with esophageal squamous cancer, but with almost no distal esophageal adenocarcinoma. Moreover, as altitude increases from plain to mountains, we observed progressively increasing incidence rates of gastric adenocarcinomas in recent years in the region. Because H. pylori infection is a definite carcinogen to gastric adenocarcinoma and is more prevalent in the mountain than in plain areas due to undeveloped living conditions, the observation gives the impression as though H. pylori infection is implicated. AIMS: This article aims to note the role of H. pylori infection in upper gastrointestinal cancer in the Taihang Mountain high-risk region in northern China. MATERIALS AND METHODS: First the unique topography and geographic variation of upper gastrointestinal cancer in the region is described to indicate a possible role of H. pylori infection, then we review studies on prevalence of H. pylori infection in the high-risk region and describe difference in socioeconomic development and water hygiene between the plains and the mountains as related to the prevalence of H. pylori infection. RESULTS: Coincidence of gastric cancer in the region and a progressively increasing rate of the cancer from the plain towards the mountains indicate H. pylori infection may be implicated in upper gastrointestinal cancer. CONCLUSION: International collaboration is needed to study H. pylori and upper gastrointestinal cancer in the region when rapid industrialization is just beginning.
13Distribution of Helicobacter pylori in north China.PubMed
Yue-Hua Gong, Ying Wang, Yuan Yuan
World J Gastroenterol. 2005 Jun 21;11(23):3523-7. doi: 10.3748/wjg.v11.i23.3523.
AIM: To compare the distribution of virulence-associated genotypes of Helicobacter pylori (H pylori) in two areas of north China with different gastric cancer risk and furthermore probe into the pathogenicity of the bacterium. METHODS: Gastric biopsies were taken from 355 subjects from Zhuanghe, a high risk area of gastric cancer, and 136 subjects from Shenyang, a low risk area of gastric cancer. A total of 149 H pylori strains isolated from these patients were studied by PCR for differences in the genotypes of cagA, vacA, and iceA. RESULTS: In patients with high risk for gastric cancer, higher frequencies of vacA s1 or s1m1b genotypes were found as compared to those from the low risk area. CONCLUSION: There is significantly different distribution of H pylori genotypes between Zhuanghe and Shenyang areas in north China.
14Prevalence Difference of Infection Between Tibetan and Han Ethnics in China: A Meta-analysis on Epidemiologic Studies (SIGES).PubMed
Dan Bai, Kai Liu, Rui Wang, et al.
Asia Pac J Public Health. 2023 Mar;35(2-3):103-111. doi: 10.1177/10105395221134651. Epub 2022 Nov 2.
China is a multi-ethnic country, and the prevalence of () infection may be diverse among ethnics. This meta-analysis was conducted to compare the prevalence of infection between Tibetans and Han ethnics. Ten studies that reported the prevalence of infection between Tibetans and Hans in China were eligible. The pooled prevalence of infection was 62.2% versus 55.3% among Tibetans and Hans, respectively. Tibetans had a higher risk of infection than Hans (odds ratio [OR] = 1.38). In subgroup analysis, Tibetans with upper gastrointestinal symptoms (OR = 1.51), inhabiting in Tibet (OR = 1.51), or inhabiting in Northwestern region (OR = 1.15) had significantly higher risks of infection. In addition, in the recent 10 years, Hans showed a decreased risk of infection (OR = 1.81). Heterogeneity was common, while sensitivity analyses showed partially inconsistent results against main findings. This study demonstrated higher prevalence of infection in Tibetans compared with Hans, especially in recent years, or in Tibet and northwest China, as well as symptomatic Tibetans. The results suggest tailored strategy and robustness need to be further considered for screening and eradication among Tibetans.
15Systematic review of the relationship of Helicobacter pylori infection with geographical latitude, average annual temperature and average daily sunshine.PubMed
Chao Lu, Ye Yu, Lan Li, et al.
BMC Gastroenterol. 2018 Apr 17;18(1):50. doi: 10.1186/s12876-018-0779-x.
BACKGROUND: Helicobacter pylori (H. pylori) infection is a worldwide threat to human health with high prevalence. In this study, we analyzed the relationship between latitude, average annual temperature, average daily sunshine time and H. pylori infection. METHODS: The PubMed, ClinicalTrials.gov , EBSCO and Web of Science databases were searched to identify studies reporting H. pylori infection. Latitude 30° was the cut-off level for low and mid-latitude areas. We obtained information for latitude, average annual temperature, average daily sunshine, and Human Development Index (HDI) from reports of studies of the relationships with H. pylori infection. RESULTS: Of the 51 studies included, there was significant difference in H. pylori infection between the low- and mid-latitude areas (P = 0.05). There was no significant difference in the prevalence of H. pylori infection in each 15°-latitude zone analyzed (P = 0.061). Subgroup analysis revealed the highest and lowest H. pylori infection rates in the developing regions at > 30° latitude subgroup and the developed regions at < 30° latitude subgroup, respectively (P < 0.001). Multivariate analysis showed that average annual temperature, average daily sunshine time and HDI were significantly correlated with H. pylori infection (P = 0.009, P < 0.001, P < 0.001), while there was no correlation between H. pylori infection and latitude. CONCLUSIONS: Our analysis showed that higher average annual temperature was associated with lower H. pylori infection rates, while average daily sunshine time correlated positively with H. pylori infection. HDI was also found to be a significant factor, with higher HDI associated with lower infection rates. These findings provide evidence that can be used to devise strategies for the prevention and control of H. pylori.
16The global prevalence of and factors associated with Helicobacter pylori infection in children: a systematic review and meta-analysis.PubMed
Changzheng Yuan, Davies Adeloye, Tzu Tsun Luk, et al.
Lancet Child Adolesc Health. 2022 Mar;6(3):185-194. doi: 10.1016/S2352-4642(21)00400-4. Epub 2022 Jan 25.
BACKGROUND: Synthesised data on the prevalence of, and factors associated with, paediatric Helicobacter pylori infection at the global level remain scarce. We aimed to estimate the global prevalence of H pylori infection and its associated factors in children and adolescents. METHODS: In this systematic review and meta-analysis, we searched PubMed, Embase, MEDLINE, and Scopus for observational population-based studies published between database inception and Oct 25, 2021, without language or geographical restrictions. We included studies that reported the prevalence of H pylori infection in children aged 18 years or younger. Records were screened and data were extracted using a standardised extraction form. We estimated the worldwide prevalence of H pylori infection in children (our main outcome) using multilevel mixed-effects meta-regression and then stratified prevalence by diagnostic method (serology vs urea breath tests or stool antigen tests). We analysed the significance of associated factors using a random-effects meta-analysis. This study is registered in PROSPERO, CRD42020209717. FINDINGS: We identified 3181 records, of which 198 articles with 632 data points from 152 650 children were included. The overall global prevalence of H pylori infection in children was 32·3% (95% CI 27·3-37·8), which varied by diagnostic test (28·6% [23·0-35·0] for serology vs 35·9% [29·2-43·2] for urea breath tests or stool antigen tests). Regardless of diagnostic test, the prevalence of H pylori infection was significantly higher in low-income and middle-income countries than in high-income countries (43·2% [36·5-50·2] vs 21·7% [16·9-27·4]; p<0·0001) and in older children than in younger children (41·6% [35·6-47·8] in 13-18-year-olds vs 33·9% [28·6-39·7] in 7-12-year-olds vs 26·0% [21·4-31·0] in 0-6-year-olds; p<0·0001). Paediatric H pylori infection was significantly associated with lower economic status (odds ratio [OR] 1·63 [95% CI 1·46-1·82]), more siblings or children (1·84 [1·44-2·36]), room sharing (1·89 [1·49-2·40]), no access to a sewage system (1·60 [1·22-2·10]), having a mother infected with H pylori (3·31 [2·21-4·98]), having a sibling or siblings infected with H pylori (3·33 [1·53-7·26]), drinking unboiled or non-treated water (1·52 [1·32-1·76]), and older age (OR per year 1·27 [1·15-1·40]). INTERPRETATION: H pylori infection is still highly prevalent in children and adolescents globally. Our findings can help to guide further research and the development and implementation of preventive and therapeutic measures to reduce H pylori infection in children. FUNDING: None.
17Sex differences in Helicobacter pylori infection and recurrence rate among 81,754 Chinese adults: a cross-sectional study.PubMed
Yuqin Qiao, Yun Zhou, Li Zhao, et al.
BMC Gastroenterol. 2024 Sep 11;24(1):305. doi: 10.1186/s12876-024-03404-7.
OBJECTIVE: To compare the sex differences of Helicobacter pylori (HP) infection rate and 1-year recurrence rate. METHODS: A cross-sectional study was conducted on the prevalence of HP infection in 81,754 people who underwent physical examination in physical examination centers and outpatient clinics of the Affiliated Hospital of Gansu University of Traditional Chinese Medicine, the Second People's Hospital of Zhangye City, Tianshui City Hospital of Integrated Chinese and Western Medicine, the First and Second Department of The First Hospital of Lanzhou University Physical Examination Center, from March 2010 to December 2019. Among them, 53,771 (65.77%) were males (18-91 years old) and 27,983 (34.23%) were females (18-94 years old). According to age, they were divided into young group, middle-aged group and old group. 1448 asymptomatic infected patients were selected and treated with bismuth-containing quadruple drug eradication therapy for 2 weeks. The eradication rate and recurrence rate after 1 year were compared between males and females. RESULTS: The overall infection rate was 49.59%, including 49.74% in males and 49.3% in females. The risk of infection in young women was lower than that in men (OR = 0.908, 95%CI: 0.868-0.95, P < 0.01), the risk of infection in older women was higher than that in men (OR = 1.137, 95%CI: 1.041-1.243, P < 0.01). The female infection rate was positively correlated with age from 18 to 60, and Spearman's correlation coefficient was 0.825 (P < 0.01). The overall eradication rate was 84.67% in intention-to-treat analysis (ITT) and 88.46% in protocol analysis (PP). The eradication rates of ITT and PP in the older group were 78.38% and 82.27%, respectively, which were lower than 87.25% and 89.39% in the male group (P < 0.05). The 1-year overall recurrence rate was 3.86%, including 2.82% in males and 5.44% in females (P < 0.05), female was a risk factor for recurrence after eradication after controlling for age (OR = 2.177, 95%CI 1.166-4.066, P < 0.05). There were no obvious adverse reactions during the treatment. CONCLUSION: There is a positive linear correlation between HP infection rate and age increase in women. Older women have the characteristics of high HP infection rate, low eradication rate and high recurrence rate.
18Sex-Specific Risk Factors Associated with Infection Among Individuals Undergoing Health Examinations in China.PubMed
Yumei Wu, Hui Zeng, Meiping Zhang, et al.
Int J Gen Med. 2022 Jun 29;15:5861-5868. doi: 10.2147/IJGM.S367142. eCollection 2022.
PURPOSE: is one of the most common causes of peptic ulcers, gastritis, and gastric cancers. This study investigated sex-specific differences in the prevalence of infection and its associated factors among individuals undergoing hospital-based health examinations in southern China. METHODS: This study enrolled consecutive healthy individuals who underwent regular health examinations at a hospital physical examination center between September 2020 and September 2021. Anthropometric characteristics and biochemical profiles were measured. All individuals underwent carbon-13 urea breath tests. Univariate and multivariate analyses were used to evaluate the factors associated with infection. RESULTS: A total of 5035 individuals (men, 59.1%; women, 40.9%) were included in the analyses. The total rate of infection was 35.0% (men, 35.5%; women, 34.3%). In the multivariate analysis, the risk factors identified for infections were high fasting blood glucose levels and blood pressure ≥160 mmHg in men and older age, high body mass index, and low albumin levels in women. CONCLUSION: These findings suggest that physicians must be aware of the metabolic factors associated with infections in the Chinese population. Early detection of these factors and timely intervention are expected to reduce infections and provide a theoretical basis for the primary prevention of several gastrointestinal diseases.
19Further evidence of ethnic and gender differences for Helicobacter pylori infection among endoscoped patients.PubMed
S Sasidharan, A M Uyub, A A Azlan
Trans R Soc Trop Med Hyg. 2008 Dec;102(12):1226-32. doi: 10.1016/j.trstmh.2008.05.006. Epub 2008 Jun 30.
HeIicobacter pylori infection rate was determined in 697 consecutive patients with ulcer, gastritis, duodenitis and non-ulcer dyspepsia by endoscopy at a Malaysian hospital in 1999-2002. Biopsies of the gastric antrum and body were subjected to the urease test, Gram staining of impression smears and culture examination. Infection was defined as a positive result in at least one test. The infection rates were 32.1, 10.4, 20.0 and 16.2% in ulcer, gastritis, duodenitis and non-ulcer dyspepsia patients, respectively. Overall, the prevalence of H. pylori infection was 14.6%, with the rate among the Indian (21.7%), Chinese (19.2%) and Bangladeshi foreign worker (23.1%) groups significantly higher (P<0.05) than that of the Malays (5.8%). Generally, the prevalence rate among males (18.9%) was significantly higher (P<0.001) than that among females (9.0%), but for a particular ethnic group, such trend and significant differences (P<0.05) were observed only among the Malays. In terms of gender, the prevalence rates of Malay males and females were also significantly lower (P<0.05) than those of Chinese and Indians. In conclusion, there is a significant difference in H. pylori infection prevalence rates among ethnic groups (highest in Indians, then Chinese and unusually low in Malays) and gender groups (highest in males) in Malaysia.
20Prevalence and risk factors of infection in military personnel: a systematic review and meta-analysis.PubMed
Chunmei Wang, Jun Liu, Yang An, et al.
Indian J Pathol Microbiol. 2022 Jan-Mar;65(1):23-28. doi: 10.4103/IJPM.IJPM_1084_20.
BACKGROUND AND AIMS: Helicobacter pylori infection is prevalent and recognized as a major cause of gastrointestinal diseases in the world. Previous studies on the prevalence of H. pylori infection in military personnel have shown some conflicting results. This study aimed to estimate the pooled prevalence of H. pylori infection and evaluate its risk factors in military personnel. METHODS: The PubMed, EMBASE, and Cochrane Library databases were searched. We pooled the prevalence of H. pylori infection in military personnel using a random-effect model. Metaregression analysis was used to explore the sources of heterogeneity. Pooled proportion of H. pylori infection with 95% confidence interval (CI) was calculated. RESULTS: Sixteen studies were included. Meta-analysis showed that the overall prevalence of H. pylori infection was 32% (95% CI = 31-33) in military personnel. There was a significant heterogeneity. Metaregression analysis showed that study region (P = 0.0004) and publication year (P = 0.023) were the potential sources of heterogeneity. In the subgroup analysis by study region, the highest prevalence was found in Asia (50.2%; 95% CI = 49-51.4). In the subgroup analysis by diagnostic methods for H. pylori, the highest prevalence was found when urea breath test was employed (47.9%; 95% CI = 46.5-49.3). The most common risk factor for H. pylori infection was familial aggregation, followed by living environment and age. CONCLUSION: H. pylori infection is common in military personnel. In future, we may require appropriate population screening for H. pylori infection by multiple diagnostic tests and increase the knowledge and awareness of the bacterial transmission among military personnel.
21Potential of traditional Chinese medicine in managing and preventing infection in Chinese military.PubMed
Hengrui Liu, Ren-Jun Gu, Chen Li, et al.
World J Gastroenterol. 2025 May 14;31(18):103754. doi: 10.3748/wjg.v31.i18.103754.
() infection is prevalent among Chinese military personnel, with regional rates exceeding 40%, and is a well-established risk factor for gastric cancer. Addressing this infection is vital for improving soldiers' health and operational readiness while reducing the long-term healthcare burden. This commentary explores the feasibility and advantages of incorporating traditional Chinese medicine (TCM) into strategies for managing and preventing infections within the military. TCM offers a multi-target mechanism that not only combats bacterial infections but also enhances gastrointestinal health and boosts immunity, making it particularly effective in high-stress environments like the military. Unlike antibiotics, TCM is less likely to induce resistance even with large-scale use, providing a sustainable treatment option. Its affordability and cultural acceptance among Chinese personnel further enhance its feasibility. Additionally, TCM's history in military medicine supports its credibility, and its flexibility allows for personalized treatment tailored to individual soldiers' needs. TCM's convenient storage and deployment make it ideal for remote and challenging environments. Integrating TCM into military healthcare systems could provide a holistic, cost-effective, and sustainable approach to managing infections, reducing prevalence and associated risks such as gastric cancer. Future research and pilot programs are essential to validate TCM's effectiveness and implementation in military settings.
22[Risk factors associated with Helicobacter pylori infection in army and navy recruits].PubMed
Jianwei Yu, Hejuan An, Hui Su, et al.
Zhonghua Yi Xue Za Zhi. 2015 Jan 13;95(2):138-41.
OBJECTIVE: To explore the Helicobacter pylori (Hp) infection rate among army and navy recruits, examine its associated risk factors and provide theoretic rationales for Hp control. METHODS: A cross-sectionalstudy was performed for 1 732 subjects (aged 17-24 years) selected from 18 new recruit populations in Inner Mongolia and Zhoushan area from September 2013 to November 2013.Hp infection was detected by (13)C-urea breath test. Meanwhile, a questionnaire containing 62 potential factors related to Hp infection was surveyed. In addition, (13)C-urea breath test was performed in 513 navy veterans (aged 19-51 years) in Zhoushan area from April 2013 to October 2013. The data of risk factors were analyzed by χ(2) test and multivariate Logistic regression. RESULTS: A total of 2 162 soldiers were enrolled and 1 649 new recruits completed two surveys. The overall Hp infection rate was 46.5% (768/1 649), which is lower than the previous studies (52.9%). And it was 47.0% (377/802) in army new recruits and 46.0% (390/847) in navy new recruits. For new recruits, Hp infection was associated with number of family members, washing tableware with detergents, first drinking age and paring fruits before eating (all P < 0.05). However, there was no association with age, education level or washing hands before meal (all P > 0.05). The Hp infection rate was higher in recruits from the West China and North China.In addition, the infection rate was 60.8% (312/513) in a population of 513 veterans. It was 46.6% (768/1 649) in recruits less than onemonth of service, 59.2% (180/304) in recruits less than two years of service and 63.2% (132/209) in recruits more than two years of service, the difference had statistical significance(P < 0.05). Logistic analysis of multiple variables showed that number of family members, washing tableware with detergents, first drinking age and paring fruits before eating were independent risk factors (OR = 1.574, 0.538, 0.638, 0.855; 95%CI:1.077-2.301, 0.362-0.798, 0.486-0.837, 0.457-0.961). CONCLUSIONS: The Hp infection rate is similar between army and navy recruits. It has dropped significantly and its epidemic region changed in new male recruits compared to a decade ago in china. Hp infection clustered within families. The factors including fewer family members, washing tableware without detergents, first drinking at young age and no paring fruits before eating are risk factors of Hpinfection. And a longer service time is associated with higher Hp infection rate in recruits.
23Biofilm and Helicobacter pylori: from environment to human host.PubMed
Apolinaria García, María José Salas-Jara, Carolina Herrera, et al.
World J Gastroenterol. 2014 May 21;20(19):5632-8. doi: 10.3748/wjg.v20.i19.5632.
Helicobacter pylori (H. pylori) is a Gram negative pathogen that selectively colonizes the human gastric epithelium. Over 50% of the world population is infected with H. pylori reaching up to 90% of infected individuals in developing countries. Nonetheless the increased impact upon public health care, its reservoir and the transmission pathway of the species has not been clearly established yet. Molecular studies allowed the detection of H. pylori in various aquatic environments, even forming biofilm in tap water distribution systems in several countries, suggesting a role of water as a possible reservoir of the pathogen. The persistence of human infection with H. pylori and the resistance of clinical isolates to commonly used antibiotics in eradication therapy have been related to the genetic variability of the species and its ability to develop biofilm, demonstrated both in vivo and in vitro experiments. Thus, during the last years, experimental work with this pathogen has been focused in the search for biofilm inhibitors and biofilm destabilizing agents. However, only two anti- H. pylori biofilm disrupting agents have been successfully used: Curcumin - a natural dye - and N-acetyl cysteine - a mucolytic agent used in respiratory diseases. The main goal of this review was to discuss the evidences available in the literature supporting the ability of H. pylori to form biofilm upon various surfaces in aquatic environments, both in vivo and in vitro. The results published and our own observations suggest that the ability of H. pylori to form biofilm may be important for surviving under stress conditions or in the spread of the infection among humans, mainly through natural water sources and water distribution systems.
24Helicobacter pylori-induced gastric inflammation and gastric cancer.PubMed
Fei Wang, Wenbo Meng, Bingyuan Wang, et al.
Cancer Lett. 2014 Apr 10;345(2):196-202. doi: 10.1016/j.canlet.2013.08.016. Epub 2013 Aug 24.
Helicobacter pylori (H. pylori) infect over half of the world's population. The prevalence of H. pylori infection and the predominant genotype of H. pylori virulence factors vary considerably across different geographical regions. H. pylori could uniquely persist for decades in the harsh stomach environment, where it damages the gastric mucosa and changes the pattern of gastric hormone release, thereby affects gastric physiology. By utilizing various virulence factors, H. pylori targets different cellular proteins to modulate the host inflammatory response and initiate multiple "hits" on the gastric mucosa, resulting in chronic gastritis and peptic ulceration. Among the long-term consequences of H. pylori infection is gastric malignancies, particularly gastric cancer (GC) and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. As such, H. pylori has been recognized as a class I carcinogen by the International Agency for Research on Cancer. Despite a close causal link between H. pylori infection and the development of gastric malignancies, the precise mechanisms involved in this process are still obscure. Studies over the past two decades have revealed that H. pylori exert oncogenic effects on gastric mucosa through a complex interaction between bacterial factors, host factors, and environmental factors. Numerous signaling pathways can be activated by H. pylori. In this review, we aim to elaborate on the recent developments in the pathophysiological mechanisms of H. pylori-induced gastric inflammation and gastric cancer.
25Oncogenicity: Mechanism, Prevention, and Risk Factors.PubMed
Muzaheed
ScientificWorldJournal. 2020 Jul 12;2020:3018326. doi: 10.1155/2020/3018326. eCollection 2020.
(. ) is the most common cause of gastric ulcer; however, its association with gastric cancer has been proved through a variety of studies. Importantly, . infection affects around half of the world's population leading to a variety of gastric problems and is mostly present in asymptomatic form. Although about 20% of people infected with . develop preneoplastic gastric lesions in later stages of their life, around 2% of infected individuals develop gastric cancer. Nevertheless, the outcome of . infection is determined by complex interaction between the host genetics, its environment, and virulence factors of infecting strain. There are several biomarkers/traits of . that have been linked with the onset of cancer. Among these, presence of certain major virulence factors including cytotoxin-associated gene A (CagA), vacuolating cytotoxin (VacA), and outer inflammatory protein A (OipA) plays a significant role in triggering gastric cancer. These factors of . make it a potent carcinogen. Therefore, eradication of . infection has shown positive effects on decreasing the risk of gastric cancer, but this has become a challenge due to the development of antibiotic resistance in . against the antibiotics of choice. Thus, the unmet need is to develop new and effective treatments for . infection, considering the antimicrobial resistance in different regions of the world. This review discusses the properties of . associated with increased risk of gastric cancer, antibiotic resistance pattern, and the possible role of eradication of . in preventing gastric cancer.
26Helicobacter pylori and gastric cancer: mechanisms and new perspectives.PubMed
Yantao Duan, Yonghu Xu, Yi Dou, et al.
J Hematol Oncol. 2025 Jan 23;18(1):10. doi: 10.1186/s13045-024-01654-2.
Gastric cancer remains a significant global health challenge, with Helicobacter pylori (H. pylori) recognized as a major etiological agent, affecting an estimated 50% of the world's population. There has been a rapidly expanding knowledge of the molecular and pathogenetic mechanisms of H. pylori over the decades. This review summarizes the latest research advances to elucidate the molecular mechanisms underlying the H. pylori infection in gastric carcinogenesis. Our investigation of the molecular mechanisms reveals a complex network involving STAT3, NF-κB, Hippo, and Wnt/β-catenin pathways, which are dysregulated in gastric cancer caused by H. pylori. Furthermore, we highlight the role of H. pylori in inducing oxidative stress, DNA damage, chronic inflammation, and cell apoptosis-key cellular events that pave the way for carcinogenesis. Emerging evidence also suggests the effect of H. pylori on the tumor microenvironment and its possible implications for cancer immunotherapy. This review synthesizes the current knowledge and identifies gaps that warrant further investigation. Despite the progress in our previous knowledge of the development in H. pylori-induced gastric cancer, a comprehensive investigation of H. pylori's role in gastric cancer is crucial for the advancement of prevention and treatment strategies. By elucidating these mechanisms, we aim to provide a more in-depth insights for the study and prevention of H. pylori-related gastric cancer.
27A systematic review and meta-analysis on the relative and attributable risk of infection and cardia and non-cardia gastric cancer.PubMed
Jianhua Gu, Feifan He, Gary M Clifford, et al.
Expert Rev Mol Diagn. 2023 Jul-Dec;23(12):1251-1261. doi: 10.1080/14737159.2023.2277377. Epub 2023 Dec 15.
INTRODUCTION: This study aimed to update the association between Helicobacter pylori (H. pylori) infection and gastric cancer (GC). METHODS: We searched PubMed, Embase, and Cochrane Library from 1990 to December 2021 to identify prospective studies. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were summarized to validate the relationship between H. pylori infection and GC. RESULTS: Including 27 studies, findings indicated a strong link between H. pylori and non-cardia gastric cancer (NCGC) in both Europe/North America (OR=5.37, 95%CI:4.39-6.57) and Asia (OR = 2.50, 95%CI:1.89-3.32), and a positive association with cardia gastric cancer (CGC) in Asia (OR = 1.74, 95%CI:1.38-2.19), but an inverse association in European/American populations (OR = 0.64, 95%CI: 0.51 to 0.79). Furthermore, the strength of association was greater in studies that detected H. pylori by immunoblotting versus ELISA, and also in studies testing for H. pylori detection further back in time prior to cancer diagnosis (Ptrend<0.05). Approximately 79% of NCGC in Asia and 87% in Europe/North America, along with 62% of CGC in Asia, could be attributable to H. pylori infection. CONCLUSIONS: The meta-analysis supports the significant attributable risk of H. pylori infection for GC and underscores the potential impact of targeting H. pylori in GC prevention programs. PROSPERO REGISTRATION: CRD42021274120.
28Cardia and non-cardia gastric cancer risk associated with Helicobacter pylori in East Asia and the West: A systematic review, meta-analysis, and estimation of population attributable fraction.PubMed
Zhongxue Han, Jing Liu, Wenlin Zhang, et al.
Helicobacter. 2023 Apr;28(2):e12950. doi: 10.1111/hel.12950. Epub 2023 Jan 16.
OBJECTIVES: To assess the region-specific relative risk of cardia/non-cardia gastric cancer (CGC/NCGC) associated with Helicobacter pylori (H. pylori) and quantify its contribution to gastric cancer burden using population attributable fraction (PAF). METHODS: PubMed, EMBASE, Web of Science, and Cochrane Central databases were searched by two reviewers until April 20, 2022. The association between H. pylori infection and NCGC/CGC was assessed using pooled odds ratios (ORs) with 95% confidence intervals (CIs). PAF was calculated using the formula of H. pylori prevalence and the pooled OR. RESULTS: One hundred and eight studies were included. A significant association was observed between H. pylori infection and NCGC in East Asia (OR, 4.36; 95% CI: 3.54-5.37) and the West (OR, 4.03; 95% CI: 2.59-6.27). Regarding CGC, a significant association was found only in East Asia (OR, 2.86; 95% CI: 2.26-3.63), not in the West (OR, 0.80; 95% CI: 0.61-1.05). For studies with a follow-up time of ≥10 years, pooled ORs for NCGC and CGC in East Asia were 5.58 (95% CI: 4.08-7.64) and 3.86 (95% CI: 2.69-5.55), respectively. Pooled OR for NCGC was 6.80 (95% CI: 3.78-12.25) in the West. PAFs showed that H. pylori infection accounted for 71.2% of NCGC, 60.7% of CGC in East Asia, and 73.2% of NCGC in the West. CONCLUSIONS: Gastric cancer burden associated with H. pylori infection exhibits important geographical differences. Prolonged follow-up period could overcome the underestimation of the magnitude of the association between H. pylori infection and CGC/NCGC. Customized strategies for H. pylori screening and eradication should be implemented to prevent gastric cancer.
29Nationwide gastric cancer prevention in China, 2021-2035: a decision analysis on effect, affordability and cost-effectiveness optimisation.PubMed
Zixing Wang, Wei Han, Fang Xue, et al.
Gut. 2022 Dec;71(12):2391-2400. doi: 10.1136/gutjnl-2021-325948. Epub 2022 Jul 28.
OBJECTIVE: To project future trajectories of the gastric cancer (GC) burden in China under different scenarios of GC prevention and identify strategies to improve affordability and cost-effectiveness. DESIGN: Using a cohort of Chinese men and women born during 1951-1980, we assumed that different prevention strategies were conducted, including eradication of (Hp) and endoscopy screening (one-time, annual, biennial, triennial or stratified according to personal risk). We performed a literature search to identify up-to-date data and populate a Markov model to project the number of new GC cases and deaths during 2021-2035, as well as resource requirements and quality-adjusted life-years (QALYs). We examined the impacts of general (among the whole population) and targeted (high-risk population) prevention. RESULTS: During 2021-2035, 10.0 million new GC cases and 5.6 million GC deaths would occur, with 7.6%-35.5% and 6.9%-44.5%, respectively, being avoidable through various prevention strategies. Relative to the status quo, Hp eradication was a cost-saving strategy. General annual screening dominated other screening strategies, but cost more than CNY 70 000 per QALY gained (willingness-to-pay) compared with Hp eradication. Among endoscopy strategies, targeted screening resulted in 44%-49% lower cost per QALY gained over the status quo than general screening. Among high-risk population, tailoring the screening frequency according to personal risk could reduce endoscopy-related resources by 22% compared with biennial screening and by 55% compared with annual screening, CONCLUSION: Our findings provide important input for future decision-making and investment, highlighting the need and feasibility for China to include GC prevention in its national health plans.
30Association Between Helicobacter pylori Eradication and Gastric Cancer Incidence: A Systematic Review and Meta-analysis.PubMed
Yi-Chia Lee, Tsung-Hsien Chiang, Chu-Kuang Chou, et al.
Gastroenterology. 2016 May;150(5):1113-1124.e5. doi: 10.1053/j.gastro.2016.01.028. Epub 2016 Feb 2.
BACKGROUND & AIMS: Eradication of Helicobacter pylori infection has been reported to reduce the risk of gastric cancer among asymptomatic individuals in high-risk areas. The magnitude of benefit of H pylori eradication in populations with different levels of gastric cancer risk and in different clinical scenarios is unclear. We performed a systematic review and meta-analysis of randomized controlled trials and observational studies to investigate the effects of H pylori eradication on the incidence of gastric cancer. METHODS: We searched PubMed, Cochrane Library, and ClinicalTrials.gov, reviewing titles and abstracts of studies of the effects of eradication of H pylori infection on risk of gastric cancer, through May 2015. We also searched bibliographies of included studies, related reviews, and abstracts presented at Digestive Disease Week. Twenty-four eligible studies (22 research manuscripts and 2 abstracts) were included in our meta-analysis (715 incident gastric cancers among a total of 48,064 individuals/340,255 person-years). We assessed the effects, as well as their modification by baseline gastric cancer incidence, study design (randomized trial vs observational study), clinical scenario (asymptomatic infected individuals vs individuals after endoscopic resection of early gastric cancer), demographic characteristics of patients (age and sex), and duration of follow-up. RESULTS: After adjustment for baseline gastric cancer incidence, individuals with eradication of H pylori infection had a lower incidence of gastric cancer than those who did not receive eradication therapy (pooled incidence rate ratio = 0.53; 95% confidence interval: 0.44-0.64). There was little heterogeneity among studies. Baseline gastric cancer incidence modified the benefit of H pylori eradication (P = .037 for interaction); the incidence rate ratio of gastric cancer decreased in a nonlinear fashion with increasing baseline incidence of gastric cancer (P = .018, in comparison with the linear model). The benefit also modestly increased with age (P = .023 for interaction), but this might be due to correlation between age and baseline gastric cancer incidence. Eradication provided significant benefit for asymptomatic infected individuals (pooled incidence rate ratio, 0.62; 95% CI: 0.49-0.79) and individuals after endoscopic resection of gastric cancers (pooled incidence rate ratio, 0.46; 95% CI: 0.35-0.60). The benefits of H pylori eradication did not differ with study design, sex, or follow-up period. CONCLUSIONS: In a systematic review and meta-analysis, we associated eradication of H pylori infection with a reduced incidence of gastric cancer. The benefits of eradication vary with baseline gastric cancer incidence, but apply to all levels of baseline risk.
31Pathobiology of Helicobacter pylori-Induced Gastric Cancer.PubMed
Manuel Amieva, Richard M Peek
Gastroenterology. 2016 Jan;150(1):64-78. doi: 10.1053/j.gastro.2015.09.004. Epub 2015 Sep 16.
Colonization of the human stomach by Helicobacter pylori and its role in causing gastric cancer is one of the richest examples of a complex relationship among human cells, microbes, and their environment. It is also a puzzle of enormous medical importance given the incidence and lethality of gastric cancer worldwide. We review recent findings that have changed how we view these relationships and affected the direction of gastric cancer research. For example, recent data have indicated that subtle mismatches between host and microbe genetic traits greatly affect the risk of gastric cancer. The ability of H pylori and its oncoprotein CagA to reprogram epithelial cells and activate properties of stemness show the sophisticated relationship between H pylori and progenitor cells in the gastric mucosa. The observation that cell-associated H pylori can colonize the gastric glands and directly affect precursor and stem cells supports these observations. The ability to mimic these interactions in human gastric organoid cultures as well as animal models will allow investigators to more fully unravel the extent of H pylori control on the renewing gastric epithelium. Finally, our realization that external environmental factors, such as dietary components and essential micronutrients, as well as the gastrointestinal microbiota, can change the balance between H pylori's activity as a commensal or a pathogen has provided direction to studies aimed at defining the full carcinogenic potential of this organism.
32Single-cell transcriptomic profiling uncovers cellular complexity and microenvironment in gastric tumorigenesis associated with Helicobacter pylori.PubMed
Nianshuang Li, Sihai Chen, Xinbo Xu, et al.
J Adv Res. 2025 Aug;74:471-491. doi: 10.1016/j.jare.2024.10.012. Epub 2024 Oct 15.
INTRODUCTION: Helicobacter pylori (H. pylori) infection is the main risk for gastric cancer (GC). However, the cellular heterogeneity and underlying molecular mechanisms in H. pylori-driven gastric tumorigenesis are poorly understood. OBJECTIVE: Here, we generated a single-cell atlas of gastric tumorigenesis comprising 18 specimens of gastritis, gastric intestinal metaplasia (IM) and GC with or without H. pylori infection. METHODS: Single-cell RNA sequencing (scRNA-seq) was performed. Immunofluorescence, immunohistochemistry and qRT-PCR analysis were applied in a second human gastric tissues cohort for validation. Bioinformatics analyses of public TCGA and GEO datasets were applied. RESULTS: Single-cell RNA profile highlights cellular heterogeneity and alterations in tissue ecology throughout the progression of gastric carcinoma. Various cell lineages exhibited unique cancer-associated expression profiles, such as tumor-like epithelial cell subset (EPC), inflammatory cancer-associated fibroblasts (iCAFs) and Tumor-associated macrophage (TAM). Notably, we revealed that the specific epithelial subset enterocytes from the precancerous lesion GIM, exhibited elevated expression of genes related to lipid metabolism, and HNF4G was predicted as its specific transcription factor. Furthermore, we identified differentially expressed genes in H. pylori-positive and negative epithelial cells, fibroblasts and myeloid cells were identified. Futhermore, H. pylori-positive specimens exhibited enriched cell-cell communication, characterized by significantly active TNF, SPP1, and THY1 signaling networks. CONCLUSIONS: Our study provides a comprehensive landscape of the gastric carcinogenesis ecosystem and novel insights into the molecular mechanisms of different cell types in H. pylori-induced GC.
33Prevalence of chronic atrophic gastritis worldwide from 2010 to 2020: an updated systematic review and meta-analysis.PubMed
Yuan Yin, Hongliang Liang, Na Wei, et al.
Ann Palliat Med. 2022 Dec;11(12):3697-3703. doi: 10.21037/apm-21-1464.
BACKGROUND: Gastric cancer ranks 4th in cancer incidence and ranks 2nd in leading to cancer-related deaths worldwide. The present study aimed to provide an updated overview of the prevalence of chronic atrophic gastritis (CAG), one of the precancerous lesions of gastric cancer, in the recent 10 years and its association with Helicobacter pylori (HP) infection. METHODS: A meta-analysis of follow-up studies worldwide in the recent 10 years was performed by systematically searching in Web of Science, PubMed, Cochrane, and Embase. RESULTS: A total of 14 studies were finally enrolled in the present meta-analysis. The pooled results showed that the prevalence of CAG was about 25% in the study population, and the risk of CAG was about 2.4-fold higher in HP-positive patients than in those who were HP negative. Subgroup analyses showed that both the prevalence of CAG and the risk of CAG in HP-positive patients were higher when infection was diagnosed by histology than by serology. CONCLUSIONS: The worldwide prevalence of CAG is still high, and HP infection remains an important risk factor for CAG. Future studies of large-scale are still in urgent need to further control the prevalence of CAG, so as to reduce the burden of gastric cancer.
34Characteristics and Early Diagnosis of Gastric Cancer Discovered after Eradication.PubMed
Masanori Ito, Shinji Tanaka, Kazuaki Chayama
Gut Liver. 2021 May 15;15(3):338-345. doi: 10.5009/gnl19418.
The prevalence of gastric cancer after eradication (GCAE) is increasing dramatically in Japan. GCAE has characteristic features, and we must understand these features in endoscopic examinations. Differentiated cancer types were frequently found after eradication and included characteristic endoscopic features such as reddish depression (RD). However, benign RD can be difficult to distinguish from gastric cancer because of histological alterations in the surface structures (nonneoplastic epithelium or epithelium with low-grade atypia [ELA]) as well as multiple appearances of RD. Recently, we clarified similar alterations in genetic mutations between ELA and gastric cancer, suggesting that ELA is derived from gastric cancer. Clinically, submucosal invasive cancer was frequently found in patients after eradication therapy even if they received annual endoscopic surveillance. We can improve the diagnostic ability using image-enhanced endoscopy with magnified observation.
35Gastric cancer prevention by community eradication of Helicobacter pylori: a cluster-randomized controlled trial.PubMed
Kai-Feng Pan, Wen-Qing Li, Lian Zhang, et al.
Nat Med. 2024 Nov;30(11):3250-3260. doi: 10.1038/s41591-024-03153-w. Epub 2024 Jul 30.
Gastric cancer is a leading cause of cancer-related deaths in China. Affecting more than 40% of the world's population, Helicobacter pylori is a major risk factor for gastric cancer. While previous clinical trials indicated that eradication of H. pylori could reduce gastric cancer risk, this remains to be shown using a population-based approach. We conducted a community-based, cluster-randomized, controlled, superiority intervention trial in Linqu County, China, with individuals who tested positive for H. pylori using a C-urea breath test randomly assigned to receiving either (1) a 10-day, quadruple anti-H. pylori treatment (comprising 20 mg of omeprazole, 750 mg of tetracycline, 400 mg of metronidazole and 300 mg of bismuth citrate) or (2) symptom alleviation treatment with a single daily dosage of omeprazole and bismuth citrate. H. pylori-negative individuals did not receive any treatment. We examined the incidence of gastric cancer as the primary outcome. A total of 180,284 eligible participants from 980 villages were enrolled over 11.8 years of follow-up, and a total of 1,035 cases of incident gastric cancer were documented. Individuals receiving anti-H. pylori therapy showed a modest reduction in gastric cancer incidence in intention-to-treat analyses (hazard ratio 0.86, 95% confidence interval 0.74-0.99), with a stronger effect observed for those having successful H. pylori eradication (hazard ratio 0.81, 95% confidence interval 0.69-0.96) than for those who failed treatment. Moderate adverse effects were reported in 1,345 participants during the 10-day treatment. We observed no severe intolerable adverse events during either treatment or follow-up. The findings suggest the potential for H. pylori mass screening and eradication as a public health policy for gastric cancer prevention. Chinese Clinical Trial Registry identifier: ChiCTR-TRC-10000979 .
36Helicobacter pylori Treatment and Gastric Cancer Risk Among Individuals With High Genetic Risk for Gastric Cancer.PubMed
Heng-Min Xu, Yuting Han, Zong-Chao Liu, et al.
JAMA Netw Open. 2024 May 1;7(5):e2413708. doi: 10.1001/jamanetworkopen.2024.13708.
IMPORTANCE: Helicobacter pylori treatment and nutrition supplementation may protect against gastric cancer (GC), but whether the beneficial effects only apply to potential genetic subgroups and whether high genetic risk may be counteracted by these chemoprevention strategies remains unknown. OBJECTIVE: To examine genetic variants associated with the progression of gastric lesions and GC risk and to assess the benefits of H pylori treatment and nutrition supplementation by levels of genetic risk. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used follow-up data of the Shandong Intervention Trial (SIT, 1989-2022) and China Kadoorie Biobank (CKB, 2004-2018) in China. Based on the SIT, a longitudinal genome-wide association study was conducted to identify genetic variants for gastric lesion progression. Significant variants were examined for incident GC in a randomly sampled set of CKB participants (set 1). Polygenic risk scores (PRSs) combining independent variants were assessed for GC risk in the remaining CKB participants (set 2) and in an independent case-control study in Linqu. EXPOSURES: H pylori treatment and nutrition supplementation. MAIN OUTCOMES AND MEASURES: Primary outcomes were the progression of gastric lesions (in SIT only) and the risk of GC. The associations of H pylori treatment and nutrition supplementation with GC were evaluated among SIT participants with different levels of genetic risk. RESULTS: Our analyses included 2816 participants (mean [SD] age, 46.95 [9.12] years; 1429 [50.75%] women) in SIT and 100 228 participants (mean [SD] age, 53.69 [11.00] years; 57 357 [57.23%] women) in CKB, with 147 GC cases in SIT and 825 GC cases in CKB identified during follow-up. A PRS integrating 12 genomic loci associated with gastric lesion progression and incident GC risk was derived, which was associated with GC risk in CKB (highest vs lowest decile of PRS: hazard ratio [HR], 2.54; 95% CI, 1.80-3.57) and further validated in the analysis of 702 case participants and 692 control participants (mean [SD] age, 54.54 [7.66] years; 527 [37.80%] women; odds ratio, 1.83; 95% CI, 1.11-3.05). H pylori treatment was associated with reduced GC risk only for individuals with high genetic risk (top 25% of PRS: HR, 0.45; 95% CI, 0.25-0.82) but not for those with low genetic risk (HR, 0.81; 95% CI, 0.50-1.34; P for interaction = .03). Such effect modification was not found for vitamin (P for interaction = .93) or garlic (P for interaction = .41) supplementation. CONCLUSIONS AND RELEVANCE: The findings of this cohort study indicate that a high genetic risk of GC may be counteracted by H pylori treatment, suggesting primary prevention could be tailored to genetic risk for more effective prevention.
37Pathogenesis of Helicobacter pylori infection.PubMed
Johannes G Kusters, Arnoud H M van Vliet, Ernst J Kuipers
Clin Microbiol Rev. 2006 Jul;19(3):449-90. doi: 10.1128/CMR.00054-05.
Helicobacter pylori is the first formally recognized bacterial carcinogen and is one of the most successful human pathogens, as over half of the world's population is colonized with this gram-negative bacterium. Unless treated, colonization usually persists lifelong. H. pylori infection represents a key factor in the etiology of various gastrointestinal diseases, ranging from chronic active gastritis without clinical symptoms to peptic ulceration, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. Disease outcome is the result of the complex interplay between the host and the bacterium. Host immune gene polymorphisms and gastric acid secretion largely determine the bacterium's ability to colonize a specific gastric niche. Bacterial virulence factors such as the cytotoxin-associated gene pathogenicity island-encoded protein CagA and the vacuolating cytotoxin VacA aid in this colonization of the gastric mucosa and subsequently seem to modulate the host's immune system. This review focuses on the microbiological, clinical, immunological, and biochemical aspects of the pathogenesis of H. pylori.
38Peptic ulcer pathophysiology.PubMed
H R Mertz, J H Walsh
Med Clin North Am. 1991 Jul;75(4):799-814. doi: 10.1016/s0025-7125(16)30412-6.
Despite extensive research, the etiology of peptic ulcer disease remains unclear. Given the multiple processes that control acid and pepsin secretion and defense and repair of the gastroduodenal mucosa, it is likely that the cause of ulceration differs between individuals. Acid and pepsin appear to be necessary but not sufficient ingredients in the ulcerative process. It is clear that the majority of gastric ulcers and a substantial number of duodenal ulcers do not have increased gastric acid secretion. Recent research has focused more on protection and repair of the stomach and duodenum. NSAIDs cause a significant number of gastric and duodenal ulcers; this is probably due to inhibition of prostaglandin production with loss of its protective effects. In the absence of NSAIDs and gastrinoma, it appears that most gastric ulcers and all duodenal ulcers occur in the setting of H. pylori infection. Evidence is mounting in support of H. pylori as a necessary ingredient in the ulcerative process, similar to acid and pepsin. It is not known whether the bacteria or the accompanying inflammation is the more important factor in the pathophysiology. Although the pathophysiology of gastric ulcer and duodenal ulcer is similar, there are clearly differences between the two groups. Duodenal ulcer is typified by H. pylori infection and duodenitis and in many cases impaired duodenal bicarbonate secretion in the face of moderate increases in acid and peptic activity. These facts suggest the following process: increased peptic activity coupled with decreased duodenal buffering capacity may lead to increased mucosal injury and result in gastric metaplasia. In the presence of antral H. pylori, the gastric metaplasia can become colonized and inflamed. The inflammation or the infection itself then disrupts the process of mucosal defense or regeneration resulting in ulceration. A cycle of further injury and increased inflammation with loss of the framework for regeneration may then cause a chronic ulcer. Gastric ulcer often occurs with decreased acid-peptic activity, suggesting that mucosal defensive impairments are more important. The combination of inflammation, protective deficiencies, and moderate amounts of acid and pepsin may be enough to induce ulceration. Many questions remain in understanding the pathophysiology of peptic ulcer disease. The physiology and pathophysiology of mucosal regeneration and the mechanisms by which H. pylori and inflammation disrupt normal gastroduodenal function will be fruitful areas of future investigation.
39Helicobacter pylori infection.PubMed
Peter Malfertheiner, M Constanza Camargo, Emad El-Omar, et al.
Nat Rev Dis Primers. 2023 Apr 20;9(1):19. doi: 10.1038/s41572-023-00431-8.
Helicobacter pylori infection causes chronic gastritis, which can progress to severe gastroduodenal pathologies, including peptic ulcer, gastric cancer and gastric mucosa-associated lymphoid tissue lymphoma. H. pylori is usually transmitted in childhood and persists for life if untreated. The infection affects around half of the population in the world but prevalence varies according to location and sanitation standards. H. pylori has unique properties to colonize gastric epithelium in an acidic environment. The pathophysiology of H. pylori infection is dependent on complex bacterial virulence mechanisms and their interaction with the host immune system and environmental factors, resulting in distinct gastritis phenotypes that determine possible progression to different gastroduodenal pathologies. The causative role of H. pylori infection in gastric cancer development presents the opportunity for preventive screen-and-treat strategies. Invasive, endoscopy-based and non-invasive methods, including breath, stool and serological tests, are used in the diagnosis of H. pylori infection. Their use depends on the specific individual patient history and local availability. H. pylori treatment consists of a strong acid suppressant in various combinations with antibiotics and/or bismuth. The dramatic increase in resistance to key antibiotics used in H. pylori eradication demands antibiotic susceptibility testing, surveillance of resistance and antibiotic stewardship.
40Helicobacter pylori and benign upper digestive disease.PubMed
Larry H Lai, Joseph J Y Sung
Best Pract Res Clin Gastroenterol. 2007;21(2):261-79. doi: 10.1016/j.bpg.2006.10.002.
Acute infection with Helicobacter pylori causes hypochlorhydria and gastrointestinal upset. As the infection persists, patients develop chronic antral-predominant or pangastritis. Gastric and duodenal ulcers arise from chronic mucosal inflammation and disordered acid secretion in the stomach. With successful eradication of H. pylori, non-NSAID-related gastric and duodenal ulcers heal even without long-term acid suppression. More importantly, peptic ulcers and their complications rarely recur. Clearing H. pylori infection also reduces the risk of mucosal injury in NSAID and aspirin users; the protective effects are more pronounced in NSAID-naïve and aspirin users. H. pylori is unlikely to be the cause of gastro-oesophageal reflux disease. However, a patient's reflux symptoms may be more difficult to control after clearing the infection. Although there is little evidence to support a causal relationship between H. pylori and non-ulcer dyspepsia, treatment of the infection gives a modest improvement of symptoms.
41Helicobacter pylori: an up-to-date overview on the virulence and pathogenesis mechanisms.PubMed
Hyelnaya Cletus Sharndama, Ifeanyi Elibe Mba
Braz J Microbiol. 2022 Mar;53(1):33-50. doi: 10.1007/s42770-021-00675-0. Epub 2022 Jan 6.
Helicobacter pylori is an organism associated with ulcer disease and gastric cancer. The latter is one of the most prevalent malignancies and currently the fourth major cause of cancer-related deaths globally. The pathogen infects about 50% of the world population, and currently, no treatment ensures its total elimination. There has been an increase in our understanding of the pathophysiology and pathogenesis mechanisms of H. pylori over the years. H. pylori can induce several genetic alterations, express numerous virulence factors, and trigger diverse adaptive mechanisms during its adherence and colonization. For successful colonization and infection establishment, several effector proteins/toxins are released by the organism. Evidence is also available reporting spiral to coccoid transition as a unique tactic H. pylori uses to survive in the host's gastrointestinal tract (GIT). Thus, the virulence and pathogenicity of H. pylori are under the control of complex interplay between the virulence factors, host, and environmental factors. Expounding the role of the various virulence factors in H. pylori pathogenesis and clinical outcomes is crucial for vaccine development and in providing and developing a more effective therapeutic intervention. Here we critically reflect on H. pylori infection and delineate what is currently known about the virulence and pathogenesis mechanisms of H. pylori.
42Chronic Atrophic Gastritis: A Review.PubMed
Yifei Li, Ran Xia, Bo Zhang, et al.
J Environ Pathol Toxicol Oncol. 2018;37(3):241-259. doi: 10.1615/JEnvironPatholToxicolOncol.2018026839.
Chronic atrophic gastritis is a generally asymptomatic condition of great importance because it develops into gastric cancer in a number of patients. It is described as an atrophy of the gastric mucosa. There are two types of atrophic gastritis: a gastric body predominant type in patients with infection of Helicobacter pylori, and an autoimmune type, limited to the gastric body and fundus. The autoimmune type is quite rare and affects people of all ethnicities. Globally, H. pylori infection is very common and is considered a class I carcinogen due to the large number of patients who subsequently develop gastric cancer. The pathogenesis of the autoimmune type involves an antibody-mediated loss of parietal cells resulting in achlorhydria and an antibody-mediated loss of intrinsic factor that causes pernicious anemia. The diagnosis of H. pylori infection is based on endoscopy and culture of the organisms. Patients with atrophic gastritis as well as H. pylori infection should be treated with antibiotics to eradicate the organism. Patients with the autoimmune type need to be evaluated for anemia, and if present, treated with vitamin B12.
43Research on drug treatment and the novel signaling pathway of chronic atrophic gastritis.PubMed
Jinhao Jia, Huijie Zhao, Fangfei Li, et al.
Biomed Pharmacother. 2024 Jul;176:116912. doi: 10.1016/j.biopha.2024.116912. Epub 2024 Jun 7.
BACKGROUND: Chronic atrophic gastritis (CAG) is a global digestive system disease and one of the important causes of gastric cancer. The incidence of CAG has been increasing yearly worldwide. PURPOSE: This article reviews the latest research on the common causes and future therapeutic targets of CAG as well as the pharmacological effects of corresponding clinical drugs. We provide a detailed theoretical basis for further research on possible methods for the treatment of CAG and reversal of the CAG process. RESULTS: CAG often develops from chronic gastritis, and its main pathological manifestation is atrophy of the gastric mucosa, which can develop into gastric cancer. The drug treatment of CAG can be divided into agents that regulate gastric acid secretion, eradicate Helicobacter. pylori (H. pylori), protect gastric mucous membrane, or inhibit inflammatory factors according to their mechanism of action. Although there are limited specific drugs for the treatment of CAG, progress is being made in defining the pathogenesis and therapeutic targets of the disease. Growing evidence shows that NF-κB, PI3K/AKT, Wnt/ β-catenin, MAPK, Toll-like receptors (TLRs), Hedgehog, and VEGF signaling pathways play an important role in the development of CAG.
44Pathogenesis and potential reversibility of intestinal metaplasia - a milestone in gastric carcinogenesis.PubMed
Jan Drnovsek, Matjaz Homan, Nina Zidar, et al.
Radiol Oncol. 2024 Apr 21;58(2):186-195. doi: 10.2478/raon-2024-0028. eCollection 2024 Jun 1.
BACKGROUND: Non-cardia gastric cancer remains a major cause of cancer-related mortality worldwide, despite declining incidence rates in many industrialized countries. The development of intestinal-type gastric cancer occurs through a multistep process in which normal mucosa is sequentially transformed into hyperproliferative epithelium, followed by metaplastic processes leading to carcinogenesis. Chronic infection with is the primary etiological agent that causes chronic inflammation of the gastric mucosa, induces atrophic gastritis, and can lead to intestinal metaplasia and dysplasia. Both intestinal metaplasia and dysplasia are precancerous lesions, in which gastric cancer is more likely to occur. Atrophic gastritis often improves after eradication of ; however, the occurrence of intestinal metaplasia has been traditionally regarded as "the point of no return" in the carcinogenesis sequence. eradication heals non-atrophic chronic gastritis, may lead to regression of atrophic gastritis, and reduces the risk of gastric cancer in patients with these conditions. In this article, we discuss the pathogenesis, epigenomics, and reversibility of intestinal metaplasia and briefly touch upon potential treatment strategy. CONCLUSIONS: Gastric intestinal metaplasia no longer appears to be an irreversible precancerous lesion. However, there are still many controversies regarding the improvement of intestinal metaplasia after eradication.
45ACG and CAG Clinical Guideline: Management of Dyspepsia.PubMed
Paul Moayyedi, Brian E Lacy, Christopher N Andrews, et al.
Am J Gastroenterol. 2017 Jul;112(7):988-1013. doi: 10.1038/ajg.2017.154. Epub 2017 Jun 20.
We have updated both the American College of Gastroenterology (ACG) and the Canadian Association of Gastroenterology (CAG) guidelines on dyspepsia in a joint ACG/CAG dyspepsia guideline. We suggest that patients ≥60 years of age presenting with dyspepsia are investigated with upper gastrointestinal endoscopy to exclude organic pathology. This is a conditional recommendation and patients at higher risk of malignancy (such as spending their childhood in a high risk gastric cancer country or having a positive family history) could be offered an endoscopy at a younger age. Alarm features should not automatically precipitate endoscopy in younger patients but this should be considered on a case-by-case basis. We recommend patients <60 years of age have a non-invasive test Helicobacter pylori and treatment if positive. Those that are negative or do not respond to this approach should be given a trial of proton pump inhibitor (PPI) therapy. If these are ineffective tricyclic antidepressants (TCA) or prokinetic therapies can be tried. Patients that have an endoscopy where no pathology is found are defined as having functional dyspepsia (FD). H. pylori eradication should be offered in these patients if they are infected. We recommend PPI, TCA and prokinetic therapy (in that order) in those that fail therapy or are H. pylori negative. We do not recommend routine upper gastrointestinal (GI) motility testing but it may be useful in selected patients.
46Helicobacter pylori: friend or foe?PubMed
Stephen David Howard Malnick, Ehud Melzer, Malka Attali, et al.
World J Gastroenterol. 2014 Jul 21;20(27):8979-85. doi: 10.3748/wjg.v20.i27.8979.
Helicobacter pylori (H. pylori) is a Gram-negative spiral bacterium that is present in nearly half the world's population. It is the major cause of peptic ulcer disease and a recognized cause of gastric carcinoma. In addition, it is linked to non-ulcer dyspepsia, vitamin B12 deficiency, iron-deficient anemia and immune thrombocytopenic purpura. These conditions are indications for testing and treatment according to current guidelines. An additional indication according to the guidelines is "anyone with a fear of gastric cancer" which results in nearly every infected person being eligible for eradication treatment. There may be beneficial effects of H. pylori in humans, including protection from gastroesophageal reflux disease and esophageal adenocarcinoma. In addition, universal treatment will be extremely expensive (more than $32 billion in the United States), may expose the patients to adverse effects such as anaphylaxis and Clostridium difficile infection, as well as contributing to antibiotic resistance. There may also be an as yet uncertain effect on the fecal microbiome. There is a need for robust clinical data to assist in decision-making regarding treatment of H. pylori infection.
47Microbiota in the stomach and application of probiotics to gastroduodenal diseases.PubMed
Yasuhiro Koga
World J Gastroenterol. 2022 Dec 21;28(47):6702-6715. doi: 10.3748/wjg.v28.i47.6702.
The stomach is a hostile environment for most microbes because strong gastric acid kills indigenous microorganisms. Thus, the mass of indigenous microbes detected by traditional culturing method in a highly acidic stomach is reported to be very small. However, in a stomach with less acidity due to atrophic changes of the gastric mucosa, the number of live gastric microbiota dramatically increases and their composition changes. A probiotic is defined as a live microorganism that, when administered in adequate amounts, confers a health benefit on the host. The administration of probiotics to the stomach has thus far been considered impractical, mainly due to the strong acidity in the stomach. The identification of candidate probiotic strains with sufficient resistance to acidity and the ability to achieve close proximity to the gastric mucosa could enable the application of probiotics to the stomach. The utilization of probiotics alone for () infection significantly improves gastric mucosal inflammation and decreases the density of on the mucosa, although complete eradication of has not yet been demonstrated. The use of probiotics in combination with antimicrobial agents significantly increases the eradication rate, especially when the strains are resistant to antimicrobial agents. While has been considered the most important pathogenic bacterium for the development of gastric cancer, bacteria other than are also suggested to be causative pathogens that promote the development of gastric cancer, even after the eradication of . Increased non- Gram-negative bacteria in the stomach with weak acidity accompanying atrophic gastritis may perpetuate gastric mucosal inflammation and accelerate carcinogenic progression, even after eradication. Probiotics restore the acidity in this stomach environment and may therefore prevent the development of gastric cancer by termination of Gram-negative bacteria-induced inflammation. Functional dyspepsia (FD) is defined as the presence of symptoms that are thought to originate in the gastroduodenal region in the absence of any organic, systematic or metabolic diseases. Accumulating evidence has pointed out the duodenum as a target region underlying the pathophysiology of FD. A randomized placebo-controlled clinical trial using a probiotic strain (LG21) demonstrated a significant improving effect on major FD symptoms. One of the possible mechanisms of this effect is protection of the duodenal mucosa from injurious intestinal bacteria through the resolution of small intestinal bacterial over growth.
48Effects of infection on intestinal microbiota, immunity and colorectal cancer risk.PubMed
Veronika Engelsberger, Markus Gerhard, Raquel Mejías-Luque
Front Cell Infect Microbiol. 2024 Jan 26;14:1339750. doi: 10.3389/fcimb.2024.1339750. eCollection 2024.
Infecting about half of the world´s population, is one of the most prevalent bacterial infections worldwide and the strongest known risk factor for gastric cancer. Although colonizes exclusively the gastric epithelium, the infection has also been associated with various extragastric diseases, including colorectal cancer (CRC). Epidemiological studies reported an almost two-fold increased risk for infected individuals to develop CRC, but only recently, direct causal and functional links between the chronic infection and CRC have been revealed. Besides modulating the host intestinal immune response, is thought to increase CRC risk by inducing gut microbiota alterations. It is known that infection not only impacts the gastric microbiota at the site of infection but also leads to changes in bacterial colonization in the distal large intestine. Considering that the gut microbiome plays a driving role in CRC, infection emerges as a key factor responsible for promoting changes in microbiome signatures that could contribute to tumor development. Within this review, we want to focus on the interplay between infection, changes in the intestinal microbiota, and intestinal immunity. In addition, the effects of antibiotic eradication therapy will be discussed.
49infection: Beyond gastric manifestations.PubMed
Maria Luísa Cordeiro Santos, Breno Bittencourt de Brito, Filipe Antônio França da Silva, et al.
World J Gastroenterol. 2020 Jul 28;26(28):4076-4093. doi: 10.3748/wjg.v26.i28.4076.
() is a bacterium that infects more than a half of world's population. Although it is mainly related to the development of gastroduodenal diseases, several studies have shown that such infection may also influence the development and severity of various extragastric diseases. According to the current evidence, whereas this bacterium is a risk factor for some of these manifestations, it might play a protective role in other pathological conditions. In that context, when considered the gastrointestinal tract, positivity have been related to Inflammatory Bowel Disease, Gastroesophageal Reflux Disease, Non-Alcoholic Fatty Liver Disease, Hepatic Carcinoma, Cholelithiasis, and Cholecystitis. Moreover, lower serum levels of iron and vitamin B12 have been found in patients with infection, leading to the emergence of anemias in a portion of them. With regards to neurological manifestations, a growing number of studies have associated that bacterium with multiple sclerosis, Alzheimer's disease, Parkinson's disease, and Guillain-Barré syndrome. Interestingly, the risk of developing cardiovascular disorders, such as atherosclerosis, is also influenced by the infection. Besides that, the -associated inflammation may also lead to increased insulin resistance, leading to a higher risk of diabetes mellitus among infected individuals. Finally, the occurrence of dermatological and ophthalmic disorders have also been related to that microorganism. In this sense, this minireview aims to gather the main studies associating infection with extragastric conditions, and also to explore the main mechanisms that may explain the role of in those diseases.
50[Research Progress of -Associated Extragastric Diseases].PubMed
Jin-Yang Liu, Zheng-Hong Chen, Mu-Xi Ma, et al.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2024 Jun;46(3):414-424. doi: 10.3881/j.issn.1000-503X.15698.
(Hp) is a common Gram-negative bacillus causing gastrointestinal infections.It mainly exists on the surface of gastric epithelial cells and in mucus and is associated with gastric ulcers,gastric cancer,and gastric mucosa-associated lymphomas.Studies have shown that Hp can induce or exacerbate certain extragastric diseases and is associated with the occurrence of coronavirus disease 2019.It is hypothesized that Hp may be indirectly or directly involved in the occurrence and development of diseases by stimulating the production of inflammatory cytokines or inducing cross-immune reactions.In addition,Hp can enter to release toxins continuously and play a role in escaping the recognition of the host immune system and the bactericidal effect of drugs.This article reviews the research progress in Hp-associated extragastric diseases in recent years,aiming to draw the attention of clinical workers to Hp-associated extragastric diseases and enrich the knowledge about Hp infection for formulating countermeasures to avoid the aggravation or triggering of other diseases by Hp.
51Helicobacter pylori and Extragastric Diseases.PubMed
Andreas Kyburz, Anne Müller
Curr Top Microbiol Immunol. 2017;400:325-347. doi: 10.1007/978-3-319-50520-6_14.
The Gram-negative bacterium Helicobacter pylori is predominantly known for its tight association with peptic ulcer disease and gastric cancer development. However, recent epidemiological and experimental evidence suggests that chronic infection with H. pylori may at the same time be beneficial to the host by conferring protection against gastroesophageal diseases, asthma, other allergic disease manifestations and inflammatory bowel diseases (IBD). In this chapter, we summarize the epidemiological data that are available to date to support or refute a possible inverse correlation of H. pylori infection with various extragastric diseases. We further examine and discuss the experimental evidence, generated mostly in mouse models of allergic diseases and IBD, showing that these disorders fail to develop in the presence of H. pylori. The proposed mechanisms of the protective effects of H. pylori, which appear to involve the induction of regulatory T-cells (Tregs) with highly suppressive activity, are presented and explained.
52Helicobacter pylori infection in skin diseases: a critical appraisal.PubMed
Bettina Wedi, Alexander Kapp
Am J Clin Dermatol. 2002;3(4):273-82. doi: 10.2165/00128071-200203040-00005.
More than 50% of the human population have long-term Helicobacter pylori infection, causing, in some cases, severe diseases such as peptic ulcers and stomach cancer. In the last few years several extra-gastrointestinal disorders have been associated with H. pylori infection. This review summarized the current medical literature, identified through hand searching and MEDLINE research, including our own studies, with regard to H. pylori and skin diseases. From the literature it can be seen that the role of H. pylori in skin diseases is still a controversial subject. Randomized controlled trials with adequate masking and sample sizes are still lacking. The best evidence comes from studies investigating chronic urticaria in which chronic urticaria disappeared in many patients with H. pylori infection after careful eradication of the H. pylori. Moreover, there are promising recent reports of beneficial H. pylori eradication in Behçet's disease, pruritus cutaneus, prurigo chronica, prurigo nodularis and in some patients with lichen planus, but not in rosacea or psoriasis. Before any conclusions with respect to other skin diseases such as atopic dermatitis, Schoenlein-Henoch Purpura, Sweet's syndrome, Sjögren syndrome or systemic sclerosis may be drawn, additional randomized, double-blinded and placebo-controlled studies including adequate diagnostic schedules, sufficient eradication treatment protocols, confirmation of eradication and adequate control groups are needed. The cutaneous pathology of H. pylori is far from being clear, but it is speculated that the systemic effects may involve increased mucosal permeability to alimentary antigens, immunomodulation, an autoimmune mechanism or the impairment of vascular integrity.
53[Infections and chronic spontaneous urticaria. A review].PubMed
B Wedi, U Raap, D Wieczorek, et al.
Hautarzt. 2010 Sep;61(9):758-64. doi: 10.1007/s00105-010-1930-y.
Urticaria represents a common skin reaction pattern that can be induced by different factors. Triggering by infections has been discussed for many years but the exact role and mechanism of mast cell activation by infectious processes is unclear. In acute spontaneous urticaria, there is no doubt about a causal relationship to infections and all chronic urticaria must start as acute. Remission of annoying spontaneous chronic urticaria has been reported after successful treatment of persistent infections. Summarizing available studies evaluating the course after proven Helicobacter eradication demonstrates a statistically significant benefit compared to not-eradicated or Helicobacter-negative patients. The licensed treatment with a standard dose of H1-antihistamines is not effective in a significant number of patients and infections can be easily treated. Therefore, appropriate diagnostic procedures should be included in the routine work-up, especially the search for Helicobacter pylori.
54Potential contribution of Helicobacter pylori proteins in the pathogenesis of type 1 gastric neuroendocrine tumor and urticaria. In silico approach.PubMed
Andrés Sánchez Caraballo, Yenny Guzmán, Jorge Sánchez, et al.
PLoS One. 2023 Apr 25;18(4):e0281485. doi: 10.1371/journal.pone.0281485. eCollection 2023.
BACKGROUND: Helicobacter pylori has been linked to several diseases such as chronic urticaria, gastritis, and type 1 gastric neuroendocrine tumors (type 1 gNET). Although these diseases seem to have different mechanisms, their relationship with H. pylori suggests a common inflammatory pathway. OBJECTIVE: To identify potential cross-reactive antigens between H. pylori and humans involved in chronic urticaria and type 1 gNET. METHODS: Alignment was carried out among human proteins associated with urticaria (9 proteins), type 1 gNET (32 proteins), and H. pylori proteome. We performed pairwise alignment among the human and H. pylori antigens with PSI-BLAST. Modeling based on homology was done with the Swiss model server and epitope prediction with the Ellipro server. Epitopes were located on a 3D model using PYMOL software. RESULTS: The highest conserved sequence was found between the human HSP 60 antigen and the H. pylori chaperonin GroEL with an identity of 54% and a cover of 92%, followed by the alpha and gamma enolases and two H. pylori phosphopyruvate hydratase, both with an identity and cover of 48% and 96%, respectively. The H/K ATPase (Chain A) showed high identity with two H. pylori proteins (35.21% with both P-type ATPase), but with low cover (only 6%). We observed eight linear and three discontinuous epitopes for human HSP 60 and three lineal and one discontinuous epitope for both alpha-enolase and gamma enolase, high conserved with H. pylori sequences. CONCLUSION: Some type 1 gNET antigens shared potential cross-reactive epitopes with H. pylori proteins, suggesting that molecular mimicry could be a mechanism that explains the relationship between the infection and this disease. Studies evaluating the functional impact of this relationship are needed.
55Microorganisms associated to thyroid autoimmunity.PubMed
Yunam Cuan-Baltazar, Elena Soto-Vega
Autoimmun Rev. 2020 Sep;19(9):102614. doi: 10.1016/j.autrev.2020.102614. Epub 2020 Jul 11.
Autoimmune thyroid diseases are a group of diseases characterized by a dysfunction of the immune system concerning the thyroid gland, associated with hypothyroidism or hyperthyroidism. The thyroid gland autoimmunity has been recognized as multifactorial. It has been reported that microorganisms may play a role on the pathogenesis of Hashimoto's thyroiditis and Graves´ disease. These could explain the high incidence of the autoimmune thyroid diseases. Helicobacter Pylori (H. pylori) and Hepatitis C virus (HCV) are the microorganisms in which the association with autoimmune thyroid diseases is clearer. The pathophysiologic mechanisms are still not well defined. For H. pylori, molecular mimicry has been the most accepted mechanism. It has been proposed Hepatitis C virus as the trigger of the thyroid autoimmunity by exacerbating the production of thyroid auto-antibodies, while some mention that the real factor that triggers the thyroid autoimmunity is the treatment with Interferon alpha (IFN-alpha) by upregulating MHC class I and inducing ligation of CD40+ cells to thyrocytes. Other microorganisms such as Toxoplasma gondii, Human Immunodeficiency virus, Herpes virus and others have reported information about their association with thyroid autoimmune diseases There are no proposals on how these last microorganisms induce thyroid autoimmunity. There is still a lack of evidence on this topic. Further research must be done to determine the interaction of these microorganisms and the best way to manage these patients.
56Helicobacter pylori CagA antibodies and thyroid function in latent autoimmune diabetes in adults.PubMed
A P Delitala, G M Pes, A Errigo, et al.
Eur Rev Med Pharmacol Sci. 2016 Oct;20(19):4041-4047.
OBJECTIVE: H. pylori infection is reportedly associated with autoimmune diseases such as chronic thyroiditis and autoimmune diabetes. The aim of this study is to determine the association between H. pylori infection and its virulent strain CagA with antibodies against thyroperoxidase (TPO Ab) and thyrotropin (TSH) in a cohort of latent autoimmune diabetes in adult (LADA) patients. PATIENTS AND METHODS: We included 234 LADA patients (53.8% women). Antibodies against H. pylori whole antigens and CagA, TPO Ab and TSH were assessed in all patients. RESULTS: Prevalence of IgG against H. pylori and GagA was 52.1% and 20.9% respectively. Antibodies against H. pylori were not associated with TPO Ab and TSH (rho = 0.067, p = 0.620 and rho = 0.156, p = 0.099, respectively). Antibodies against CagA showed a positive association with TSH and TPO Ab (respectively rho = 0.309, p = 0.036 and rho = 0.419, p = 0.037). Subjects with hypothyroidism (TSH ≥ 3.5 μU/ml) had an increased frequency of Ab anti CagA (p = 0.059). CONCLUSIONS: The infection by H. pylori strains expressing CagA is associated with increased TPO Ab and TSH levels in LADA patients, suggesting a possible mechanism involved in thyroid autoimmunity and dysfunction of the gland. Further research is needed to test this hypothesis.
57Lack of humoral response against Helicobacter pylori peptides homologous to human ZnT8 in Hashimoto's thyroiditis patients.PubMed
Speranza Masala, Davide Cossu, Magdalena Niegowska, et al.
J Infect Dev Ctries. 2015 Jul 4;9(6):631-4. doi: 10.3855/jidc.6284.
INTRODUCTION: The Helicobacter pylori (HP) reinfection rate seems to be higher in developing countries than in developed ones. An increased seroprevalence of HP has also been reported in patients with type 1 diabetes (T1D) and Hashimoto's thyroiditis (HT). Mycobacterium avium subsp. paratuberculosis (MAP) has been linked to both T1D and HT. Quite a few lines of evidence indicate that autoantibodies against several epitopes belonging to human zinc transporter 8 (ZnT8) cross-recognize the homologous MAP3865c epitopes in both T1D and HT patients. HP may play a role in HT disease, most likely acting through a molecular mimicry mechanism that targets ZnT8 as reported for MAP and the two autoimmune diseases. METHODOLOGY: An enzyme-linked immunosorbent assay (ELISA) has been developed for the detection of antibodies against several epitopes deriving from HP proteins, which are highly homologous to the immunodominant ZnT8 peptides previously identified: ZnT8178-186 and ZnT8186-194. RESULTS: None of the HP peptides tested were significantly recognized when the humoral responses of 92 HT patients and 91 healthy volunteers were analyzed. CONCLUSIONS: These findings do not support a triggering role for HP (through ZnT8 mimicking) in HT. If a molecular mimicry phenomenon is taking place, it involves a different self-antigen. Moreover, the negative outcome of the experiments performed stresses the fact that sharing stretches of sequence homology is relevant, but not enough to trigger an antibody-mediated cross-recognition.
58Influence of Helicobacter pylori infection on risk of rheumatoid arthritis: a nationwide population-based study.PubMed
Tzu-Hsuan Lee, Meng-Che Wu, Ming-Hung Lee, et al.
Sci Rep. 2023 Sep 13;13(1):15125. doi: 10.1038/s41598-023-42207-w.
The relationship between Helicobacter pylori infection and rheumatoid arthritis has been investigated, but the results remain controversial. This study aims to determine the association between the two diseases via a 17-year retrospective cohort study. Using the National Health Insurance Research Database, a nationwide population based in Taiwan, we identified 97,533 individuals with H. pylori infection and matched controls between 2000 and 2017 using propensity score matching at a 1:1 ratio. The adjusted hazard ratio of rheumatoid arthritis was determined by multiple Cox regression. The incidence rate of rheumatoid arthritis was 1.28 per 10,000 person-months in the H. pylori cohort, with a higher risk compared to the control group. In the < 30 years old subgroup, the risk was highest, especially in women < 30 years old with H. pylori infection. Patients with < 1 year follow-up showed 1.58 times higher susceptibility to rheumatoid arthritis. Individuals with follow-ups of 1-5 years and over 5 years demonstrated 1.43 and 1.44 times higher risks of rheumatoid arthritis, respectively. Our study showed H. pylori infection was associated with the development of rheumatoid arthritis. Clinicians should note higher risk, especially < 30 years old. More research needed to understand underlying mechanism.
59Detection of antibodies against synthetic peptides mimicking ureases fragments in sera of rheumatoid arthritis patients.PubMed
Iwona Konieczna, Marek Kwinkowski, Beata Kolesińska, et al.
Protein Pept Lett. 2012 Nov;19(11):1149-54. doi: 10.2174/092986612803217123.
Rheumatoid arthritis (RA) is a chronic disease with an autoimmunological background. RA is mostly characterized by systemic inflammation and injuries of synovial joints. There is a hypothesis that bacterial infections may be connected with development of the disease. It has been suggested that molecular mimicry between bacterial and human antigens may be one of possible mechanisms of RA development. One of potential antigens involved in this mechanism is urease - enzyme with high structural conservatism, occurring in pathogenic and commensal bacteria. We found that the level of antibodies against peptide mimicking urease "flap" region is significantly higher in sera from patients with rheumatoid arthritis in comparison with volunteer blood donor sera. We also observed that antibodies present in RA sera may bind not only specific peptide antigens but also peptides with a slightly different structure.
60Extragastric diseases and Helicobacter pylori.PubMed
Claire Roubaud Baudron, Francesco Franceschi, Nathalie Salles, et al.
Helicobacter. 2013 Sep;18 Suppl 1:44-51. doi: 10.1111/hel.12077.
In the last year, several diseases from outside of the gastrointestinal tract have been associated with Helicobacter pylori infection. Indeed, this bacterium produces a low-grade inflammatory state, induces molecular mimicry mechanisms, and interferes with the absorbance of nutrients and drugs possibly influencing the occurrence or the evolution of many diseases. In addition to its role in some hematologic conditions, such as immune thrombocytopenic purpura, idiopathic sideropenic anemia, and vitamin B12 deficiency, which were included in the current guidelines, several other conditions such as cardiovascular diseases, diabetes mellitus, hepatobiliary diseases, and neurologic disorders have also shown promising results.
61Helicobacter pylori and colorectal neoplasms: a concise review.PubMed
Luiz Gonzaga Vaz Coelho, Maria Clara Freitas Coelho
Arq Gastroenterol. 2021 Jan-Mar;58(1):114-119. doi: 10.1590/S0004-2803.202100000-19.
Helicobacter pylori is the main etiological agent of all malignant tumors caused by an infectious disease. It is a major, at times dominant, factor in the pathogenesis of a large spectrum of diseases such as acute and chronic gastritis, gastric and duodenal ulcers, gastric carcinoma, and lymphoma. Epidemiological and experimental studies suggest that H. pylori chronic infection may be related to different extragastric diseases, including colorectal neoplasms. This concise review aims to explore the association of H. pylori infection with colorectal cancer and adenoma, including the recent epidemiological findings, the diagnostic methods employed to detect H. pylori and virulent factors, and the potentially involved mechanisms. Furthermore, is attempted to establish the current data integration for causal inference using the Bradford-Hill causality criteria. The weak, although global, strength of the epidemiological positive association between H. pylori infection and colonic neoplasms associated to new mechanisms postulated to explain this interaction, including intestinal dysbiosis, should stimulate future studies. Prospective confirmatory studies to establish the role of H. pylori eradication in the process of carcinogenic transformation of the colonic epithelium may define its eventual role in the treatment and prevention of colonic neoplasms.
62Helicobacter pylori and extragastric diseases.PubMed
Francesco Franceschi, Antonio Gasbarrini
Best Pract Res Clin Gastroenterol. 2007;21(2):325-34. doi: 10.1016/j.bpg.2006.10.003.
Since the discovery of Helicobacter pylori, several studies have investigated the hypothetical role of this bacterium in various extragastric diseases, e.g. ischemic heart disease, idiopathic thrombocytopenic purpura, iron-deficiency anaemia, and other disorders. The majority of these studies are epidemiological or eradication trials, but there are also case reports and in-vitro studies. Idiopathic thromobocytopenic purpura is the disease that shows the strongest link with H. pylori infection. There is also evidence of a role of CagA-positive H. pylori infection in iron-deficiency anaemia and ischemic heart disease. The association between H. pylori infection and other extragastric diseases remains controversial, being mostly supported by 'case reports', small pilot studies, or just in-vitro data. Further studies are needed to identify whether there is any pathological implication for H. pylori infection in these diseases.
63Review: Extragastric diseases and Helicobacter pylori.PubMed
Rinaldo Pellicano, Gianluca Ianiro, Sharmila Fagoonee, et al.
Helicobacter. 2020 Sep;25 Suppl 1:e12741. doi: 10.1111/hel.12741.
The involvement of Helicobacter pylori infection in many extra-gastroduodenal manifestations remains a fascinating field of investigation. However, for several of these supposed associations, the potential pathogenic mechanism remains unclear. The present review highlights the main associations of H pylori with extra-gastroduodenal manifestations reported during the last year. We searched for the most relevant studies on this topic, published between April 2019 and March 2020, identified using the term "Helicobacter" in the MEDLINE/Pubmed database. Consistent data emerged from studies investigating metabolic syndrome and ischaemic cardiovascular diseases. Other reported fields of investigation were hepatology, especially focused on non-alcoholic steatohepatitis, neurology, including Parkinson's disease and Alzheimer's disease, as well as dermatology. Inflammatory bowel disease (IBD), that comprises Crohn's disease and ulcerative colitis, may originate from a dysregulation of the host's immune response to commensal bacteria in individuals with genetic predisposition. The reduction of biodiversity and other specific imbalances in the faecal microbiome composition of IBD patients compared to that of healthy controls support this hypothesis. In this context, an inverse correlation between H pylori infection and IBD prevalence has been confirmed. Similar results were found in patients with kidney diseases and allergic manifestations. There are indications of the possible involvement of H pylori infection in metabolic syndrome and ischaemic cardiovascular diseases. However, due to a series of factors linked to study designs and the multifactorial pathogenesis of some diseases, further studies are needed.
64Influence of Helicobacter pylori virulence factors CagA and VacA on pathogenesis of gastrointestinal disorders.PubMed
Shima Nejati, Ahmad Karkhah, Hossein Darvish, et al.
Microb Pathog. 2018 Apr;117:43-48. doi: 10.1016/j.micpath.2018.02.016. Epub 2018 Feb 9.
Helicobacter Pylori (H. pylori) is a gram-negative bacteria infecting numerous people all over the world. It has been established that H. pylori play an important role in pathogenesis of gastritis, peptic ulcer and gastric cancer. Pathogenic features of this bacterium are mainly attributes to the existence of pathogenic islands (PAI) genes. The most known genes in these islands are cytotoxin-associated gene A (CagA) and vacuolating cytotoxin gene (VacA). Most studies demonstrated various frequency of CagA and VacA in patient with peptic ulcer or gastritis in different countries. This variation in CagA and VacA frequency may be due to the capability of this bacterium to be genetically versatile and can alter the expression of these genes with geographic diversity. Although H. pylori infection is not usually associated with any clinical symptoms, but sometimes leads to inflammation in gastrointestinal system and resulted in peptic ulcer and gastric cancer. In this regard, this review will illustrate the importance of Helicobacter pylori in pathogenesis of gastrointestinal disorders with focusing on CagA and VacA virulence factors.
66Pathogenesis of Helicobacter pylori infection.PubMed
Vania Camilo, Toshiro Sugiyama, Eliette Touati
Helicobacter. 2017 Sep;22 Suppl 1. doi: 10.1111/hel.12405.
Helicobacter pylori is responsible for the most commonly found infection in the world's population. It is the major risk factor for gastric cancer development. Numerous studies published over the last year provide new insights into the strategies employed by H. pylori to adapt to the extreme acidic conditions of the gastric environment, to establish persistent infection and to deregulate host functions, leading to gastric pathogenesis and cancer. In this review, we report recent data on the mechanisms involved in chemotaxis, on the essential role of nickel in acid resistance and gastric colonization, on the importance of adhesins and Hop proteins and on the role of CagPAI-components and CagA. Among the host functions, a special focus has been made on the escape from immune response, the ability of bacteria to induce genetic instability and modulate telomeres, the mechanism of autophagy and the deregulation of micro RNAs.
67Activity and Functional Importance of Helicobacter pylori Virulence Factors.PubMed
Dionyssios Sgouras, Nicole Tegtmeyer, Silja Wessler
Adv Exp Med Biol. 2019;1149:35-56. doi: 10.1007/5584_2019_358.
Helicobacter pylori is a very successful Gram-negative pathogen colonizing the stomach of humans worldwide. Infections with this bacterium can generate pathologies ranging from chronic gastritis and peptic ulceration to gastric cancer. The best characterized H. pylori virulence factors that cause direct cell damage include an effector protein encoded by the cytotoxin-associated gene A (CagA), a type IV secretion system (T4SS) encoded in the cag-pathogenicity island (cag PAI), vacuolating cytotoxin A (VacA), γ-glutamyl transpeptidase (GGT), high temperature requirement A (HtrA, a serine protease) and cholesterol glycosyl-transferase (CGT). Since these H. pylori factors are either surface-exposed, secreted or translocated, they can directly interact with host cell molecules and are able to hijack cellular functions. Studies on these bacterial factors have progressed substantially in recent years. Here, we review the current status in the characterization of signaling cascades by these factors in vivo and in vitro, which comprise the disruption of cell-to-cell junctions, induction of membrane rearrangements, cytoskeletal dynamics, proliferative, pro-inflammatory, as well as, pro-apoptotic and anti-apoptotic responses or immune evasion. The impact of these signal transduction modules in the pathogenesis of H. pylori infections is discussed.
68Helicobacter pylori Outer Membrane Protein-Related Pathogenesis.PubMed
Yuichi Matsuo, Yasutoshi Kido, Yoshio Yamaoka
Toxins (Basel). 2017 Mar 11;9(3):101. doi: 10.3390/toxins9030101.
colonizes the human stomach and induces inflammation, and in some cases persistent infection can result in gastric cancer. Attachment to the gastric mucosa is the first step in establishing bacterial colonization, and outer membrane proteins (OMPs) play a pivotal role in binding to human cells. Some OMP interaction molecules are known in , and their associated host cell responses have been gradually clarified. Many studies have demonstrated that OMPs are essential to CagA translocation into gastric cells via the Type IV secretion system of . This review summarizes the mechanisms through which utilizes OMPs to colonize the human stomach and how OMPs cooperate with the Type IV secretion system.
69Cancer-associated SNPs in bacteria: lessons from Helicobacter pylori.PubMed
Bodo Linz, Heinrich Sticht, Nicole Tegtmeyer, et al.
Trends Microbiol. 2024 Sep;32(9):847-857. doi: 10.1016/j.tim.2024.02.001. Epub 2024 Mar 13.
Several single-nucleotide polymorphisms (SNPs) in human chromosomes are known to predispose to cancer. However, cancer-associated SNPs in bacterial pathogens were unknown until discovered in the stomach pathogen Helicobacter pylori. Those include an alanine-threonine polymorphism in the EPIYA-B phosphorylation motif of the injected effector protein CagA that affects cancer risk by modifying inflammatory responses and loss of host cell polarity. A serine-to-leucine change in serine protease HtrA is associated with boosted proteolytic cleavage of epithelial junction proteins and introduction of DNA double-strand breaks (DSBs) in host chromosomes, which co-operatively elicit malignant alterations. In addition, H. pylori genome-wide association studies (GWAS) identified several other SNPs potentially associated with increased gastric cancer (GC) risk. Here we discuss the clinical importance, evolutionary origin, and functional advantage of the H. pylori SNPs. These exciting new data highlight cancer-associated SNPs in bacteria, which should be explored in more detail in future studies.
70H. pylori-induced NF-κB-PIEZO1-YAP1-CTGF axis drives gastric cancer progression and cancer-associated fibroblast-mediated tumour microenvironment remodelling.PubMed
Bonan Chen, Xiaoli Liu, Peiyao Yu, et al.
Clin Transl Med. 2023 Nov;13(11):e1481. doi: 10.1002/ctm2.1481.
BACKGROUND: Gastric cancer (GC) is one of the most common tumours in East Asia countries and is associated with Helicobacter pylori infection. H. pylori utilizes virulence factors, CagA and VacA, to up-regulate pro-inflammatory cytokines and activate NF-κB signaling. Meanwhile, the PIEZO1 upregulation and cancer-associated fibroblast (CAF) enrichment were found in GC progression. However, the mechanisms of PIEZO1 upregulation and its involvement in GC progression have not been fully elucidated. METHODS: The CAF enrichment and clinical significance were investigated in animal models and primary samples. The expression of NF-κB and PIEZO1 in GC was confirmed by immunohistochemistry staining, and expression correlation was analysed in multiple GC datasets. GSEA and Western blot analysis revealed the YAP1-CTGF axis regulation by PIEZO1. The stimulatory effects of CTGF on CAFs were validated by the co-culture system and animal studies. Patient-derived organoid and peritoneal dissemination models were employed to confirm the role of the PIEZO1-YAP1-CTGF cascade in GC. RESULTS: Both CAF signature and PIEZO1 were positively correlated with H. pylori infection. PIEZO1, a mechanosensor, was confirmed as a direct downstream of NF-κB to promote the transformation from intestinal metaplasia to GC. Mechanistic studies revealed that PIEZO1 transduced the oncogenic signal from NF-κB into YAP1 signaling, a well-documented oncogenic pathway in GC progression. PIEZO1 expression was positively correlated with the YAP1 signature (CTGF, CYR61, and c-Myc, etc.) in primary samples. The secreted CTGF by cancer cells stimulated the CAF infiltration to form a stiffened collagen-enrichment microenvironment, thus activating PIEZO1 to form a positive feedback loop. Both PIEZO1 depletion by shRNA and CTGF inhibition by Procyanidin C1 enhanced the efficacy of 5-FU in suppressing the GC cell peritoneal metastasis. CONCLUSION: This study elucidates a novel driving PIEZO1-YAP1-CTGF force, which opens a novel therapeutic avenue to block the transformation from precancerous lesions to GC. H. pylori-NF-κB activates the PIEZO1-YAP1-CTGF axis to remodel the GC microenvironment by promoting CAF infiltration. Targeting PIEZO1-YAP1-CTGF plus chemotherapy might serve as a potential therapeutic option to block GC progression and peritoneal metastasis.
71Helicobacter pylori pathogenicity and primary antimicrobial resistance in Northern Spain.PubMed
María Fernández-Reyes, Esther Tamayo, Diana Rojas-Rengifo, et al.
Eur J Clin Invest. 2019 Aug;49(8):e13150. doi: 10.1111/eci.13150. Epub 2019 Jul 1.
BACKGROUND: Helicobacter pylori infection is associated with chronic gastritis, ulcers and gastric cancer. Antimicrobial resistance has increased worldwide affecting the efficacy of current treatments. Most guidelines recommend implementation of regional surveillance of primary antibiotic resistance of H pylori. Only a fraction of individuals infected with H pylori develop gastric diseases which are related to virulence factors of the bacteria. The aims of the study were to determine the primary antimicrobial resistance rates of H pylori and to know the virulence factors prevalence of strains circulating in Southern Europe. MATERIALS AND METHODS: Susceptibility testing by Etest to clarithromycin, levofloxacin, metronidazole, amoxicillin and tetracycline was performed in 102 isolates (99 naïve patients). The prevalence of virulence factors (cagA, vacA, oipA, babA and dupA) was evaluated in 102 H pylori isolates from patients with mild-disease symptoms and in 22 isolates from patients with severe-disease symptoms. RESULTS: Primary resistance rates were 12.1% to clarithromycin, 13.1% to levofloxacin, 24.2% to metronidazole and 0% to amoxicillin and tetracycline. Combined resistance to clarithromycin and levofloxacin was 3% and to clarithromycin and metronidazole 4%. Prevalence of virulence factors in the mild- and severe-disease group was 35.3% and 81.8% for cagA, 20.6% and 54.5% for cagA/vacAs1m1, 94.1% and 95.4% for babA2, 78.4% and 100% for oipA and 30.4% and 18.2% for dupA. CONCLUSIONS: Primary antimicrobial resistance rates were under 15% for clarithromycin and levofloxacin. The prevalence of H pylori carrying the virulent genotype cagA/vacAs1m1 was higher than 20% in the mild-disease and 54% in the severe-disease symptom group.
72Virulence gene polymorphisms in Shandong Helicobacter pylori strains and their relevance to gastric cancer.PubMed
Zhijing Xue, Weijia Li, Hailing Ding, et al.
PLoS One. 2024 Sep 9;19(9):e0309844. doi: 10.1371/journal.pone.0309844. eCollection 2024.
BACKGROUND: Helicobacter pylori (H. pylori) virulence factors, particularly the cagA and vacA genotypes, play important roles in the pathogenic process of gastrointestinal disease. METHODS: The cagA and vacA genotypes of 87 H. pylori strains were determined by PCR and sequencing. The EPIYA and CM motif patterns were analyzed and related to clinical outcomes. We examined the associations between the virulence genes of H. pylori and gastrointestinal diseases in Shandong, and the results were analyzed via the chi-square test and logistic regression model. RESULTS: Overall, 76 (87.36%) of the strains carried the East Asian-type CagA, with the ABD types being the most prevalent (90.79%). However, no significant differences were observed among the different clinical outcomes. The analysis of CagA sequence types revealed 8 distinct types, encompassing 250 EPIYA motifs, including 4 types of EPIYA or EPIYA-like sequences. Additionally, 28 CM motifs were identified, with the most prevalent patterns being E (66.67%), D (16.09%), and W-W (5.75%). Notably, a significant association was discovered between strains with GC and the CM motif pattern D (P < 0.01). With respect to the vacA genotypes, the strains were identified as s1, s2, m1, m2, i1, i2, d1, d2, c1, and c2 in 87 (100%), 0 (0), 26 (29.89%), 61 (70.11%), 73 (83.91%), 14 (16.09%), 76 (87.36%), 11 (12.64%), 18 (20.69%), and 69 (79.31%), respectively. Specifically, the vacA m1 and c1 genotypes presented a significantly greater prevalence in strains from GC compared to CG (P < 0.05). Following adjustment for age and sex, the vacA c1 genotype demonstrated a notable association with GC (OR = 5.174; 95% CI, 1.402-20.810; P = 0.012). This association was both independent of and more pronounced than the correlations between vacA m1 and GC. CONCLUSIONS: CagA proteins possessing CM motif pattern D were more frequently observed in patients with GC (P < 0.01), implying a potentially higher virulence of CM motif pattern D than the other CM motif patterns. Moreover, a strong positive association was identified between the vacA c1 genotype and GC, indicating that the vacA c1 genotype is a robust risk indicator for GC among male patients aged ≥55 years in Shandong.
73AUF1-mediated inhibition of autophagic lysosomal degradation contributes to CagA stability and -induced inflammation.PubMed
Huiling Zheng, Ting Zhang, Jing Zhang, et al.
Gut Microbes. 2024 Jan-Dec;16(1):2382766. doi: 10.1080/19490976.2024.2382766. Epub 2024 Jul 28.
CagA, a virulence factor of (), is known to drive inflammation in gastric epithelial cells and is typically degraded through autophagy. However, the molecular mechanism by which CagA evades autophagy-mediated degradation remains elusive. This study found that inhibits autophagic flux by upregulating the expression of AU-rich element RNA-binding factor 1 (AUF1). We confirmed that AUF1 does not affect autophagy initiation but instead hampers lysosomal clearance, as evidenced by treatments with 3-MA, CQ and BafA1. Upregulated AUF1 stabilizes CagA protein levels by inhibiting the autolysosomal degradation of intracellular CagA in -infected gastric epithelial cells. Knocking down AUF1 promotes CagA degradation, an effect that can be reversed by the lysosome inhibitor BafA1 and CQ. Transcriptome analysis of AUF1-knockdown gastric epithelial cells infected with indicated that AUF1 regulates the expression of lysosomal-associated hydrolase genes, specifically CTSD, to inhibit autolysosomal degradation. Moreover, we observed that knockdown of AUF1 enhanced the stability of CTSD mRNA and identified AUF1 binding to the 3'UTR region of CTSD mRNA. AUF1-mediated downregulation of CTSD expression contributes to CagA stability, and AUF1 overexpression leads to an increase in CagA levels in exosomes, thus promoting extracellular inflammation. In clinical gastric mucosa, the expression of AUF1 and its cytoplasmic translocation are associated with -associated gastritis, with CagA being necessary for the translocation of AUF1 into the cytoplasm. Our findings suggest that AUF1 is a novel host-positive regulator of CagA, and dysregulation of AUF1 expression increases the risk of -associated gastritis.
74A single-nucleotide polymorphism in Helicobacter pylori promotes gastric cancer development.PubMed
Irshad Sharafutdinov, Nicole Tegtmeyer, Bodo Linz, et al.
Cell Host Microbe. 2023 Aug 9;31(8):1345-1358.e6. doi: 10.1016/j.chom.2023.06.016. Epub 2023 Jul 24.
Single-nucleotide polymorphisms (SNPs) in various human genes are key factors in carcinogenesis. However, whether SNPs in bacterial pathogens are similarly crucial in cancer development is unknown. Here, we analyzed 1,043 genomes of the stomach pathogen Helicobacter pylori and pinpointed a SNP in the serine protease HtrA (position serine/leucine 171) that significantly correlates with gastric cancer. Our functional studies reveal that the 171S-to-171L mutation triggers HtrA trimer formation and enhances proteolytic activity and cleavage of epithelial junction proteins occludin and tumor-suppressor E-cadherin. 171L-type HtrA, but not 171S-HtrA-possessing H. pylori, inflicts severe epithelial damage, enhances injection of oncoprotein CagA into epithelial cells, increases NF-κB-mediated inflammation and cell proliferation through nuclear accumulation of β-catenin, and promotes host DNA double-strand breaks, collectively triggering malignant changes. These findings highlight the 171S/L HtrA mutation as a unique bacterial cancer-associated SNP and as a potential biomarker for risk predictions in H. pylori infections.
75Role of Flagella in the Pathogenesis of Helicobacter pylori.PubMed
Haiying Gu
Curr Microbiol. 2017 Jul;74(7):863-869. doi: 10.1007/s00284-017-1256-4. Epub 2017 Apr 26.
This review aimed to investigate the role of Helicobacter pylori flagella on the pathogenicity of this bacterium in humans. Helicobacter pylori is a flagellated pathogen that colonizes the human gastroduodenal mucosa and produces inflammation, and is responsible for gastrointestinal disease. Its pathogenesis is attributed to colonization and virulence factors. The primary function of H. pylori flagella is to provide motility. We believe that H. pylori flagella play an important role in the colonization of the gastrointestinal mucosa. Therefore, we reviewed previous studies on flagellar morphology and motility in order to explore the relationship between H. pylori flagella and pathogenicity. Further investigation is required to confirm the association between flagella and pathogenicity in H. pylori.
76Associations between biofilm formation and virulence factors among clinical Helicobacter pylori isolates.PubMed
Mariam Ashkar Daw, Maya Azrad, Avi Peretz
Microb Pathog. 2024 Nov;196:106977. doi: 10.1016/j.micpath.2024.106977. Epub 2024 Sep 23.
INTRODUCTION: Helicobacter pylori (H. pylori) causes several gastrointestinal diseases. Its virulence factors contributing to disease development include biofilm formation, cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA) proteins that induce host tissue damage. In addition, urease activity enables H. pylori growth in the gastric acidic environment. This work aimed to characterize bacterial factors associated with biofilm production among 89 clinical H. pylori isolates, collected from patient gastric biopsies. METHODS: Biofilm production was detected using the crystal violet method. PCR was performed to determine vacA genotype (s1m1, s1m2, s2m1 and s2m2) and cagA gene presence. Urease activity was measured via the phenol red method. Susceptibility to six antibiotics was assessed by the Etest method. RESULTS: Most H. pylori isolates produced biofilm. No association was found between biofilm-formation capacity and cagA presence or vacA genotype. Urease activity levels varied across isolates; no association was found between biofilm-formation and urease activity. Clarithromycin resistance was measured in 49 % of the isolates. Isolates susceptible to tetracycline were more commonly strong biofilm producers. In contrast, a significantly higher rate of strong biofilm producers was observed among resistant isolates to amoxicillin, levofloxacin and rifampicin, compared to susceptible isolates. Non-biofilm producers were more common among isolates sensitive to rifampicin and metronidazole, compared to resistant isolates. CONCLUSIONS: Further studies are needed to understand the factors that regulate biofilm production in order to search for treatments for H. pylori biofilm destruction.
77Primary Antibiotic Resistance of Helicobacter pylori in China.PubMed
Yi Hu, Yin Zhu, Nong-Hua Lu
Dig Dis Sci. 2017 May;62(5):1146-1154. doi: 10.1007/s10620-017-4536-8. Epub 2017 Mar 17.
BACKGROUND AND AIMS: Antibiotic resistance is the most important factor leading to the failure of eradication regimens; thus, it is important to obtain regional antibiotic resistance information. This review focuses on the prevalence of Helicobacter pylori primary resistance to clarithromycin, metronidazole, amoxicillin, levofloxacin, tetracycline, and furazolidone in China. METHODS: We searched the PubMed, EMBASE, the China National Knowledge Infrastructure, and Chinese Biomedical databases from the earliest date of each database to October 2016. The search terms included the following: H. pylori, antibiotic (including clarithromycin, metronidazole, amoxicillin, levofloxacin, tetracycline, and furazolidone) resistance with or without China or different regions of China. The data analysis was performed using MedCalc 15.2.2. Each article was weighted according to the number of isolated H. pylori strains. A pooled proportion analysis was performed. RESULTS: Twenty-three studies (14 studies in English and 9 in Chinese) were included in this review. A total of 6274, 6418, 3921, 5468, 2802, and 275 H. pylori strains were included in this review to evaluate the prevalence of H. pylori primary resistance to clarithromycin, metronidazole, levofloxacin, amoxicillin, tetracycline, and furazolidone, respectively. Overall, the primary resistance rates of clarithromycin, metronidazole, levofloxacin, amoxicillin, tetracycline, and furazolidone were 28.9, 63.8, 28.0, 3.1, 3.9, and 1.7%, respectively. CONCLUSIONS: In China, the prevalence of H. pylori primary resistance to clarithromycin, metronidazole, and levofloxacin was high and increased over time, whereas the resistance rates to amoxicillin, tetracycline, and furazolidone were low and stable over time.
78Primary Antibiotic Resistance of in Different Regions of China: A Systematic Review and Meta-Analysis.PubMed
Jinnan Chen, Puheng Li, Yu Huang, et al.
Pathogens. 2022 Jul 12;11(7):786. doi: 10.3390/pathogens11070786.
AIM: Understanding the prevalence of antibiotic resistance can provide reliable information for selecting treatment options. The goal of this meta-analysis was to observe the primary antibiotic resistance of () in different regions and time periods of China. METHOD: We searched PubMed, EMBASE, Chinese Biomedical databases and the China National Knowledge Infrastructure from inception to 20 February 2022. Data on the prevalence of primary resistance at various time points were included. A random-effect model was established to calculate the pooled antibiotic resistance. RESULTS: In total, 2150 articles were searched, with 70 meeting the inclusion criteria. The resistance to clarithromycin, metronidazole, levofloxacin amoxicillin, tetracycline and furazolidone in 2016-2020 were 34% (95% CI: 30-39%), 78% (95% CI: 73-84%), 35% (95% CI: 30-40%), 3% (95% CI: 1-5%), 2% (95%CI: 1-4%) and 1% (95% CI: 0-4%), respectively. Clarithromycin showed regional difference, as the resistance was higher in northern (37%, 95% CI: 32-41%) and western China (35%, 95% CI: 17-54%) than that in southern (24%, 95% CI: 17-32%) and eastern China (24%, 95% CI: 20-28%). CONCLUSION: The resistance of to clarithromycin and metronidazole was high and increased over time, whereas resistance to levofloxacin, amoxicillin, tetracycline and furazolidone remained stable.
79Primary antibiotic resistance of Helicobacter pylori in the Asia-Pacific region between 1990 and 2022: an updated systematic review and meta-analysis.PubMed
Tzu-Chan Hong, Emad M El-Omar, Yu-Ting Kuo, et al.
Lancet Gastroenterol Hepatol. 2024 Jan;9(1):56-67. doi: 10.1016/S2468-1253(23)00281-9. Epub 2023 Nov 14.
BACKGROUND: We previously showed rising primary antibiotic resistance of Helicobacter pylori during 1990-2015 in the Asia-Pacific region. However, whether primary antibiotic resistance continues to rise is unknown. Therefore, we aimed to assess the latest prevalence of H pylori antibiotic resistance in this region. METHODS: We did an updated systematic review and meta-analysis of observational studies and randomised controlled trials published in PubMed, Embase, and Cochrane Library between Jan 1, 1990, and July 12, 2023. Studies investigating primary H pylori resistance to clarithromycin, metronidazole, levofloxacin, amoxicillin, or tetracycline in individuals naive to eradication therapy in the Asia-Pacific region (as defined by the UN geoscheme) were eligible for inclusion. There were no language restrictions. Studies that focused on specific subpopulations (eg, children) were excluded. Using a standardised extraction form, two authors independently reviewed and extracted summary data from all eligible articles. The updated prevalence of antibiotic resistance was generated by meta-analysis under a random-effects model and subgroup analyses were done by countries and periods of study. Between-study variability was assessed by use of I. The study is registered in PROSPERO, CRD42022339956. FINDINGS: A total of 351 studies, including 175 new studies and 176 studies from our previous analysis, were included in this meta-analysis. The overall prevalence of primary antibiotic resistance of H pylori between 1990 and 2022 was 22% (95% CI 20-23; I=96%) for clarithromycin, 52% (49-55; I=99%) for metronidazole, 26% (24-29; I=96%) for levofloxacin, 4% (3-5; I=95%) for tetracycline, and 4% (3-5; I=95%) for amoxicillin. Prevalence varied considerably between countries and across study periods. From 1990 to 2022, the prevalence of primary resistance increased for clarithromycin, metronidazole, and levofloxacin but remained stable for amoxicillin and tetracycline. The latest primary resistance prevalences were 30% (95% CI 28-33; I=93%) for clarithromycin, 61% (55-66; I=99%) for metronidazole, 35% (31-39; I=95%) for levofloxacin, 4% (2-6; I=96%) for tetracycline, and 6% (4-8; I=96%) for amoxicillin in the Asia-Pacific region. INTERPRETATION: Treatment guidelines should be adapted in response to the rising primary resistance of key antibiotics for H pylori eradication. A global policy to control and monitor the antibiotic resistance of H pylori is urgently needed. FUNDING: Ministry of Health and Welfare of Taiwan, National Science and Technology Council of Taiwan, and National Taiwan University. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.
80Primary antibiotic resistance in Helicobacter pylori in China: a systematic review and meta-analysis.PubMed
Yuxiang Wang, Jinran Du, Dayan Zhang, et al.
J Glob Antimicrob Resist. 2023 Sep;34:30-38. doi: 10.1016/j.jgar.2023.05.014. Epub 2023 Jun 12.
OBJECTIVES: The incidence of Helicobacter pylori (HP) is 25-50% in developed countries and 80% in developing countries, including 56.2% in China. However, antibiotic resistance of HP is a threat to HP control. The purpose of this study was to comprehensively evaluate primary drug resistance of HP in China. METHODS: The full text of reports of the primary antibiotic resistance prevalence of HP was obtained from multiple databases (PubMed, Web of Science, Evimed, Cochrane Library, and China National Knowledge Internet). Review Manager 5.2 was adopted for meta-analysis, sensitivity analysis, and bias analysis. The Newcastle-Ottawa Scale was used to assess the article quality. RESULTS: In total, 38804 HP samples from 22 trials were extracted. The results suggested that the overall prevalence of amoxicillin, clarithromycin, metronidazole, and levofloxacin resistance among HP in adults was as follows: mean difference (MD) = 1.35%, 95% confidence interval (CI) [1.03%, 1.68%]; MD = 23.76%, 95% CI [20.23%, 27.3%]; MD = 69.32%, 95% CI [64.85%, 73.8%]; and MD = 29.45%, 95% CI [4.90, 176.96], respectively. From the results of sensitivity and publication bias, we find that these results are robust and had little publication bias. CONCLUSION: Our research showed that in China, the prevalence of HP resistance to primary antibiotics warrants attention, especially with regard to metronidazole, levofloxacin, and clarithromycin.
81Antibiotic resistance of Helicobacter pylori in Mainland China: A focus on geographic differences through systematic review and meta-analysis.PubMed
Shuyan Zeng, Qingzhou Kong, Xiaoqi Wu, et al.
Int J Antimicrob Agents. 2024 Nov;64(5):107325. doi: 10.1016/j.ijantimicag.2024.107325. Epub 2024 Sep 6.
BACKGROUND: Empirical treatment needs to be supported by regional data, but knowledge of interregional differences is currently lacking in China. This study aimed to summarize and map the primary and secondary antibiotic resistance of Helicobacter pylori in different regions of mainland China. METHODS: PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure and Wanfang databases were systematically reviewed for studies published between 1 January 2000 and 15 July 2023. Data related to primary and secondary H. pylori antibiotic resistance rates were included. Random-effects models were used to synthesize the pooled resistance rates. RESULTS: Ultimately, 74 studies were included in the final analysis. A total of 16 provinces reported resistance data. The overall resistance rates of H. pylori in mainland China were 30.72% (95% CI 27.53%-33.99%) to clarithromycin, 70.14% (95% CI 29.53%-37.46%) to metronidazole and 32.98% (95% CI 28.73%-37.37%) to levofloxacin; for amoxicillin, tetracycline, and furazolidone, the rates were 2.41% (95% CI 1.43%-3.60%), 2.53% (95% CI 1.19%-4.28%) and 1.54% (95% CI 0.28%-3.62%), respectively. Spatial and temporal differences were observed. The resistance rates increased after treatment failure; however, secondary resistance to amoxicillin, tetracycline and furazolidone were still low across the vast majority of study regions. CONCLUSION: Surveillance of the updated prevalence of antibiotic resistance of H. pylori for different regions is warranted, which should factor into clinical decision making and guideline recommendations.
82Linolenic Acid-Metronidazole: a Compound Relieving Drug Resistance and Inhibiting Helicobacter pylori.PubMed
Yuan-Yuan Dai, Chun Qin, Gan-Rong Huang, et al.
Antimicrob Agents Chemother. 2022 Jul 19;66(7):e0007322. doi: 10.1128/aac.00073-22. Epub 2022 Jun 27.
Metronidazole (Met) is the first choice for treating Helicobacter pylori (). However, is easy to resistant, making Met unable to be widely used. How to overcome 's Met resistance is still an issue. In this study, Met was used as the primary raw material with linolenic acid to prepare a novel compound-linolenic acid-metronidazole (Lla-Met). The MIC, minimum bactericidal concentration (MBC), colonization amount of in gastric mucosa, etc., were evaluated, respectively. Lla-Met was successfully prepared by the detection of nuclear magnetic resonance, etc., and its MIC and MBC to were 2~4 μg/mL, 8~16 μg/mL. Moreover, experiments, Lla-Met significantly reduced the colonization of drug-resistant in gastric mucosa. In the toxicity test, Lla-Met inhibited rate to GES-1 and BGC823 cells were 15% at 128 μg/mL; the mice were administered 10 times treatment Lla-Met treatment (240 mg/kg), have no difference significant injuries were found in their stomach, liver, spleen, kidney, and weight. In addition, G27 continued for 18 days with sub-Lla-Met concentration, G27 did not show drug resistance to Lla-Met; Lla-Met did not exert an effect on non- species with 128 μg/mL; Compared with a neutral environment, when the acid concentration is 3.0, Lla-Met is not decomposed and has better stability. Conclusion: Lla-Met, a newly prepared compound, has relatively well antibacterial of Met-resistant and sensitive , with a capability of overcoming the metronidazole resistance of
83Antibiotic resistance of and related risk factors in Hunan Province: A multicenter study.PubMed
Jie Xie, Ming-Lin Zhang, Min Guo, et al.
World J Gastroenterol. 2025 Mar 28;31(12):104835. doi: 10.3748/wjg.v31.i12.104835.
BACKGROUND: Antibiotic resistance is a key factor influencing the treatment outcomes of () infection. The antibiotic resistance spectrum of varies in different regions. We investigated the current status of antibiotic resistance of in Hunan Province and analyzed the factors related to such resistance to provide strategies for the accurate clinical treatment of infection. AIM: To understand the antibiotic resistance of in Hunan Province and provide guidance for the clinical treatment of infection. METHODS: This study selected patients who underwent gastroscopy in five hospitals in Hunan Province from April 2022 to April 2023. The sensitivity of to clarithromycin, levofloxacin, metronidazole, amoxicillin, furazolidone, and tetracycline was detected using the Agar dilution method. RESULTS: strains from a total of 566 patients were isolated and identified. The resistance rates of strains to clarithromycin, levofloxacin, metronidazole, amoxicillin, furazolidone, and tetracycline were 49.2%, 37.8%, 76.1%, 2.3%, 1.4%, and 0.7%, respectively. The resistance rates to clarithromycin, levofloxacin, and metronidazole were high in the four regions of Hunan Province, and the overall resistance rates in central Hunan Province were higher than those in other regions. The resistance rates of strains to clarithromycin and levofloxacin were significantly different among the different age groups ( < 0.05), with the elderly group having a higher resistance rate than the young group. The resistance rate of strains to clarithromycin was greater in patients with atrophic gastritis, and the resistance rate to levofloxacin was the lowest in patients with peptic ulcers. CONCLUSION: The resistance rate of to amoxicillin, clarithromycin, and metronidazole is high in Hunan Province. Age, stomach disease, and reinfection may affect the antibiotic resistance of .
84Antibiotic Resistance of in Patients with Peptic Ulcer.PubMed
Thanh Binh Vu, Thi Nhu Quynh Tran, Thi Quynh Anh Tran, et al.
Medicina (Kaunas). 2022 Dec 20;59(1):6. doi: 10.3390/medicina59010006.
: To determine the antibiotic resistance rate of among patients with peptic ulcer. : A cross-sectional monocentric study was conducted from January to December 2021 among patients aged from 16 years with gastrointestinal symptoms and esophagogastroduodenoscopy. Gastric mucosa biopsies were collected at the edges of the ulcer or at lesion sites for culture. Five antibiotics (amoxicillin (AMX), clarithromycin (CLR), metronidazole (MTZ), levofloxacin (LEV), and tetracycline (TET)) were selected for antibiotic susceptibility testing. : One hundred and twenty-five patients were included, and the sex ratio was 0.6. Their mean age was 47.3 ± 14.2 years. All of the participants had gastritis, and 24.0% had duodenitis. A total of 21.6% of patients had a duodenal ulcer, and 12.8% had an antral ulcer. A total of 40 specimens have grown in culture. The proportion of resistance to AMX, CLR, MTZ, LEV, and TET was 27.5%, 50%, 67.5%, 35%, and 5%, respectively. The proportion of multidrug resistance was 22.5%. The proportion of double resistance to AMX + CLR was 20.0%, AMX + MTZ was 15.0%, AMX + LEV was 2.5%, CLR + MTZ was 32.5%, and TET + MTZ was 5.0%. : Our research results show that the treatment with MTX-TET or LVX-AMOX has the highest sensitivity rate. Therefore, practitioners should refer to these regimes to eradicate in patients with gastric and duodenal ulcers. The reports on eradication from different geographic areas show heterogeneous results. Therefore, continuous monitoring of antibiotic resistance of in each population is very important. Having evidence helps clinicians to treat patients most effectively, reduce treatment costs, and limit the rate of antibiotic resistance.
85Helicobacter pylori: Multiple resistance in patients from Bogotá, Colombia.PubMed
Azucena Arévalo, William Alberto Otero, Alba Alicia Trespalacios
Biomedica. 2019 May 1;39(s1):125-134. doi: 10.7705/biomedica.v39i3.4437.
Introduction: The main cause for Helicobacter pylori infection treatment failure is antibiotic resistance, where clarithromycin and metronidazole play the main role. In Colombia, primary resistance as a consequence of the use of these two antibiotics and excessive levofloxacin use is above the accepted limit (13.6%, 83%, and 16%, respectively). Despite this fact, empirical therapies that include the combination of these antibiotics are used in patients with previous therapeutic failure. Objective: To determine antibiotic resistance in patients previously treated for H. pylori in Bogotá, Colombia. Materials and methods: We conducted a descriptive study that included ten isolates obtained from five patients with three or four previous failed treatments for H. pylori. Antibiotic resistance to amoxicillin, clarithromycin, levofloxacin, and metronidazole was investigated by agar dilution and confirmed by DNA sequencing (Magrogen, Korea). Results: Eight isolates were resistant to two or more antibiotics. All isolates were resistant to levofloxacin. Susceptibility patterns in isolates from the gastric antrum and the body of the stomach were different in three patients. Conclusion: As far as we know, this is the first evidence of multiple H. pylori resistance in Colombia in previously treated patients. Results demonstrated the consequences of using an ineffective antibiotic scheme and the need to assess antibiotic susceptibility in different anatomical sites of the stomach. The consequences of multiple resistance decrease possible antibiotic effectiveness to eradicate H. pylori in the future.
86Genomic insights into the antimicrobial resistance and virulence of Helicobacter pylori isolates from gastritis patients in Pereira, Colombia.PubMed
Adalucy Alvarez-Aldana, Odion O Ikhimiukor, Yina Marcela Guaca-González, et al.
BMC Genomics. 2024 Sep 9;25(1):843. doi: 10.1186/s12864-024-10749-6.
BACKGROUND: Helicobacter pylori infects the stomach and/or small intestines in more than half of the human population. Infection with H. pylori is the most common cause of chronic gastritis, which can lead to more severe gastroduodenal pathologies such as peptic ulcer, mucosa-associated lymphoid tissue lymphoma, and gastric cancer. H. pylori infection is particularly concerning in Colombia in South America, where > 80% of the population is estimated to be infected with H. pylori and the rate of stomach cancer is one of the highest in the continent. RESULTS: We compared the antimicrobial susceptibility profiles and short-read genome sequences of five H. pylori isolates obtained from patients diagnosed with gastritis of varying severity (chronic gastritis, antral erosive gastritis, superficial gastritis) in Pereira, Colombia sampled in 2015. Antimicrobial susceptibility tests revealed the isolates to be resistant to at least one of the five antimicrobials tested: four isolates were resistant to metronidazole, two to clarithromycin, two to levofloxacin, and one to rifampin. All isolates were susceptible to tetracycline and amoxicillin. Comparative genome analyses revealed the presence of genes associated with efflux pump, restriction modification systems, phages and insertion sequences, and virulence genes including the cytotoxin genes cagA and vacA. The five genomes represent three novel sequence types. In the context of the Colombian and global populations, the five H. pylori isolates from Pereira were phylogenetically distant to each other but were closely related to other lineages circulating in the country. CONCLUSIONS: H. pylori from gastritis of different severity varied in their antimicrobial susceptibility profiles and genome content. This knowledge will be useful in implementing appropriate eradication treatment regimens for specific types of gastritis. Understanding the genetic and phenotypic heterogeneity in H. pylori across the geographical landscape is critical in informing health policies for effective disease prevention and management that is most effective at local and country-wide scales. This is especially important in Colombia and other South American countries that are poorly represented in global genomic surveillance studies of bacterial pathogens.
87Helicobacter pylori Infection and Dietary Factors Act Synergistically to Promote Gastric Cancer.PubMed
Negin Raei, Bahador Behrouz, Saber Zahri, et al.
Asian Pac J Cancer Prev. 2016;17(3):917-21. doi: 10.7314/apjcp.2016.17.3.917.
However, the incidence of gastric cancer (GC) has been decreased in past decades; GC is the second cause of cancer related death in the world. Evidence has illustrated that several factors including Helicobacter pylori (H. pylori) infection, host genetics, and environmental factors (smoking and particularly diet) may play a crucial role in gastric carcinogenesis. It has been demonstrated that high consumption of fresh fruits, vegetables, high level of selenium and zinc in drinking water, sufficient iron, and cholesterol protect against GC, while; smoked , pickled, and preserved foods in salt, and nitrites increase the risk of GC. Epidemiological studies have also proved that H. pylori infection and a high salt diet could independently induce atrophic gastritis and intestinal metaplasia. Recently, studies have been demonstrated that dietary factors directly influence H. pylori virulence. The use of appropriate diet could reduce levels of H. pylori colonization or virulence and prevent or delay development of peptic ulcers or gastric carcinoma. This is attractive from a number of perspectives including those of cost, treatment tolerability, and cultural acceptability. This review will describe new insights into the pathogenesis of H. pylori in relation to environmental factors, especially dietary, not only to find the developed means for preventing and treating GC, but also for understanding the role of chronic inflammation in the development of other malignancies.
88Innate Immunity in Helicobacter pylori Infection and Gastric Oncogenesis.PubMed
Yuheng Zhang, Zhiyu Yan, Yuhao Jiao, et al.
Helicobacter. 2025 Mar-Apr;30(2):e70015. doi: 10.1111/hel.70015.
Helicobacter pylori is an extremely common cause of gastritis that can lead to gastric adenocarcinoma over time. Approximately half of the world's population is infected with H. pylori, making gastric cancer the fourth leading cause of cancer-related deaths worldwide. Innate immunity significantly contributes to systemic and local immune responses, maintains homeostasis, and serves as the vital link to adaptive immunity, and in doing so, mediates H. pylori infection outcomes and consequent cancer risk and development. The gastric innate immune system, composed of gastric epithelial and myeloid cells, is uniquely challenged by its need to interact simultaneously and precisely with commensal microbiota, exogenous pathogens, ingested substances, and endogenous exfoliated cells. Additionally, innate immunity can be detrimental by promoting chronic infection and fibrosis, creating an environment conducive to tumor development. This review summarizes and discusses the complex role of innate immunity in H. pylori infection and subsequent gastric oncogenesis, and in doing so, provides insights into how these pathways can be exploited to improve prevention and treatment.
89p27kip1 deficiency confers susceptibility to gastric carcinogenesis in Helicobacter pylori-infected mice.PubMed
Noriyoshi Kuzushita, Arlin B Rogers, Nola A Monti, et al.
Gastroenterology. 2005 Nov;129(5):1544-56. doi: 10.1053/j.gastro.2005.07.056.
BACKGROUND & AIMS: Determining how Helicobacter pylori promotes gastric cancer and whether H pylori eradication decreases cancer risk would be helped by suitable murine models. Mice lacking the cyclin-dependent kinase inhibitor p27kip1 are susceptible to carcinogen-induced tumors. Furthermore, p27 stimulates gastric epithelial apoptosis and inhibits proliferation, expression is decreased by H pylori, and low levels are associated with a poor prognosis in gastric cancer. We therefore evaluated p27-deficient mice as a model for H pylori-associated gastric cancer. METHODS: Wild-type and p27-/- C57BL/6 mice were infected with H pylori mouse-adapted Sydney strain at 6-8 weeks of age and 6-10 mice of each type were euthanized 15, 30, 45, 60, and 75 weeks later. RESULTS: Uninfected p27-/- mice developed gastric hyperplasia. H pylori-infected p27-/- mice frequently developed intestinal metaplasia (40% at 30 weeks, 67% at 45 weeks), and after 60 weeks 7 of 12 mice developed significant dysplasia and gastric cancer, recapitulating human intestinal-type gastric carcinogenesis. Wild-type mice developed intestinal metaplasia only after 75 weeks of infection; significant gastric dysplasia was observed in 1 animal (P < .05 for each comparison with p27-/- mice). No disease developed in uninfected mice. H pylori infection in p27-/- mice was associated with significantly decreased apoptosis and increased epithelial proliferation, inflammation, and H pylori density compared with infection in wild-type mice. CONCLUSIONS: p27 loss and H pylori colonization cooperate to produce gastric cancer. The p27-deficient mouse affords opportunities to examine the pathogenesis of H pylori in gastric carcinogenesis and to test eradication and chemopreventive strategies.
90Analysis of the correlation between P27 expression and Helicobacter pylori infection in gastric cancer.PubMed
Lin Li, Wei Wu, Wanchao Zheng, et al.
APMIS. 2022 Jan;130(1):21-25. doi: 10.1111/apm.13193. Epub 2021 Nov 23.
We aimed to explore the correlation between P27 expression and Helicobacter pylori (H. pylori) infection in gastric cancer, so as to provide evidence for understanding the pathogenesis of gastric cancer caused by H. pylori infection. A total of 82 samples of gastric cancer tissues and 56 samples of tumor-adjacent normal tissues collected from the gastrectomy were enrolled in this study. Then, 14C-urease breathing test was carried out to evaluate the infection of H. pylori in gastric cancer tissues, the expression of P27 in the tissue samples was detected by the immunohistochemistry staining, and the correlation between the H. pylori infection and P27 expression in gastric cancer was analyzed. Of 82 gastric cancer patients, there were 53 patients with H. pylori infection (64.63%). Among the patients with highly or moderately differentiated gastric cancer, the expression of P27 was much higher than that of patients with poorly differentiated gastric cancer (p < 0.01). Besides, comparison of the P27 expression between males and females, among different age groups, tumor sizes, TNM stages, tumor infiltration degrees, or lymph node metastasis, showed no significant differences (p > 0.05). Analysis of the correlation revealed that P27 expression was negatively correlated with the infection of H. pylori (p < 0.01). Multifactorial logistics regression analysis indicated that tumor differentiation was a risk factor of P27-positive expression in gastric cancer tissues (p < 0.01). In addition, P27 expression in the gastric cancer tissues was lower than that in the tumor-adjacent normal tissues (p < 0.01). In gastric cancer patients, expression of P27 is correlated with H. pylori infection which, via downregulating P27, can cause the cancerization of gastric mucosa, and P27, for its role in the development and progression of gastric cancer, is a potential auxiliary indicator for clinical diagnosis whether gastric cancer is complicated with H. pylori infection. So, P27 is a key indicator for diagnosis, treatment, and prognostic evaluation of disease in the advanced stage.
91Innate immune activation and modulatory factors of Helicobacter pylori towards phagocytic and nonphagocytic cells.PubMed
Larissa Faass, Martina Hauke, Saskia C Stein, et al.
Curr Opin Immunol. 2023 Jun;82:102301. doi: 10.1016/j.coi.2023.102301. Epub 2023 Mar 16.
Helicobacter pylori is an intriguing obligate host-associated human pathogen with a specific host interaction biology, which has been shaped by thousands of years of host-pathogen coevolution. Molecular mechanisms of interaction of H. pylori with the local immune cells in the human system are less well defined than epithelial cell interactions, although various myeloid cells, including neutrophils and other phagocytes, are locally present or attracted to the sites of infection and interact with H. pylori. We have recently addressed the question of novel bacterial innate immune stimuli, including bacterial cell envelope metabolites, that can activate and modulate cell responses via the H. pylori Cag type IV secretion system. This review article gives an overview of what is currently known about the interaction modes and mechanisms of H. pylori with diverse human cell types, with a focus on bacterial metabolites and cells of the myeloid lineage including phagocytic and antigen-presenting cells.
92Metagenomic and single-cell RNA-Seq survey of the Helicobacter pylori-infected stomach in asymptomatic individuals.PubMed
Chiara Sorini, Kumar P Tripathi, Shengru Wu, et al.
JCI Insight. 2023 Feb 22;8(4):e161042. doi: 10.1172/jci.insight.161042.
Helicobacter pylori colonization of the gastric niche can persist for years in asymptomatic individuals. To deeply characterize the host-microbiota environment in H. pylori-infected (HPI) stomachs, we collected human gastric tissues and performed metagenomic sequencing, single-cell RNA-Seq (scRNA-Seq), flow cytometry, and fluorescent microscopy. HPI asymptomatic individuals had dramatic changes in the composition of gastric microbiome and immune cells compared with noninfected individuals. Metagenomic analysis uncovered pathway alterations related to metabolism and immune response. scRNA-Seq and flow cytometry data revealed that, in contrast to murine stomachs, ILC2s are virtually absent in the human gastric mucosa, whereas ILC3s are the dominant population. Specifically, proportion of NKp44+ ILC3s out of total ILCs were highly increased in the gastric mucosa of asymptomatic HPI individuals, and correlated with the abundance of selected microbial taxa. In addition, CD11c+ myeloid cells and activated CD4+ T cells and B cells were expanded in HPI individuals. B cells of HPI individuals acquired an activated phenotype and progressed into a highly proliferating germinal-center stage and plasmablast maturation, which correlated with the presence of tertiary lymphoid structures within the gastric lamina propria. Our study provides a comprehensive atlas of the gastric mucosa-associated microbiome and immune cell landscape when comparing asymptomatic HPI and uninfected individuals.
93Epidemiology, Diagnosis and Risk Factors of Helicobacter pylori Infection.PubMed
Kallirroi Kotilea, Patrick Bontems, Eliette Touati
Adv Exp Med Biol. 2019;1149:17-33. doi: 10.1007/5584_2019_357.
Helicobacter pylori is a human-specific pathogen, which leads to gastric pathologies including gastric cancer. It is a highly unique bacterium considered as a carcinogenic agent. H. pylori remains a major human health problem, responsible for ~90% of the gastric cancer cases. Approximately four billion individuals have been detected for H. pylori infection worldwide in 2015. At the turn of the twenty-first century, the prevalence of H. pylori has been declining in highly industrialized countries of the Western world, whereas prevalence has plateaued at a high level in developing and newly industrialized countries. However, the infection status remains high in immigrants coming from countries with high prevalence of H. pylori infection. H. pylori can be diagnosed both by invasive and non-invasive methods. Urea breath test and stool antigens detection are among the most commonly used non-invasive ones. Although the way H. pylori is transmitted remains still not fully clear, the level of contamination is strongly dependent on the familial and environmental context, with a drastic impact of living conditions with poor hygiene and sanitation. However, familial socioeconomic status is the main risk factor for H. pylori infection among children. In addition, food and water source have a high impact on the prevalence of H. pylori infection worldwide. This chapter highlights the latest knowledge in the epidemiology of H. pylori infection, its diagnosis and critical risk factors responsible for its high prevalence in some populations and geographic areas.
94Helicobacter pylori: epidemiology and routes of transmission.PubMed
L M Brown
Epidemiol Rev. 2000;22(2):283-97. doi: 10.1093/oxfordjournals.epirev.a018040.
H. pylori is a common bacterium, and approximately 50 percent of the world's population has been estimated to be infected (198). Humans are the principal reservoir. The prevalence of H. pylori infection varies widely by geographic area, age, race, ethnicity, and SES. Rates appear to be higher in developing than in developed countries, with most of the infections occurring during childhood, and they seem to be decreasing with improvements in hygiene practices. H. pylori causes chronic gastritis and has been associated with several serious diseases of the gastrointestinal tract, including duodenal ulcer and gastric cancer. Since its "discovery" in 1982 by Warren and Marshall (1), H. pylori has been the topic of extensive research. A number of studies have used questionnaire components to investigate factors possibly related to the etiology of H. pylori infection. The majority of recent studies have not found tobacco use or alcohol consumption to be risk factors for H. pylori infection. Adequate nutritional status, especially frequent consumption of fruits and vegetables and of vitamin C, appears to protect against infection with H. pylori. In contrast, food prepared under less than ideal conditions or exposed to contaminated water or soil may increase the risk. Overall, inadequate sanitation practices, low social class, and crowded or high-density living conditions seem to be related to a higher prevalence of H. pylori infection. This finding suggests that poor hygiene and crowded conditions may facilitate transmission of infection among family members and is consistent with data on intrafamilial and institutional clustering of H. pylori infection. Understanding the route of H. pylori transmission is important if public health measures to prevent its spread are to be implemented. Iatrogenic transmission of H. pylori following endoscopy is the only proven mode. For the general population, the most likely mode of transmission is from person to person, by either the oral-oral route (through vomitus or possibly saliva) or perhaps the fecal-oral route. The person-to-person mode of transmission is supported by the higher incidence of infection among institutionalized children and adults and the clustering of H. pylori infection within families. Also lending support to this concept is the detection of H. pylori DNA in vomitus, saliva, dental plaque, gastric juice, and feces. Waterborne transmission, probably due to fecal contamination, may be an important source of infection, especially in parts of the world in which untreated water is common. Recent studies in the United States have linked clinical H. pylori infection with consumption of H. pylori-contaminated well water. This area of research is worthy of further investigation. Although H. pylori has been isolated in domestic cats, additional research has suggested that H. pylori is probably uncommon in domestic cats and thus is probably not a major concern for cat owners. Several studies have suggested sheep as a possible source of H. pylori transmission, a hypothesis that deserves additional investigation. The most recent reservoir suggested for H. pylori transmission is the housefly. However, evidence is lacking that H. pylori can be transmitted to humans from flies that have been in contact with H. pylori-infected feces. Nevertheless, the hypothesis is appealing since flies are known to carry many other infectious diseases. Knowledge of the epidemiology and mode of transmission of H. pylori is important to prevent its spread and may be useful in identifying high-risk populations, especially in areas that have high rates of gastric lymphoma, gastric cancer, and gastric ulcer.
95Methods for detection of Helicobacter pylori from stool sample: current options and developments.PubMed
Enming Qiu, Zhou Li, Shuai Han
Braz J Microbiol. 2021 Dec;52(4):2057-2062. doi: 10.1007/s42770-021-00589-x. Epub 2021 Aug 15.
Accurate detection of Helicobacter pylori infection and determination of antibiotics have significant meaning in clinical practice. The detection methods can be categorized into two types, invasive and non-invasive, but nowadays we use the urease breath test most frequently which is non-invasive. However, many developing countries cannot meet the requirements for having specialized equipment and they lack trained personnel. Also, for the children, it is difficult to make them cooperate for the test. Methods that detect Helicobacter pylori from stool sample can be a promising alternative for detection used in children and mass screening. Stool antigen tests have several advantages such as rapidity, simplicity, and cheapness, though their results may be influenced by the heterogenicity of antigens, the nature of biochemical techniques, and the amount of antigen presented in the stool. PCR-based methods can specifically detect Helicobacter pylori infection and antibiotic resistance by targeting specific gene sequence, but they also are limited by the requirements of facilities and experts, the existence of inhibitory substance, and interference from the dead bacteria. Some novel methods also deserve our attention. Here we summarized the results of researches about methods using stool sample and we hope our work can help clinicians choose the appropriate test in clinical practice.
96Diagnosis of Helicobacter pylori infection: Current options and developments.PubMed
Yao-Kuang Wang, Fu-Chen Kuo, Chung-Jung Liu, et al.
World J Gastroenterol. 2015 Oct 28;21(40):11221-35. doi: 10.3748/wjg.v21.i40.11221.
Accurate diagnosis of Helicobacter pylori (H. pylori) infection is a crucial part in the effective management of many gastroduodenal diseases. Several invasive and non-invasive diagnostic tests are available for the detection of H. pylori and each test has its usefulness and limitations in different clinical situations. Although none can be considered as a single gold standard in clinical practice, several techniques have been developed to give the more reliable results. Invasive tests are performed via endoscopic biopsy specimens and these tests include histology, culture, rapid urease test as well as molecular methods. Developments of endoscopic equipment also contribute to the real-time diagnosis of H. pylori during endoscopy. Urea breathing test and stool antigen test are most widely used non-invasive tests, whereas serology is useful in screening and epidemiological studies. Molecular methods have been used in variable specimens other than gastric mucosa. More than detection of H. pylori infection, several tests are introduced into the evaluation of virulence factors and antibiotic sensitivity of H. pylori, as well as screening precancerous lesions and gastric cancer. The aim of this article is to review the current options and novel developments of diagnostic tests and their applications in different clinical conditions or for specific purposes.
97Diagnosis of Helicobacter pylori infection.PubMed
Emilie Bessède, Vitor Arantes, Francis Mégraud, et al.
Helicobacter. 2017 Sep;22 Suppl 1. doi: 10.1111/hel.12404.
Important progress is being made in endoscopic methods which allow clinicians to predict the presence of Helicobacter pylori based on characteristics of gastric mucosa and to obtain targeted biopsies. There are also important developments in molecular methods with various techniques derived from standard PCR, applied both on gastric biopsies and stool specimens. Progress is being made in microfluidic systems to get a reliable diagnosis in a very short time. The interest of the C urea breath test has been confirmed as well as stool antigen tests. Attempts are being made to find biological markers of premalignant conditions by serology, other than pepsinogens.
98Helicobacter Pylori Infection: Diagnostic Strategies in Primary Diagnosis and After Therapy.PubMed
Nathan S S Atkinson, Barbara Braden
Dig Dis Sci. 2016 Jan;61(1):19-24. doi: 10.1007/s10620-015-3877-4. Epub 2015 Sep 21.
Accurate diagnosis of Helicobacter pylori infection pre- and post-treatment is mandatory in the current era of decreasing prevalence and increasing antibiotic resistance. The diagnostic performance of most tests is poorer in clinical situations with low bacterial density which is seen in conditions such as atrophic gastritis or intake of antisecretory and antibiotic medications. Noninvasive tests require less cost and resource but provide excellent accuracy; however, endoscopy with testing of gastric biopsy specimens is indicated where alarming symptoms are present or antibiotic susceptibility testing by culture is desired. Newer modalities such as polymerase chain reaction testing provide additional virulence and antibiotic sensitivity profiling. This article outlines new developments and the key parameters of each test, as careful selection of test modality within the clinical context is required for adequate management of infected symptomatic patients.
99Accuracy of stool antigen test for the diagnosis of Helicobacter pylori infection in children: a meta-analysis.PubMed
Xiaoying Zhou, Jing Su, Guangxu Xu, et al.
Clin Res Hepatol Gastroenterol. 2014 Oct;38(5):629-38. doi: 10.1016/j.clinre.2014.02.001. Epub 2014 Mar 11.
INTRODUCTION: Helicobacter pylori (H. pylori) is regarded as a major pathogen in gastrointestinal diseases and the infection rate is still at a high level in children. Therefore, the diagnosis is of great clinical importance. The objective was to perform a meta-analysis on H. pylori stool antigen test (SAT) for the diagnosis of the infection in children. METHODS: Published information on the sensitivity and specificity of stool antigen test in each study was collected to assess the accuracy of the test for the diagnosis of H. pylori infection. Forty-five eligible studies were selected for analysis. Data on the publication year, H. pylori prevalence, eradication rate and gold standard of each study were summarized. RESULT: Forty-five studies, including 5931 patients, evaluated the accurancy of H. pylori SAT. Pooled sensitivity, specificity, LR+ and LR- were: 92.1%, 94.1%, 17.01, 0.085, respectively. Subgroup analyses were conducted to evaluate the sensitivity and specificity of H. pylori SAT in different situations and found that sensitivity and specificity were significantly higher when monoclonal H. pylori SAT and two or more reference methods were used. CONCLUSIONS: Detection of H. pylori antigen in stools with ELISA monoclonal antibodies is a non-invasive efficient test for the diagnosis of infection in children. However, the available one-step and polyclonal SAT tests are still unreliable.
100Evaluation of two stool antigen tests for the detection of Helicobacter pylori infection in the Chinese population.PubMed
Benjamin Chun Yu Wong, Harry Hua Xiang Xia, Hess Kwan Lok Cheung, et al.
J Gastroenterol Hepatol. 2003 Jan;18(1):26-31. doi: 10.1046/j.1440-1746.2003.02926.x.
BACKGROUND AND AIM: The stool antigen test, the HpSA test, has been validated mainly in Western countries, but not properly in the Chinese population. Recently, another stool antigen test, the Apollo test, was developed, but its accuracy has rarely been validated. The aim of this study is to compare the accuracy of these two tests in the diagnosis of Helicobacter pylori infection in the Chinese population. METHODS: Consecutive dyspeptic patients referred for upper endoscopy were recruited. During endoscopy, biopsies were taken for the rapid urease test and histological examination as the gold standard. Stool specimens were collected and used for the HpSA and Apollo tests. RESULTS: Overall, 86 patients (39 males and 47 females, with a mean age of 55.8 years) were recruited. Helicobacter pylori infection was present in 44 (51%) patients as determined by the gold standard. The sensitivity, specificity and accuracy were 86.4, 100, and 93.0%, respectively, for the HpSA, and 90.9, 97.6, and 94.2%, respectively, for the Apollo test when cases with equivocal results were considered as positive. In addition, agreement was achieved in 81 (94.2%) cases between the two tests, with a Kappa value of 0.887. CONCLUSION: Both the HpSA and Apollo tests achieve acceptable sensitivity and excellent specificity, with accuracies of over 90% for the detection of H. pylori infection in the Chinese population.
101Comparative study of serology and histology based detection of Helicobacter pylori infections: a large population-based study of 7,241 subjects from China.PubMed
Y H Gong, L P Sun, S G Jin, et al.
Eur J Clin Microbiol Infect Dis. 2010 Jul;29(7):907-11. doi: 10.1007/s10096-010-0944-9. Epub 2010 May 5.
Two detection methods for H. pylori infections, i.e. serological antibody titer measurements by Hp-ELISA and histological scoring by HE staining, have been compared to investigate the relationship between the diagnosis methods, to clarify the application scope of each diagnosis method and to determine its influencing factors. In the 7,241 subjects who participated in gastric cancer screening, H. pylori infection rate was 70.14% by the Hp-HE method and 41.87% by the Hp-ELISA method when 34EIU was recognized as the cut-off value. The IgG titers increased with the elevation of HE scores; however, the two methods were not closely correlated among those in different gastric disease status. Age, gender and drinking status did not have significant impact on the relationship between the two methods; however, smoking status seemed to significantly influence the correlation of the two diagnosis methods. In conclusion, it was necessary to reevaluate the cut-off value when using ELISA test kits in different population groups. In most cases, the results of two H. pylori infection diagnosis methods show high correlation. However, this relationship can be affected by smoking and gastric diseases status. Additionally, the dynamic change of H. pylori antibody titers is an indicator of gastric disease development.
102Detection of Helicobacter pylori Infection and Antibiotic Resistance via Stool Quantitative Polymerase Chain Reaction Analysis.PubMed
Jin-Xin Lai, Hui-Min Chen, Cheng-Yuan He, et al.
J Vis Exp. 2025 May 16(219). doi: 10.3791/67710.
Helicobacter pylori (H. pylori) is widely prevalent worldwide, with approximately 50% of the global population having a history of H. pylori infection. In China, the infection rate ranges from 40% to 70%. H. pylori is primarily associated with gastrointestinal diseases such as chronic gastritis, gastric ulcers, and duodenal ulcers. Currently, the clinical treatment for H. pylori infection involves either triple or quadruple therapy. However, the extensive use of antibiotics has led to the development of antibiotic resistance in H. pylori. Therefore, detecting both H. pylori and its antibiotic resistance is crucial for guiding clinical treatment. Diagnostic methods for H. pylori include urea breath test (UBT), antigen test, serological antibody test, endoscopy, rapid urease test (RUT), and bacterial culture. While the first three methods are non-invasive, they do not allow for bacterial recovery and, thus, cannot be used for resistance testing. The latter three methods are invasive, expensive, require high technical expertise, and may cause harm to patients. Therefore, a non-invasive, rapid method for simultaneous detection of H. pylori infection and antibiotic resistance is of utmost clinical importance for the effective eradication of H. pylori. This paper aims to introduce a specific protocol that combines quantitative polymerase chain reaction (qPCR) with TaqMan fluorescent probe technology to rapidly detect H. pylori infection and antibiotic resistance. This method provides a convenient, rapid, and non-invasive way to diagnose H. pylori infection and resistance, unlike traditional bacterial culture and other techniques. qPCR is used to identify the infection and detect mutations in the 23S rRNA and gyrA genes, which are linked to resistance to clarithromycin and quinolones, respectively. Compared to conventional culture techniques, this approach offers a non-invasive, cost-effective, and time-efficient method for detecting Helicobacter pylori infection and determining its antibiotic resistance.
103Endoscopic diagnosis of H. pylori infection.PubMed
Rodrigo Garcés-Durán, Joan Llach, Angella Da Fieno, et al.
Gastroenterol Hepatol. 2023 Jun-Jul;46(6):483-488. doi: 10.1016/j.gastrohep.2022.09.008. Epub 2022 Oct 3.
Helicobacter pylori (H. pylori) infection is highly prevalent in our environment and is associated with highly relevant gastric disease, both benign and malignant. The gold standard for diagnosis is histological confirmation by biopsy. However, there is increasing evidence that optical endoscopic diagnosis could have a fundamental role in avoiding unnecessary biopsies in certain cases. Specifically, the regular distribution of the collecting venules (RAC pattern) seems to have a high negative predictive value (NPV) to rule out infection. This review describes the most outstanding endoscopic findings with the best diagnostic potential for H. pylori infection after an exhaustive search comparing the most relevant studies that have been carried out in Europe and the East.
104Helicobacter pylori: management in 2013.PubMed
Yesim Ozen Alahdab, Cem Kalayci
World J Gastroenterol. 2014 May 14;20(18):5302-7. doi: 10.3748/wjg.v20.i18.5302.
Helicobacter pylori (H. pylori) is a prevalent, worldwide, chronic infection. Choice of treatment can be modified according to antibiotic-resistance rates of H. pylori. The ideal therapeutic regimen for H. pylori infection should achieve an eradication rate of ≥ 80%. In some countries, triple therapy with a proton-pump inhibitor (PPI), clarithromycin, and amoxicillin or metronidazole is still the best option. Bismuth-containing quadruple therapy consisting of bismuth salts, tetracycline, metronidazole and PPI, may be the preferred option in countries with clarithromycin resistance > 20%. Sequential therapy including a PPI and amoxicillin given for the first 5 d, followed by triple therapy including a PPI, clarithromycin, and nitroimidazole antimicrobial (all twice daily) for the remaining 5 d, can be another option for the first-line treatment of H. pylori. Recent data suggest that treatment with PPI, levofloxacin, and amoxicillin for 10 d is a good choice for second-line therapy. Concomitant therapy consisting of PPI, amoxicillin, clarithromycin and metronidazole is another option for second-line treatment. If second-line treatment also fails, it is recommended to culture H. pylori from biopsy specimens and perform antimicrobial susceptibility testing. Rescue treatment should be based on antimicrobial susceptibility.
1052022 Chinese national clinical practice guideline on Helicobacter pylori eradication treatment.PubMed
Liya Zhou, Hong Lu, Zhiqiang Song, et al.
Chin Med J (Engl). 2022 Dec 20;135(24):2899-2910. doi: 10.1097/CM9.0000000000002546.
BACKGROUND: Helicobacter pylori ( H. pylori ) infection is an infectious disease with a prevalence rate of up to 50% worldwide. It can cause indigestion, gastritis, peptic ulcer, and gastric cancer. H. pylori eradication treatment can effectively control disease progression and reduce the risk of the above conditions. However, the escalating trend of antibiotic resistance presents a global challenge for H. pylori eradication. We aim to provide guidance on pharmacological treatment of H. pylori infection. METHODS: This clinical practice guideline is developed following the World Health Organization's recommended process, adopting Grading of Recommendations Assessment, Development and Evaluation in assessing evidence quality, and utilizing Evidence to Decision framework to formulate clinical recommendations, minimizing bias and increasing transparency of the clinical practice guideline development process. We used the Reporting Items for practice Guidelines in HealThcare (RIGHT) statement and The Appraisal of Guidelines for Research and Evaluation II (AGREE II) as reporting and conduct guides to ensure the guideline's completeness and transparency. RESULTS: Though decreasing in developed countries, the prevalence of H. pylori remains high in developing countries, causing a major public health burden. This clinical practice guideline contains 12 recommendations concerning pharmacological treatment for H. pylori eradication. Among them, it is worth highlighting that bismuth preparations are inexpensive, safe, and effective, consequently making bismuth quadruple therapy a preferred choice for initial and rescue treatment. In empirical treatment, high-dose dual therapy is equally effective compared with bismuth quadruple therapy. CONCLUSIONS: The 12 recommendations in this clinical practice guideline are formed with consideration for stakeholders' values and preferences, resource use, feasibility, and acceptability. Recommendations are generalizable to resource limited settings with similar antibiotic resistance pattern as China, and lower middle-income countries facing comparable sociological and technical challenges. REGISTRATION: Guidelines International Network (GIN) website, https://guidelines.ebmportal.com/node/69996 .
106The status and progress of first-line treatment against infection: a review.PubMed
Caiqi Liu, Yuan Wang, Jiaqi Shi, et al.
Therap Adv Gastroenterol. 2021 Jun 28;14:1756284821989177. doi: 10.1177/1756284821989177. eCollection 2021.
(HP) is a major causative agent of chronic gastritis and peptic ulcer. HP is also engaged in the development of gastric cancer and gastric mucosa-associated lymphoid tissue lymphoma. It is an important pathogenic factor in various other systemic diseases, such as vitamin B12 deficiency, iron deficiency, and idiopathic thrombocytopenia. The current consensus is that unless there is a special reason, eradication therapy should be implemented whenever HP infection is found, and it is ideally successful the first time. International guidelines recommend that under certain conditions, treatment should be personalized based on drug susceptibility testing. However, drug susceptibility testing is often not available because it is expensive, time-consuming, and difficult to obtain living tissue. Each region has separately formulated guidelines or consensuses on empirical therapy. Owing to an increasing drug resistance rate in various places, the eradication rate of proton pump inhibitor (PPI) triple therapy and sequential therapy has been affected. These regimens are rarely used; the PPI triple especially has been abandoned in most areas. Currently, radical treatment regimens for HP involve bismuth-containing quadruple therapy and concomitant therapy. However, quadruple therapy has its own limitations, such as complex drug administration. To improve the effectiveness, safety, and compliance, many clinical studies have proposed useful modified regimens, which mainly include the modified bismuth-containing quadruple regimen, high-dose dual therapy, and vonoprazan-containing regimens. Studies have shown that these emerging regimens have acceptable eradication rates and safety, and are expected to become first-line treatments in empirical therapy. However, the problem of decline in the eradication rate caused by drug resistance has not been fundamentally solved. This review not only summarizes the effectiveness of mainstream regimens in the first-line treatment of HP infection with the currently increasing antibiotic resistance rates, but also summarizes the effectiveness and safety of various emerging treatment regimens.
107Ten-Day Vonoprazan-Amoxicillin Dual Therapy as a First-Line Treatment of Helicobacter pylori Infection Compared With Bismuth-Containing Quadruple Therapy.PubMed
Hai-Sheng Qian, Wen-Jie Li, Yi-Ni Dang, et al.
Am J Gastroenterol. 2023 Apr 1;118(4):627-634. doi: 10.14309/ajg.0000000000002086. Epub 2022 Dec 2.
INTRODUCTION: No study has investigated the efficacy and safety of vonoprazan-amoxicillin dual therapy compared with bismuth quadruple therapy (B-quadruple). This study aimed to evaluate the efficacy and safety of 10-day vonoprazan-amoxicillin dual therapy as a first-line treatment of Helicobacter pylori infection compared with B-quadruple and to explore the optimal dosage of amoxicillin in the dual therapy. METHODS: A total of 375 treatment-naive, H. pylori -infected subjects were randomly assigned in a 1:1:1 ratio into 3 regimen groups including VHA-dual (vonoprazan 20 mg twice/day + amoxicillin 750 mg 4 times/day), VA-dual (vonoprazan 20 mg + amoxicillin 1,000 mg twice/day), and B-quadruple (esomeprazole 20 mg + bismuth 200 mg + amoxicillin 1,000 mg + clarithromycin 500 mg twice/day). Eradication rates, adverse events (AEs), and compliance were compared between 3 groups. RESULTS: The eradication rates of B-quadruple, VHA-dual, and VA-dual were 90.9%, 93.4%, and 85.1%, respectively, by per-protocol analysis; 89.4%, 92.7%, and 84.4%, respectively, by modified intention-to-treat analysis; 88.0%, 91.2%, and 82.4%, respectively, by intention-to-treat analysis. The efficacy of the VHA-dual group was not inferior to the B-quadruple group ( P < 0.001), but VA-dual did not reach a noninferiority margin of -10%. The AEs rates of the B-quadruple group were significantly higher than those of the VHA-dual ( P = 0.012) and VA-dual ( P = 0.001) groups. There was no significant difference in medication compliance among 3 treatment groups ( P = 0.995). CONCLUSIONS: The 10-day VHA-dual therapy provided satisfactory eradication rates of >90%, lower AEs rates, and similar adherence compared with B-quadruple therapy as a first-line therapy for H. pylori infection. However, the efficacy of VA-dual therapy was not acceptable.
108Dual therapy for Helicobacter pylori infection.PubMed
Miao Duan, Jing Liu, Xiuli Zuo
Chin Med J (Engl). 2023 Jan 5;136(1):13-23. doi: 10.1097/CM9.0000000000002565.
Bismuth-containing quadruple therapy (BQT) has long been recommended for Helicobacter pylori ( H. pylori ) eradication in China. Meanwhile, in the latest national consensus in China, dual therapy (DT) comprising an acid suppressor and amoxicillin has also been recommended. In recent years, the eradication rate of H. pylori has reached >90% using DT, which has been used not only as a first-line treatment but also as a rescue treatment. Compared with BQT, DT has great potential for H. pylori eradication; however, it has some limitations. This review summarizes the development of DT and its application in H. pylori eradication. The H. pylori eradication rates of DT were comparable to or even higher than those of BQT or standard triple therapy, especially in the first-line treatment. The incidence of adverse events associated with DT was lower than that with other therapies. Furthermore, there were no significant differences in the effects of dual and quadruple therapies on gastrointestinal microecology. In the short term, H. pylori eradication causes certain fluctuations in the gastrointestinal microbiota; however, in the long term, the gastrointestinal microbiota eventually returns to its normal state. In the penicillin-naïve population, patients receiving DT have a high eradiation rate, better compliance, lower incidence of adverse reactions, and lower primary and secondary resistance to amoxicillin. These findings suggest the safety, efficacy, and potential of DT for H. pylori eradication.
109Optimal Duration of Bismuth-Containing Quadruple Therapy for Helicobacter pylori Eradication: A Systematic Review and Meta-Analysis.PubMed
Miao Duan, Qingzhou Kong, Hui Wang, et al.
Helicobacter. 2024 Sep-Oct;29(5):e13144. doi: 10.1111/hel.13144.
BACKGROUND: The eradication of Helicobacter pylori (H. pylori) is crucial due to its rising prevalence and increasing resistance. Bismuth-containing quadruple therapies (BcQTs) have been proposed as a viable treatment option; however, the optimal duration for it remains contentious. This systematic review and meta-analysis aimed to compare the clinical efficacy of short-term BcQT (defined as 7 or 10 days) with a standard 14-day course. METHODS: A systematic search of PubMed, Embase, Web of Science, and the Cochrane Library was conducted for randomized controlled trials published in English until June 20, 2024. Eligibility criteria were applied to identify relevant studies. Summary risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for the included studies regarding eradication rates, adverse effects, and compliance. This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and was previously registered in PROSPERO under registration number CRD42024547773. RESULTS: This meta-analysis finally included 15 trials involving a total of 4505 patients. The eradication rates for short courses of BcQT were lower than those for the 14-day course (RR 0.96, 95% CI 0.93-0.99). However, the eradication rate for the 10-day therapy was comparable to that of the 14-day therapy (RR 0.98, 95% CI 0.95-1.00). Subgroup analyses of antibiotic combinations indicated that tetracycline and metronidazole combinations yielded similar H. pylori eradication rates in the 7-day versus the 14-day BcQT (RR 0.93, 95% CI 0.84-1.02). In the potassium-competitive acid blocker subgroup, the eradication rates remained similar across the 14-day group and the short-course treatment groups, whether evaluating the short-term treatment groups as a whole or the 7- and 10-day subgroups separately. Additionally, the adverse effects and compliance associated with the short course of BcQT were comparable to those of the 14-day therapy. CONCLUSION: A 10-day course of BcQT may represent the optimal treatment duration. Nevertheless, the choice of antibiotic combination should be guided by the regional antibiotic resistance patterns of H. pylori, as combinations with lower resistance rates are more effective. TRIAL REGISTRATION: PROSPERO number: CRD42024547773.
110Bismuth-Containing Quadruple Therapy for Helicobacter pylori Eradication: A Randomized Clinical Trial of 10 and 14 Days.PubMed
Yu-Ming Ding, Miao Duan, Zhong-Xue Han, et al.
Dig Dis Sci. 2024 Jul;69(7):2540-2547. doi: 10.1007/s10620-024-08460-3. Epub 2024 May 3.
BACKGROUND: Bismuth-containing quadruple therapy is the first-line treatment for eradicating Helicobacter pylori (H. pylori). The optimal duration for H. pylori eradication using bismuth-containing quadruple therapy remains controversial. Therefore, we aimed to compare the clinical effects of the 10- and 14-day bismuth-containing quadruple treatment regimen to eradicate H. pylori. METHODS: Treatment-naïve patients with H. pylori infection (n = 1300) were enrolled in this multicenter randomized controlled study across five hospitals in China. They were randomized into 10- or 14-day treatment groups to receive bismuth-containing quadruple therapy as follows: vonoprazan 20 mg twice daily; bismuth 220 mg twice daily; amoxicillin 1000 mg twice daily; and either clarithromycin 500 mg twice daily or tetracycline 500 mg four times daily. At least 6 weeks after treatment, we performed a C-urea breath test to evaluate H. pylori eradication. RESULTS: The per-protocol eradication rates were 93.22% (564/605) and 93.74% (569/607) (p < 0.001) and the intention-to-treat eradication rates were 88.62% (576/650) and 89.38% (581/650) (p = 0.007) for the 10- and 14-day regimens, respectively. Incidence of adverse effects was lower in patients who received 10- vs. 14 days of treatment (22.59% vs. 28.50%, p = 0.016). We observed no significant differences in the compliance to treatment or the discontinuation of therapy because of severe adverse effects between the groups. CONCLUSION: Compared with the 14-day bismuth-containing quadruple regimens, the 10-day regimen demonstrated a non-inferior efficacy and lower incidence of adverse effects. Therefore, the 10-day regimen is safe and tolerated and could be recommended for H. pylori eradication (NCT05049902).
111Amoxicillin high-dose dual therapy for primary eradication: Proton pump inhibitor and potassium-competitive acid blocker, which's better?PubMed
Xue-Er Yang, Sheng-Jun Zhang, Yuan Liu, et al.
World J Gastroenterol. 2025 Apr 7;31(13):100863. doi: 10.3748/wjg.v31.i13.100863.
BACKGROUND: Effective acid suppression significantly enhances the eradication rate of (). AIM: To assess the efficacy and safety of high-dose dual therapy (HDDT) utilizing various highly potent antisecretory medications, thereby providing additional clinical guidance for eradication. METHODS: The study population comprised untreated patients from three medical centers in central China. From February 10, 2024 to March 31, 2024, 439 subjects were randomly allocated to either the esomeprazole-amoxicillin (EA) or esomeprazole-amoxicillin-clarithromycin-bismuth (B-quadruple) group. Subsequently, from April 1, 2024 to May 10, 2024, 367 subjects were randomly assigned to either the vonoprazan-amoxicillin (VA) or vonoprazan-amoxicillin-clarithromycin (VAC) group. The study recorded treatment efficacy, adverse events, compliance, symptom alleviation, and associated costs. RESULTS: EA-dual demonstrated non-inferiority to B-quadruple regimen in modified intention-to-treat (mITT) and per-protocol (PP) analyses ( < 0.025). However, the eradication rate of EA was lower than that of the B-quadruple group [70.59% 83.49%, 92.86% 98.38%, 93.94% 98.38%, intention-to-treat (ITT), mITT, PP respectively, < 0.05]. In ITT, mITT, and PP analyses, VA-dual was non-inferior to VAC treatment (84.15% 83.15%, 96.25% 92.73%, 96.75% 93.75%, < 0.025). No significant differences were observed in adverse events, compliance, and symptom relief between groups. VA exhibited the lowest cost. Antibiotic use within 2 years, poor compliance, and suburban residence were associated with reduced eradication efficacy ( < 0.05). CONCLUSION: The HDDT based on vonoprazan demonstrated non-inferiority to the VAC triple regimen, suggesting its potential as a recommended first-line treatment for eradication. While B-quadruple therapy showed better eradication rate than EA therapy, the latter proved non-inferior in mITT and PP analyses. Notably, antibiotic use within the preceding two years, adherence to treatment protocols, and patient residence emerged as critical factors influencing eradication success.
112Efficacy and safety of vonoprazan and high-dose amoxicillin dual therapy in eradicating Helicobacter pylori: A systematic review and meta-analysis.PubMed
Ju Zhang, Huan Zhang, Xiao-Jing Zhu, et al.
Int J Antimicrob Agents. 2024 Nov;64(5):107331. doi: 10.1016/j.ijantimicag.2024.107331. Epub 2024 Sep 7.
BACKGROUND: Vonoprazan is a new acid-suppressing drug that provides an additional choice for eradicating Helicobacter pylori. The effectiveness and safety of vonoprazan and high-dose amoxicillin (VHA) dual therapy requires study in a systematic analysis. MATERIALS AND METHODS: A comprehensive search of the literature from the PubMed, Embase, Cochrane Library, and Web of Science databases was conducted up to 16 May 2024. Trials comparing H. pylori eradication rates, adverse events, and compliance of VHA dual therapy with that of other therapies were included. RevMan 5.4 was used for statistical analysis. RESULTS: Eleven randomised controlled trials (RCTs) and two retrospective clinical studies with 4570 samples were included. VHA dual therapy had superior H. pylori eradication rates (intention-to-treat [ITT]: 86.0% vs. 80.7%; odds ratio [OR]=1.36; 95% confidence interval [CI] 1.07-1.73; P=0.01; per-protocol [PP]: 90.6% vs. 85.7%; OR=1.42; 95% CI 1.07-1.88; P=0.02), fewer adverse events (15.4% vs. 27.7%; OR=0.49; 95% CI 0.35-0.68, P<0.0001), and similar compliance (94.6% vs. 93.2%; OR=1.27; 95% CI 0.98-1.64; P=0.07) compared with other guideline therapies. According to subgroup analysis with PP data, VHA dual therapy is more effective than bismuth quadruple therapy based on proton-pump inhibitors (P-BQT) (93.5% vs. 89.3%; OR=1.76; 95% CI 1.03-3.00; P=0.04). In addition, the eradication rates for 7-day, 10-day and 14-day VHA dual therapy were 65% (95% CI 0.55-0.75), 92% (95% CI 0.91-0.94) and 93% (95% CI 0.90-0.97), respectively. CONCLUSION: VHA dual therapy for 10 or 14 days showed superior efficacy and safety compared with therapies recommended by the guidelines and should be prioritised for adoption.
113Low-dose or high-dose amoxicillin in vonoprazan-based dual therapy for Helicobacter pylori eradication? A systematic review and meta-analysis.PubMed
Kun-Ping Ju, Qing-Zhou Kong, Yue-Yue Li, et al.
Helicobacter. 2024 Jan-Feb;29(1):e13054. doi: 10.1111/hel.13054.
BACKGROUND: The amoxicillin dose used in dual therapy to eradicate Helicobacter pylori varies across studies and the optimal amoxicillin dose for vonoprazan-based dual therapies remains unclear. We aimed to investigate the efficacy and safety of low- and high-dose amoxicillin in vonoprazan-amoxicillin dual therapy. MATERIALS AND METHODS: A comprehensive systematic review was conducted by searching databases from inception to October 2023. All trials that evaluated the effectiveness and safety of vonoprazan-amoxicillin dual therapy for eradicating H. pylori were included. Pooled eradication rate, incidence of adverse events, relative risks, and 95% confidence intervals are presented. RESULTS: Eighteen studies with 12 low-dose amoxicillin (VLA) and 13 high-dose amoxicillin (VHA) arms were included. The pooled eradication rates were 82.4% and 86.8% for VLA therapy, and 86.0% and 90.9% for VHA therapy by the intention-to-treat and per-protocol analyses, respectively. In the subgroup analysis stratified by duration, the eradication rates achieved in 7 days, 10 days, and 14 days treatments with VLA and VHA dual therapies were 80.8%, 84.2%, 83.1%, and 67.3%, 88.8%, 87.5%, respectively. In the four randomized controlled trials that directly compared VLA and VHA dual therapies, the efficacy was not statistically different in the intention-to-treat (76.9% vs 81.4%, p = 0.337) and per-protocol (81.6% vs 84.0%, p = 0.166) analyses. Additionally, the incidence of adverse events (p = 0.965) and compliance (p = 0.994) were similar in both groups. CONCLUSION: VLA therapy demonstrated comparable efficacy and safety to VHA therapy, along with regional differences. An appropriately extended treatment duration may be critical for therapeutic optimization of vonoprazan-amoxicillin treatment.
114Effects of amoxicillin dosage on cure rate, gut microbiota, and antibiotic resistome in vonoprazan and amoxicillin dual therapy for Helicobacter pylori: a multicentre, open-label, non-inferiority randomised controlled trial.PubMed
Yi Hu, Zhen-Yu Zhang, Fen Wang, et al.
Lancet Microbe. 2025 Mar;6(3):100975. doi: 10.1016/j.lanmic.2024.100975. Epub 2024 Dec 18.
BACKGROUND: Vonoprazan and amoxicillin (VA) dual therapy as a mainstream Helicobacter pylori regimen has gained momentum worldwide, but the optimum dosages remain unclear. We aimed to compare the efficacy and safety of VA dual therapy with 2 g amoxicillin or 3 g amoxicillin, and to assess the short-term effects of therapy on the gut microbiota and antibiotic resistome. METHODS: We conducted an open-label, non-inferiority randomised controlled trial at 12 centres in China. Individuals infected with H pylori, aged 18-70 years, and without previous eradication therapy were recruited. Participants were randomly assigned at a 1:1 ratio (block size of six) to receive vonoprazan (20 mg twice a day) with either low-dose amoxicillin (1 g twice a day; LVA therapy) or high-dose amoxicillin (1 g three times a day; HVA therapy) for 14 days. Gastric biopsies were collected before treatment for detection of antibiotic resistance. Stool samples were collected at baseline, week 2, and week 8-10 for shotgun metagenomic sequencing. The primary outcome was the eradication rate of H pylori, assessed by C urea breath test, in both intention-to-treat and per-protocol analyses. Secondary outcomes were adverse events, adherence, antibiotic resistance, and alterations to the gut microbiota and antibiotic resistome. The margin used to establish non-inferiority was -0·10. The trial was registered with ClinicalTrials.gov, NCT05649709. FINDINGS: Between Feb 13, 2023, and Jan 25, 2024, 504 patients (204 [40%] male and 300 [60%] female; mean age 43 years [SD 13]) were randomly assigned to LVA therapy or HVA therapy (n=252 in each group). No infections were resistant to amoxicillin. The H pylori eradication rate was 85·3% (215 of 252; 95% CI 80·4 to 89·2) in the LVA group and 86·5% (218 of 252; 81·7 to 90·2) in the HVA group in the intention-to-treat analysis (p=0·70) and 88·8% (213 of 240; 84·1 to 92·2) and 92·4% (218 of 236; 88·3 to 95·1), respectively, in the per-protocol analysis (p=0·18). The efficacy of LVA was non-inferior to HVA in the intention-to-treat analysis (risk difference -1·2%, 95% CI -7·3 to 4·9, p=0·0022) and the per-protocol analysis (-3·6%, -9·0 to 1·7, p=0·0085). 31 (12%) patients in the LVA group and 43 (17%) patients in the HVA group reported adverse events. Adherence to therapy was 97% in the LVA group and 96% in the HVA group. The diversity of gut microbiota decreased after treatment but was restored to baseline at week 8-10 in both groups. The abundance of beta-lactam-related resistance genes was increased at week 2 after treatment, and was restored to pretreatment level at week 8-10 for the LVA group but not the HVA group. INTERPRETATION: LVA dual therapy was effective and non-inferior to HVA dual therapy as first-line treatment of H pylori infection and showed a non-lasting effect on the abundance of beta-lactam-related resistance genes. High amoxicillin dosage (eg, 3 g per day) is not required to achieve high cure rates with vonoprazan dual therapy. FUNDING: National Natural Science Foundation of China, Project for Academic and Technical Leaders of Major Disciplines in Jiangxi Province, and Key Research and Development Program of Jiangxi Province.
115Efficacy and safety of high-dose ilaprazole-amoxicillin dual therapy for eradication: a prospective, single-center, randomized trial.PubMed
Jianping Cheng, Chanjuan Fan, Kun Huang, et al.
Front Pharmacol. 2023 Nov 7;14:1272744. doi: 10.3389/fphar.2023.1272744. eCollection 2023.
Until now, there have been no randomized controlled trials directly evaluating the efficacy of high-dose ilaprazole-amoxicillin dual therapy (HT) in comparison to other standard treatments for () infection. This study aimed to compare the effectiveness and safety of HT with bismuth quadruple therapy (BQT) as an initial treatment for . This single-center, prospective, randomized clinical controlled trial recruited 225 consecutive patients. They were assigned to either HT group (ilaprazole, 10 mg, twice daily; amoxicillin 1,000 mg, three times daily) or BQT group (compound bismuth aluminate granules, 2.6 g, three times daily; ilaprazole, 5 mg, twice daily; amoxicillin, 1,000 mg, twice daily; clarithromycin, 500 mg, twice daily) for 14 days. The C-urea breath test assessed eradication success 4 weeks after treatment. The primary outcome focused on the eradication rate, with secondary outcomes including safety and compliance. From February 2023 to March 2023, 228 subjects were screened, and 225 were randomized. The HT and BQT groups showed eradication rates of 76.3% and 61.3% ( = 0.015) both by intention-to-treat (ITT) analysis and per-protocol (PP) analysis. HT was associated with fewer adverse events than BQT (27.2% vs. 81.8%, = 0.002). The most commonly reported adverse events was bitter taste of mouth (3.5% vs. 60.4%, < 0.001). There was no significant difference in compliance between the two groups (89.5% vs. 92.8%, = 0.264). The 14-day HT treatment demonstrates better efficacy in eradication treatment and improved safety and compliance compared to BQT. The results provide supporting evidence for 14-day HT can be potentially considered as a first-line regimen for empirical treatment. https://www.chictr.org.cn/showproj.html?proj=186562, identifier ChiCTR2200066284.
116Antibiotic resistance in Helicobacter pylori: From potential biomolecular mechanisms to clinical practice.PubMed
Yifan Lin, Yongfu Shao, Jianing Yan, et al.
J Clin Lab Anal. 2023 Apr;37(7):e24885. doi: 10.1002/jcla.24885. Epub 2023 Apr 23.
Increasing rates of Helicobacter pylori resistance are associated with multiple clinical challenges. Bacterial factors linked to H. pylori resistance are mutations, efflux pumps, and biofilms. Gene mutations such as nucleic acid synthesis-related gene mutations, rRNA coding gene mutations, and cell wall synthesis-related gene mutations are the most important mechanisms by which H. pylori evades bactericidal effects. These mechanisms are also closely related to the biological activity of the efflux pump systems and biofilms. Activation of the efflux pump system and biofilm formation both lead to the emergence of MDR strains, further increasing the difficulty of eradication therapy. In this review, the status of antibiotic resistance in H. pylori from different regions and countries is summarized and compared, and H. pylori resistance profiles and their changing trends in the clinic are described. Then, research progress on biomolecular mechanisms underlying antibiotic resistance, diagnostic methods, and treatment strategies are introduced and discussed. Challenges resulting from increasing resistance, potential solutions to combat increasing resistance, and future directions are discussed to help clinicians and researchers better address the emergence and spread of resistant H. pylori strains and optimize drug regimens. With the rate of H. pylori resistance to commonly used antibiotics increasing, more attention should be given to the selection of antibiotics and to monitoring resistance when antibiotics are used for clinical eradication treatment. Individualized precise eradication treatment under the guidance of drug susceptibility testing will become the mainstream method of treatment in the future.
117Antimicrobial drug susceptibility testing for the management of infection in personalized eradication therapy.PubMed
Lingzhu Gou, Zenghui Ma, Mengyu Han, et al.
Front Microbiol. 2025 Aug 19;16:1626930. doi: 10.3389/fmicb.2025.1626930. eCollection 2025.
is a gram-negative bacterium that associated with diseases such as gastritis, peptic ulcer and gastric cancer. In recent years, various treatment options have been evaluated, such as bismuth-containing quadruple therapy, high-dose dual therapy, and the use of acid-suppressing drugs such as Vonoprazan, however, the effectiveness of eradication treatment is still dramatically decreasing due to the rising antibiotic resistance rate, and successful eradication of has become a major public health problem. Therefore a promising strategy against drug-resistant is to individualize treatment based on the outcome of antibiotic resistance. This article reviews the antibiotic resistance situation in recent years in various regions. The advantages and disadvantages of novel antibiotic resistance detection methods are examined, and the therapeutic efficacy of individualized therapy under different detection methods is evaluated. Molecular methods have developed rapidly in recent years, and non-invasive methods can quickly and accurately determine the presence of drug resistance. Clinical application of antibiotic resistance test results to guide medication use needs to be used as early as possible. Customized therapies based on antibiotic drug sensitivity testing and individualized therapies guided by personal medication history can contribute to future therapeutic strategies.
118Evaluation of guidelines for diagnosis and treatment of Helicobacter pylori infection.PubMed
Yan-Hong Ji, Yan-Mei Shi, Qian-Wen Hei, et al.
Helicobacter. 2023 Feb;28(1):e12937. doi: 10.1111/hel.12937. Epub 2022 Nov 21.
BACKGROUND: To systematically evaluate the quality of the guidelines for the diagnosis and treatment of Helicobacter pylori infection and to analyze the differences and reasons for the key recommendations in the guidelines. METHODS: Databases and websites were systematically searched to obtain guidelines for the diagnosis and treatment of Helicobacter pylori infection. Four independent reviewers used the Guideline Evaluation Tool (AGREE II) to evaluate the included guidelines. The intraclass correlation coefficient (ICC) and Fleiss' kappa coefficient were used to measure the consistency of evaluation guidelines between guide reviewers. Differences between guidelines and the reasons for the differences were analyzed by comparing the recommendations of different guidelines and the evidence supporting the recommendations. RESULTS: A total of 17 guidelines for Helicobacter pylori infection were included in this study. The AGREE II scores of these guidelines were low overall, with 4 of them had a score of over 60%, which indicates that the guidelines are recommended, and 13 of them having a score ranging from 30 to 60%, which indicates that the guidelines are recommended but need to be revised, while no guideline had a score of 30% or less, which indicates that they were not recommended. The analysis of these guidelines found that there were some differences in the main recommendations. Not all guidelines recommend sequential therapy as the recommended therapy. Whether bismuth quadruple therapy should be used as the recommended first-line therapy is unclear. The antibiotic resistance rate is different in different regions. Combined with the local antibiotic sensitivity test, the eradication rate of Helicobacter pylori can be improved. CONCLUSION: There are significant differences in the quality of Helicobacter pylori infection guidelines and the key recommendations. Improving the deficiencies of existing guidelines is an effective way to develop high-quality guidelines and make reasonable recommendations for the treatment of Helicobacter pylori infection in the future.
119Susceptibility-Guided Therapy vs. Bismuth-Containing Quadruple Therapy as the First-Line Treatment for Infection: A Systematic Review and Meta-Analysis.PubMed
Yaobin Ouyang, Wenjing Zhang, Chen He, et al.
Front Med (Lausanne). 2022 Mar 24;9:844915. doi: 10.3389/fmed.2022.844915. eCollection 2022.
BACKGROUND: The increased antibiotic resistance of () has led to the decreased efficacy of regimens. AIM: To evaluate the efficacy, safety, and compliance of susceptibility-guided therapy (SGT) vs. bismuth-containing quadruple therapy (BQT) as the first-line treatment for infection. MATERIALS AND METHODS: This meta-analysis was performed in accordance with the PRISMA 2009 guidelines. A systematic search in PubMed, Embase, and Cochrane databases was conducted using the combination of " or or ," "bismuth quadruple," and "tailored eradication OR tailored therapy OR susceptibility-guided therapy OR personalized therapy OR antibiotic susceptibility testing." RESULTS: Five studies with 2,110 infected patients were enrolled. The pooled eradication rates of SGT and BQT were 86 vs. 78% ( < 0.05) and 92 vs. 86% ( > 0.05) by intention-to-treat (ITT) and per-protocol (PP) analyses, respectively. SGT has a significantly superior efficacy than BQT [pooled risk ratio (RR) = 1.14, < 0.05] in a subgroup of cultures with the susceptibility test. The pooled side effect rate was 20% in SGT and 22% in BQT, which showed no significant difference ( > 0.05). The compliances of SGT and BQT were 95 and 92%, respectively. CONCLUSION: Compared with BQT, SGT showed a higher efficacy and similar safety as the first-line treatment of infection in areas with high antibiotic resistance. The decision-making of first-line regimens for infection should depend on the availability and cost-effectiveness of susceptibility tests and bismuth in local areas.
120Clinical evaluation of personalized treatment guided by PCR detection from fecal samples: a real-world study.PubMed
Ruolin Peng, Zhimei Zhang, Chuchu Yang, et al.
Front Cell Infect Microbiol. 2025 Apr 28;15:1519804. doi: 10.3389/fcimb.2025.1519804. eCollection 2025.
BACKGROUND: Growing antibiotic resistance in () diminishes eradication therapy effectiveness, emphasizing the need for accurate, non-invasive diagnostic techniques. This study aims to assess the clinical utility of PCR analysis of fecal samples for detecting antibiotic resistance in guiding personalized treatment for infection. METHODS: A retrospective, observational study was conducted across 13 hospitals within Jiangsu Province. Fecal samples were analyzed using fluorescence PCR for the and genes, indicating clarithromycin and levofloxacin resistance. Then, individualized eradication recommendations were proposed for the -positive patients. A follow-up was performed one year later to evaluate the eradication outcomes in a routine medical environment, with participants having provided informed consent. RESULTS: A total of 387 participants completed the eradication treatment, with an overall success rate of 91.0% (352/387, 95% CI: 87.6%-93.6%). Among them, 310 individuals received a 14-day course of bismuth quadruple therapy (BQT), achieving an eradication rate of 90.0% (279/310, 95% CI: 86.1%-93.1%). 77 participants were treated with high-dose dual therapy (HDDT) for the same duration, resulting in a slightly higher eradication rate of 94.8% (73/77, 95% CI: 87.2%-98.6%), although this difference was not statistically significant (=0.188). No significant differences in eradication rates were observed among various BQT antibiotic combinations (=0.208). The eradication rates for HDDT, based on either vonoprazan or esomeprazole, were 96.8% (61/63, 95% CI: 89.0%-99.6%) and 85.7% (12/14, 95% CI: 57.2%-98.2%), respectively, without a significant difference (=0.304). CONCLUSION: PCR detection from fecal samples targeting the resistance genes of is effective in guiding personalized treatments, highlighting its clinical utility and potential for broader application.
121Individualized diagnosis and eradication therapy for Helicobacter pylori infection based on gene detection of clarithromycin resistance in stool specimens: A systematic review and meta-analysis.PubMed
Xinlu Ren, Yanyan Shi, Baojun Suo, et al.
Helicobacter. 2023 Jun;28(3):e12958. doi: 10.1111/hel.12958. Epub 2023 Feb 24.
BACKGROUND: Empiric therapy for Helicobacter pylori infection results in significantly increased antibiotic resistance and decreased eradication efficacy. The genotypic testing of clarithromycin resistance from stool specimens is a promising method for individualized diagnosis and treatment. This study aimed to determine the status of research and application on this method through a systematic review and meta-analysis. METHODS: PubMed, Embase, MEDLINE, and WAN FANG database were searched for relevant literature. The quality of included diagnostic articles was evaluated using the quality Assessment of Diagnostic Accuracy Studies-2 tool. A bivariate random-effect model was conducted to calculate the diagnostic accuracy of genotypic testing of clarithromycin resistance. RESULTS: A total of 16 diagnostic-related were included and analyzed after exclusions. The pooled sensitivity and specificity of diagnostic meta-analysis were 0.93 (95% confidence interval [CI]: 0.90-0.96) and 0.98 (95% CI: 0.93-1.00), respectively. The area under the curve (AUC) of the summary receiver operating characteristic was 0.97 (95% CI: 0.95-0.98). The genotypic testing in stool samples had heterogeneous sensitivity (Q = 37.82, p < .01, I = 37.82) and specificity (Q = 60.34, p < .01, I = 93.72) in detecting clarithromycin resistance. Purification method, stool sample weight, real-time PCR, and antimicrobial susceptibility testing as reference accounted for the heterogeneity of pooled sensitivity, while patient age, purification method, stool sample weight, and real-time PCR for the heterogeneity of pooled specificity. CONCLUSION: The genotypic testing of clarithromycin resistance from stool specimens is an accurate, convenient, noninvasive, and rapid detection technology, providing a definitive diagnosis of clarithromycin resistance and guiding the rational antibiotic selection.
122Treatment strategies and pharmacist-led medication management for Helicobacter pylori infection.PubMed
Yu-Zhen Wang, Jie Chen, Shi-Qin Pei, et al.
Drug Dev Res. 2023 Apr;84(2):326-336. doi: 10.1002/ddr.22025. Epub 2022 Dec 26.
Half of the world's population is Helicobacter pylori carrier. Updated guidelines and consensus have been issued across regions with the main aim of reducing social transmission and increasing H. pylori eradication rate. Although alternative therapies including traditional Chinese medicine and probiotics have also been used to improve H. pylori eradication rate in clinical practice, current mainstream treatment is still dependent on triple and quadruple therapies that includes antibacterial agents (e.g., amoxicillin and furazolidone) and proton pump inhibitor. Researches also assessed the eradication rate of optimized high-dose dual therapy in treating H. pylori infection. With the increase of antibiotic resistance rate, the treatment strategies for H. pylori infection are constantly adjusted and improved. Besides, low medication compliance is another key influencing factor for H. pylori treatment failure. Emerging studies indicate that pharmacists' intervention and new pharmaceutical care methods can enhance patient medication compliance, reduce adverse drug reactions, and improve H. pylori eradication rate. The purpose of this review is to summarize the advances in treating H. pylori infection and highlight the necessity of developing novel strategies to cope with the increasing challenges and to achieve personalized medication. Also, this review attaches great importance to pharmacists in optimizing H. pylori treatment outcomes as a routine part of therapy.
123Screening and eradication of for gastric cancer prevention: the Taipei global consensus.PubMed
Jyh-Ming Liou, Peter Malfertheiner, Yi-Chia Lee, et al.
Gut. 2020 Dec;69(12):2093-2112. doi: 10.1136/gutjnl-2020-322368. Epub 2020 Oct 1.
OBJECTIVE: A global consensus meeting was held to review current evidence and knowledge gaps and propose collaborative studies on population-wide screening and eradication of for prevention of gastric cancer (GC). METHODS: 28 experts from 11 countries reviewed the evidence and modified the statements using the Delphi method, with consensus level predefined as ≥80% of agreement on each statement. The Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach was followed. RESULTS: Consensus was reached in 26 statements. At an individual level, eradication of reduces the risk of GC in asymptomatic subjects and is recommended unless there are competing considerations. In cohorts of vulnerable subjects (eg, first-degree relatives of patients with GC), a screen-and-treat strategy is also beneficial. eradication in patients with early GC after curative endoscopic resection reduces the risk of metachronous cancer and calls for a re-examination on the hypothesis of 'the point of no return'. At the general population level, the strategy of screen-and-treat for infection is most cost-effective in young adults in regions with a high incidence of GC and is recommended preferably before the development of atrophic gastritis and intestinal metaplasia. However, such a strategy may still be effective in people aged over 50, and may be integrated or included into national healthcare priorities, such as colorectal cancer screening programmes, to optimise the resources. Reliable locally effective regimens based on the principles of antibiotic stewardship are recommended. Subjects at higher risk of GC, such as those with advanced gastric atrophy or intestinal metaplasia, should receive surveillance endoscopy after eradication of . CONCLUSION: Evidence supports the proposal that eradication therapy should be offered to all individuals infected with . Vulnerable subjects should be tested, and treated if the test is positive. Mass screening and eradication of should be considered in populations at higher risk of GC.
124Screening and eradication of or gastric cancer prevention: Taipei Global Consensus II.PubMed
Jyh-Ming Liou, Peter Malfertheiner, Tzu-Chan Hong, et al.
Gut. 2025 Oct 8;74(11):1767-1791. doi: 10.1136/gutjnl-2025-336027.
OBJECTIVE: To convene a global consensus on () screening and eradication strategies for gastric cancer prevention, identify key knowledge gaps and outline future research directions. METHODS: 32 experts from 12 countries developed and refined consensus statements on management, using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework to assess evidence and the Delphi method to achieve ≥80% agreement. RESULTS: Consensus was achieved on 28 statements. Eradication of , the primary cause of gastric cancer, reduces the risk of gastric cancer across all age groups, with the greatest risk reduction before the onset of premalignant conditions. eradication also promotes ulcer healing, prevents ulcer recurrence and reduces the risk of NSAID/aspirin related ulcers. transmission primarily occurs within families, making family based approaches promising for reducing spread and improving treatment outcomes. screening should prioritise high risk populations. C-urea breath test or monoclonal stool antigen tests are preferred. Validated serological testing is a feasible alternative in low prevalence settings when followed by confirmatory non-serological testing. Integrating screening into existing health programmes may optimise patient adherence and resource utilisation. Empiric eradication treatment, especially bismuth quadruple therapy, is recommended in regions with high antibiotic resistance for conventional antibiotics. Potassium competitive acid blocker based regimens are alternatives. Confirmatory testing is strongly recommended to ensure eradication. Endoscopy is suggested for infected individuals with a high risk of gastric cancer and/or alarm features. eradication does not increase the risk of reflux oesophageal adenocarcinoma. Long term disruptions to the microbiota and resistome, as well as the environmental impact of increased antibiotic use, warrant further investigation. The development of an vaccine remains an unmet need, as does the establishment of a risk stratified approach informed by advanced genetic research. CONCLUSION: eradication is an effective prevention strategy for gastric cancer that should be offered to all infected adult individuals. Future research should prioritise determining the optimal timing for screening, evaluating long term individual and population outcomes, as well as identifying more precise risk stratification parameters.
125The eradication of Helicobacter pylori to prevent gastric cancer: a critical appraisal.PubMed
Jeng-Yih Wu, Yi-Chia Lee, David Y Graham
Expert Rev Gastroenterol Hepatol. 2019 Jan;13(1):17-24. doi: 10.1080/17474124.2019.1542299. Epub 2018 Nov 13.
Gastric cancer is one of the top causes of cancer-related death worldwide. How to eliminate gastric cancer is an urgent public-health issue. Areas covered: In this review, we present up-to-date results of studies on gastric cancer prevention through the eradication of Helicobacter pylori and discuss strategies and obstacles for the implementation of population-wide screening and treatment of this pathogen to prevent gastric cancer. Expert commentary: Gastric cancer is an inflammation-associated cancer with multistep carcinogenesis. The process consists of H. pylori infection, ongoing inflammation, development of metaplastic epithelia and genetic instability eventuating in gastric cancer. H. pylori infection is critical for development of the disease and studies have consistently shown that H. pylori eradication results in a reduction in (a) gastric mucosal inflammation, (b) progression of histologic damage, (c) risk of peptic ulcers and ulcer recurrence, and (d) risk of gastric cancer. Compared with a large number of clinical trials evaluating chemopreventive approaches, studies of population-wide screening, and eradication of H. pylori have only recently begun and only in high-risk populations. To eliminate gastric cancer requires information on how to implement an effective program for screening and treatment of H. pylori taking into consideration the other health priorities in any specific population.
126Effect of Helicobacter pylori Eradication on Gastric Cancer Prevention: Updated Report From a Randomized Controlled Trial With 26.5 Years of Follow-up.PubMed
Lingjun Yan, Ying Chen, Fa Chen, et al.
Gastroenterology. 2022 Jul;163(1):154-162.e3. doi: 10.1053/j.gastro.2022.03.039. Epub 2022 Mar 29.
BACKGROUND & AIMS: Helicobacter pylori infection is considered as the most important risk factor in the pathogenesis of gastric cancer. This study aims to evaluate the long-term effects of H pylori eradication treatment on the incidence and mortality of gastric cancer among a high-risk population. METHODS: This prospective, randomized, placebo-controlled trial was conducted in a high-risk area in southern China in July 1994. A total of 1630 asymptomatic, H pylori-infected individuals were randomly assigned to receive standard triple therapy for H pylori eradication (n = 817) or placebo (n = 813), and were followed up until December 2020. The primary outcome was incidence of gastric cancer. Total and cause-specific mortalities were the secondary outcomes. RESULTS: During 26.5 years of follow-up, 21 participants (2.57%) in the treatment arm and 35 (4.31%) in the placebo arm were diagnosed with gastric cancer. Participants receiving H pylori treatment had a lower incidence of gastric cancer compared with their placebo counterparts (hazard ratio [HR], 0.57; 95% CI, 0.33-0.98). More obvious risk reduction was observed among those without premalignant gastric lesions (HR, 0.37; 95% CI, 0.15-0.95) and those without dyspepsia symptoms at baseline (HR, 0.44; 95% CI, 0.21-0.94). Furthermore, compared with 32 cases of gastric cancer observed among 527 participants with persistent H pylori infection in the placebo group, only 16 were identified in 625 subjects with successful eradication in the treatment group (HR, 0.46; 95% CI, 0.26-0.83). However, there were no statistically significant differences for any mortality end points between the 2 groups. CONCLUSIONS: Eradication of H pylori might confer a long-term protection against gastric cancer in high-risk populations, especially for infected individuals without precancerous gastric lesions at baseline.
127Screening for Helicobacter pylori to Prevent Gastric Cancer: A Pragmatic Randomized Clinical Trial.PubMed
Yi-Chia Lee, Tsung-Hsien Chiang, Han-Mo Chiu, et al.
JAMA. 2024 Nov 19;332(19):1642-1651. doi: 10.1001/jama.2024.14887.
IMPORTANCE: Effects of screening for Helicobacter pylori on gastric cancer incidence and mortality are unknown. OBJECTIVE: To evaluate the effects of an invitation to screen for H pylori on gastric cancer incidence and mortality. DESIGN, SETTING, AND PARTICIPANTS: A pragmatic randomized clinical trial of residents aged 50 to 69 years in Changhua County, Taiwan, eligible for biennial fecal immunochemical tests (FIT) for colon cancer screening. Participants were randomized to either an invitation for H pylori stool antigen (HPSA) + FIT assessment or FIT alone. The study was conducted between January 1, 2014, and September 27, 2018. Final follow-up occurred December 31, 2020. INTERVENTION: Invitation for testing for H pylori stool antigen. MAIN OUTCOMES AND MEASURES: The primary outcomes were gastric cancer incidence and gastric cancer mortality. All invited individuals were analyzed according to the groups to which they were randomized. RESULTS: Of 240 000 randomized adults (mean age, 58.1 years [SD, 5.6]; 46.8% female), 63 508 were invited for HPSA + FIT, and 88 995 were invited for FIT alone. Of the 240 000 randomized, 38 792 who were unreachable and 48 705 who did not receive an invitation were excluded. Of those invited, screening participation rates were 49.6% (31 497/63 508) for HPSA + FIT and 35.7% (31 777/88 995) for FIT alone. Among 12 142 participants (38.5%) with positive HPSA results, 8664 (71.4%) received antibiotic treatment, and eradication occurred in 91.9%. Gastric cancer incidence rates were 0.032% in the HPSA + FIT group and 0.037% in the FIT-alone group (mean difference, -0.005% [95% CI, -0.013% to 0.003%]; P = .23). Gastric cancer mortality rates were 0.015% in the HPSA + FIT group and 0.013% in the FIT-alone group (mean difference, 0.002% [95% CI, -0.004% to 0.007%]; P = .57). After adjusting for differences in screening participation, length of follow-up, and patient characteristics in post hoc analyses, an invitation for HPSA + FIT was associated with lower rates of gastric cancer (0.79 [95% CI, 0.63-0.98]) but not with gastric cancer mortality (1.02 [95% CI, 0.73-1.40]), compared with FIT alone. Among participants who received antibiotics, the most common adverse effects were abdominal pain or diarrhea (2.1%) and dyspepsia or poor appetite (0.8%). CONCLUSIONS AND RELEVANCE: Among residents of Taiwan, an invitation to test for HPSA combined with FIT did not reduce rates of gastric cancer or gastric cancer mortality, compared with an invitation for FIT alone. However, when differences in screening participation and length of follow-up were accounted for, gastric cancer incidence, but not gastric cancer mortality, was lower in the HSPA + FIT group, compared with FIT alone. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01741363.
128Cost-Effectiveness of Screening Helicobacter pylori for Gastric Cancer Prevention: a Systematic Review.PubMed
Maryam Sarmasti, Manouchehr Khoshbaten, Farhad Khalili, et al.
J Gastrointest Cancer. 2022 Dec;53(4):1093-1103. doi: 10.1007/s12029-021-00726-7. Epub 2021 Oct 25.
Globally, prevalence of Helicobacter pylori is around 50%, and it has a directly proportional relationship with gastric cancer. Screening and treatment of Helicobacter pylori could reduce gastric cancer by 35%. Drawing on the scarce resources, it is reasonable to use the most cost-effectiveness Helicobacter pylori screening procedure. The purpose of this study was to evaluate Helicobacter pylori screening techniques and to specify the efficient technique from a cost-effectiveness perspective. This systematic review was conducted via searching electronic databases including Scopus, Embase, PubMed, Web of Science, and Cochrane Reviews. Our search retrieved 904 articles, of which, 606 full-text studies have been selected after duplicate removal. Next, the 25 articles were sorted based on eligibility criteria and quality appraisal; eventually, only eight studies have been included for analysis. We reported the incremental cost-effectiveness ratio (ICER) screening compared to non-screening and different screening strategies. Eight studies were identified and retained for the final analysis. In this study, when screening techniques were compared to no-screening, serology screening techniques showed to be cost-effective. The lowest ICER calculated was US$$1230 cost per life-year gained (LYG) and US$1500 cost per quality-adjusted life-year (QALY). However, determining the optimal strategy compared to other strategies was depended on parameters such as context-specific, type of cost, threshold, and perspective, and also, it influenced by the framework of the cost-effectiveness analysis.
129Cost-effectiveness of screening and treating Helicobacter pylori for gastric cancer prevention.PubMed
Iris Lansdorp-Vogelaar, Linda Sharp
Best Pract Res Clin Gastroenterol. 2013 Dec;27(6):933-47. doi: 10.1016/j.bpg.2013.09.005. Epub 2013 Sep 27.
Gastric cancer is the second leading cause of cancer-related death worldwide. A meta-analysis of seven randomized controlled trials concluded that Helicobacter pylori eradication reduces gastric cancer incidence by 35%. Current consensus is that H. pylori screening and treatment is cost-effective only in high-risk populations. This paper provides an up-to-date overview of the evidence for cost-effectiveness of H. pylori screening and treatment in different population settings and risk levels for H. pylori infection. Ten unique cost-effectiveness or cost-utility analyses were identified. All found that screening for H. pylori to prevent gastric cancer in the general population costs less than $50,000 per LYG. This finding was robust for differences in H. pylori prevalence, gender and ethnicity. Based on limited evidence, re-treatment (for treatment failure), repeated screening, limiting screening and treatment to those with the CagA phenotype, or universal treatment, does not appear to be cost-effective. However, most included studies failed to consider both the broader benefits as well as the adverse effects of widespread use of antibiotics for H. pylori.
130Cost-Effectiveness Analysis of the Helicobacter Pylori Screening Programme in an Asymptomatic Population in China.PubMed
Tianyu Feng, Zhou Zheng, Jiaying Xu, et al.
Int J Environ Res Public Health. 2022 Aug 13;19(16):9986. doi: 10.3390/ijerph19169986.
Objective The aim of this study was to investigate the cost-effectiveness of Helicobacter pylori () screening and eradication treatment in an asymptomatic population in China and to explore the most cost-effective screening protocol for . Method We used TreeAge 2019 to construct Markov models to assess the direct healthcare costs and quality-adjusted life years (QALYs) and the cost per year of life saved (YoLS) of three therapies, i.e., annual, triennial and five-yearly screening. Excess probabilities were derived from published high quality studies and Meta-analyses, and costs and utilities were derived from the Chinese Yearbook of Health Care Statistics and published studies. Incremental cost-effectiveness ratios (ICERs) were used to describe the results. The willingness-to-pay threshold was set at China's Gross National Product per capita. Result In the asymptomatic population, the ICER per QALYs gained was US$1238.47 and US$1163.71 for every three and five years of screening compared to the annual screening group; the ICER per YoLS gained was US$3067.91 and US$1602.78, respectively. Conclusion Screening for in asymptomatic populations in China and eradicating treatment for those who test positive is cost-effective. Increasing screening participation in asymptomatic populations is more effective than increasing the frequency of screening. From a national payer perspective, it is cost-effective to screen the general asymptomatic population in China for and to eradicate those who test positive. Individuals need to choose a screening programme that they can afford according to their financial situation.
131Cost-effectiveness analysis of different screening strategies for helicobacter pylori infection in Iran: A model-based evaluation.PubMed
Mahmood Yousefi, Satar Rezaei, Manouchehr Khoshbaten, et al.
Helicobacter. 2023 Dec;28(6):e13027. doi: 10.1111/hel.13027. Epub 2023 Oct 15.
BACKGROUND: The World Health Organization recommends assessing screening for helicobacter pylori infection to lower gastric cancer (GC) rates. Therefore, we carried out a study to evaluate the cost-effectiveness of different H. pylori screening approaches in Iran. MATERIALS AND METHODS: We used a Markov model with a 50-year time horizon and health system perspective to compare four H. pylori screening strategies (endoscopy, serology, urea breath test [UBT], stool antigen test [SAT]) to no screening in the population aged 20 years and older in Iran. Model parameters were extracted from primary data and published studies. Cost data also came from medical records of 120 patients at different stages of GC. We calculated costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) for each strategy. Probabilistic sensitivity analysis (PSA) using Monte Carlo simulation tested the model's robustness. All analyses were done in TreeAge Pro 2020. RESULTS: All screening strategies provided more QALYs compared to no screening. Base-case analysis found the UBT strategy was the most cost-effective, with an ICER of 101,106,261.5 Iranian rial (IRR) per QALY gained, despite being more costly. No screening and endoscopy were dominated strategies, meaning they had higher costs but provided fewer effectiveness compared to other options. PSA showed at a willingness-to-pay (WTP) threshold of 316,112,349 IRR (Iran's GDP per capita) per QALY, UBT was the optimal strategy in 57.1% of iterations. CONCLUSION: This cost-effectiveness analysis found that screening for H. pylori may be cost-effective in Iran. Among the 4 screening strategies examined, UBT was the most cost-effective approach. Further studies should do cost-effectiveness analyses for specific age groups to optimize the benefits achieved with limited resources.
132EFFECT OF PHARMACIST COUNSELING ON PATIENT MEDICATION COMPLIANCE AND HELICOBACTER PYLORI ERADICATION AMONG JORDANIAN OUTPATIENTS.PubMed
Aiman A Shoiab, Ali Alsarhan, Ashraf O Khashroum
Arq Gastroenterol. 2023 Jan-Mar;60(1):74-83. doi: 10.1590/S0004-2803.202301000-10.
BACKGROUND: To examine the impact of pharmacist counseling and follow-up on patient's medication compliance and Helicobacter Pylori (H. pylori) eradication and evaluate the efficiency of an eradication regimen consisting of Clarithromycin 500 mg, Amoxicillin 1 g, and Lansoprazole 30 mg, twice daily for 14 days. METHODS: Two hundred patients undergoing endoscopy and positive rapid urease tests were included in the present study. Patients were randomly divided into two groups: an intervention group (n=100) and a control group (n=100). The intervention patients obtained their medications from the hospital pharmacist and received sufficient counseling and follow-up. On the other hand, the control patients received their medications from another hospital pharmacist and went through the routine hospital procedure without good counseling and follow-up. RESULTS: The intervention resulted in a statistically significant improvement in outpatient compliance with medication (45.0% vs 27.5%; P<0.05) and eradication of H. pylori (28.5% vs 42.5%; P<0.05) among those patients. CONCLUSION: This study reflects the importance of pharmacist counseling and patient compliance to medication, as the patients who received pharmacist counseling exhibited perfect compliance to medication, which led to the successful eradication of H. pylori.
133Safety profile of eradication treatments: literature review and updated data of the European Registry on management (Hp-EuReg).PubMed
Irina Luzko, Olga P Nyssen, Leticia Moreira, et al.
Expert Opin Drug Saf. 2024 May;23(5):553-564. doi: 10.1080/14740338.2024.2338245. Epub 2024 Apr 3.
INTRODUCTION: (H. pylori), the most prevalent chronic infection globally, is the major cause of relevant diseases such as gastric cancer, leading to high morbidity and mortality worldwide. Several studies have focused on optimize eradication treatment through combination therapies and antibiotic resistance. However, the adverse events profile and its impact, as a primary outcome, remains underexplored.The aim of this review was to summarize the available data on the safety of the most common regimens for eradication and its impact on the compliance. AREAS COVERED: This review encompassed the published evidence from the years 2008 to 2023 regarding both the safety and compliance for most common H. pylori eradication regimens. The main sources for this review comprised MEDLINE, PubMed, and Cochrane electronic databases. Furthermore, it included a safety analysis of unpublished data from the European Registry on management (Hp-EuReg). EXPERT OPINION: Poor compliance is correlated with significantly lower cure rates, and this is a unique modifiable source of H. pylori treatment failure. Eradication treatments have become complex, involving multiple drugs and dosing intervals. Thus, patient education is crucial; doctors must explain to the patient about potential temporary and most often harmless side effects.
134Effects of New Media-Based Education on the Treatment of Helicobacter pylori Infection: Systematic Review and Meta-Analysis.PubMed
Wentao Fan, Yuwen Tao, Jinjin Shi, et al.
J Med Internet Res. 2025 Oct 23;27:e78387. doi: 10.2196/78387.
BACKGROUND: Helicobacter pylori (H. pylori) infection continues to pose a substantial global health burden. The eradication of H. pylori has been shown to substantially reduce the risk of gastric cancer. However, despite the availability of effective antimicrobial regimens, eradication rates remain suboptimal, largely due to poor patient adherence to treatment. The emergence of new media-based education (NME) offers an effective approach to enhancing patient understanding, engagement, and adherence, thereby improving the overall management of H. pylori treatment and follow-up care. OBJECTIVE: This meta-analysis aimed to assess the impact of NME interventions on H. pylori eradication rates, patient compliance, adverse events, and patient satisfaction. METHODS: We systematically searched PubMed, Embase, Web of Science, and the Cochrane Library from inception to February 2025. Eligible studies included randomized controlled trials (RCTs) and retrospective cohort studies comparing NME (eg, mobile apps, SMS text messages, and WeChat) with conventional education in patients with H. pylori infection. Studies were required to report at least one of the following outcomes: eradication rate, patient compliance, adverse events, and patient satisfaction. Two reviewers independently performed study selection, data extraction, and risk-of-bias assessment. Random-effects models were used to calculate pooled risk ratios (RRs) with 95% CIs. Subgroup analyses were conducted based on intervention type, therapy regimen, regional socioeconomic status, age group, and WeChat communication format. Sensitivity analyses tested the robustness of the pooled results. RESULTS: A total of 13 studies (n=11, 85% RCTs and n=2, 15% retrospective cohort studies) involving 2942 patients were included. Overall, NME significantly improved H. pylori eradication compared with conventional education (81.9% vs 67%; RR 1.22, 95% CI 1.11-1.33; P<.001). Subgroup analyses showed greater benefits in patients receiving quadruple therapy (P<.001), those aged ≤60 years (P=.03), populations from low- and middle-income countries (P<.001), and 14-day regimens (P<.001). Notably, WeChat-based interventions (P=.002), especially one-on-one education (P=.006), produced the most pronounced effects, whereas telephone- and messaging-based methods showed limited impact. Patient compliance was also significantly higher in the NME group (90.5% vs 73%; RR 1.27, 95% CI 1.15-1.40; P<.001), particularly among younger patients (P=.03) and in 14-day regimens (P<.001). In contrast, NME did not reduce adverse events (P=.23). Patient satisfaction, reported in 23% (3/13) of the studies, was consistently higher with NME (P<.001). Most RCTs (7/11, 64%) were judged to be at low risk of bias, and sensitivity analyses confirmed the robustness of all primary outcomes. CONCLUSIONS: NME significantly enhances H. pylori eradication and patient compliance without increased adverse events. Personalized and interactive communication platforms, especially WeChat-based interventions, show substantial promise. These findings support the integration of tailored digital education into clinical practice, particularly in resource-limited or technology-adopting settings. Further high-quality RCTs are warranted to validate long-term efficacy and generalizability. TRIAL REGISTRATION: PROSPERO CRD42024517954; https://www.crd.york.ac.uk/PROSPERO/view/CRD42024517954.
135The fourth Mexican consensus on Helicobacter pylori.PubMed
F J Bosques-Padilla, J M Remes-Troche, M S González-Huezo, et al.
Rev Gastroenterol Mex (Engl Ed). 2018 Jul-Sep;83(3):325-341. doi: 10.1016/j.rgmx.2018.05.003. Epub 2018 Jun 22.
Important advances have been made since the last Mexican consensus on the diagnosis and treatment of Helicobacter pylori (H. pylori) infection was published in 2007. Therefore, the Asociación Mexicana de Gastroenterología summoned 20 experts to produce "The Fourth Mexican Consensus on Helicobacter pylori". From February to June 2017, 4 working groups were organized, a literature review was performed, and 3 voting rounds were carried out, resulting in the formulation of 32 statements for discussion and consensus. From the ensuing recommendations, it was striking that Mexico is a country with an intermediate-to-low risk for gastric cancer, despite having a high prevalence of H. pylori infection. It was also corroborated that peptic ulcer disease, premalignant lesions, and histories of gastric cancer and mucosa-associated lymphoid tissue lymphoma should be considered clear indications for eradication. The relation of H. pylori to dyspeptic symptoms continues to be controversial. Eradication triple therapy with amoxicillin, clarithromycin, and a proton pump inhibitor should no longer be considered first-line treatment, with the following 2 options proposed to take its place: quadruple therapy with bismuth (proton pump inhibitor, bismuth subcitrate, tetracycline, and metronidazole) and quadruple therapy without bismuth (proton pump inhibitor, amoxicillin, clarithromycin, and metronidazole). The need for antimicrobial sensitivity testing when 2 eradication treatments have failed was also established. Finally, the promotion of educational campaigns on the diagnosis and treatment of H. pylori for both primary care physicians and the general population were proposed.
136Prevention of Gastric Cancer: Eradication of Helicobacter Pylori and Beyond.PubMed
Tetsuya Tsukamoto, Mitsuru Nakagawa, Yuka Kiriyama, et al.
Int J Mol Sci. 2017 Aug 3;18(8):1699. doi: 10.3390/ijms18081699.
Although its prevalence is declining, gastric cancer remains a significant public health issue. The bacterium is known to colonize the human stomach and induce chronic atrophic gastritis, intestinal metaplasia, and gastric cancer. Results using a Mongolian gerbil model revealed that infection increased the incidence of carcinogen-induced adenocarcinoma, whereas curative treatment of significantly lowered cancer incidence. Furthermore, some epidemiological studies have shown that eradication of reduces the development of metachronous cancer in humans. However, other reports have warned that human cases of atrophic metaplastic gastritis are already at risk for gastric cancer development, even after eradication of these bacteria. In this article, we discuss the effectiveness of eradication and the morphological changes that occur in gastric dysplasia/cancer lesions. We further assess the control of gastric cancer using various chemopreventive agents.