Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Virginia Commonwealth University and Central Virginia Veterans Healthcare System, Richmond, VA, USA.
Department of Hepatology, Institute for Liver and Biliary Sciences, New Delhi, India.
Lancet Gastroenterol Hepatol. 2023 Jul;8(7):611-622. doi: 10.1016/S2468-1253(23)00098-5. Epub 2023 May 22.
Cirrhosis, the end result of liver injury, has high mortality globally. The effect of country-level income on mortality from cirrhosis is unclear. We aimed to assess predictors of death in inpatients with cirrhosis using a global consortium focusing on cirrhosis-related and access-related variables.
In this prospective observational cohort study, the CLEARED Consortium followed up inpatients with cirrhosis at 90 tertiary care hospitals in 25 countries across six continents. Consecutive patients older than 18 years who were admitted non-electively, without COVID-19 or advanced hepatocellular carcinoma, were enrolled. We ensured equitable participation by limiting enrolment to a maximum of 50 patients per site. Data were collected from patients and their medical records, and included demographic characteristics; country; disease severity (MELD-Na score); cirrhosis cause; medications used; reasons for admission; transplantation listing; cirrhosis-related history in the past 6 months; and clinical course and management while hospitalised and for 30 days post discharge. Primary outcomes were death and receipt of liver transplant during index hospitalisation or within 30 days post discharge. Sites were surveyed regarding availability of and access to diagnostic and treatment services. Outcomes were compared by country income level of participating sites, defined according to World Bank income classifications (high-income countries [HICs], upper-middle-income countries [UMICs], and low-income or lower-middle-income countries [LICs or LMICs]). Multivariable models controlling for demographic variables, disease cause, and disease severity were used to analyse the odds of each outcome associated with variables of interest.
Patients were recruited between Nov 5, 2021, and Aug 31, 2022. Complete inpatient data were obtained for 3884 patients (mean age 55·9 years [SD 13·3]; 2493 (64·2%) men and 1391 (35·8%) women; 1413 [36·4%] from HICs, 1757 [45·2%] from UMICs, and 714 [18·4%] from LICs or LMICs), with 410 lost to follow-up within 30 days after hospital discharge. The number of patients who died while hospitalised was 110 (7·8%) of 1413 in HICs, 182 (10·4%) of 1757 in UMICs, and 158 (22·1%) of 714 in LICs and LMICs (p<0·0001), and within 30 days post discharge these values were 179 (14·4%) of 1244 in HICs, 267 (17·2%) of 1556 in UMICs, and 204 (30·3%) of 674 in LICs and LMICs (p<0·0001). Compared with patients from HICs, increased risk of death during hospitalisation was found for patients from UMICs (adjusted odds ratio [aOR] 2·14 [95% CI 1·61-2·84]) and from LICs or LMICs (2·54 [1·82-3·54]), in addition to increased risk of death within 30 days post discharge (1·95 [1·44-2·65] in UMICs and 1·84 [1·24-2·72] in LICs or LMICs). Receipt of a liver transplant was recorded in 59 (4·2%) of 1413 patients from HICs, 28 (1·6%) of 1757 from UMICs (aOR 0·41 [95% CI 0·24-0·69] vs HICs), and 14 (2·0%) of 714 from LICs and LMICs (0·21 [0·10-0·41] vs HICs) during index hospitalisation (p<0·0001), and in 105 (9·2%) of 1137 patients from HICs, 55 (4·0%) of 1372 from UMICs (0·58 [0·39-0·85] vs HICs), and 16 (3·1%) of 509 from LICs or LMICs (0·21 [0·11-0·40] vs HICs) by 30 days post discharge (p<0·0001). Site survey results showed that access to important medications (rifaximin, albumin, and terlipressin) and interventions (emergency endoscopy, liver transplantation, intensive care, and palliative care) varied geographically.
Inpatients with cirrhosis in LICs, LMICs, or UMICs have significantly higher mortality than inpatients in HICs independent of medical risk factors, and this might be due to disparities in access to essential diagnostic and treatment services. These results should encourage researchers and policy makers to consider access to services and medications when evaluating cirrhosis-related outcomes.
National Institutes of Health and US Department of Veterans Affairs.
肝硬化是肝脏损伤的终末结果，在全球范围内具有高死亡率。国家收入对肝硬化死亡率的影响尚不清楚。我们旨在使用专注于肝硬化相关和获取相关变量的全球联盟，评估肝硬化患者住院患者死亡的预测因素。
在这项前瞻性观察性队列研究中，CLEARED 联盟在六大洲 25 个国家的 90 家三级护理医院对肝硬化住院患者进行了随访。招募了年龄大于 18 岁、非择期入院、无 COVID-19 或晚期肝细胞癌的连续患者。我们通过限制每个站点最多招收 50 名患者，以确保公平参与。从患者及其病历中收集数据，包括人口统计学特征；国家；疾病严重程度（MELD-Na 评分）；肝硬化病因；使用的药物；入院原因；移植名单；过去 6 个月内的肝硬化病史；以及住院期间和出院后 30 天的临床过程和管理。主要结局是死亡和在索引住院期间或出院后 30 天内接受肝移植。对站点进行了关于诊断和治疗服务的可用性和获取情况的调查。根据世界银行的收入分类（高收入国家[HICs]、中上收入国家[UMICs]和低收入或中下收入国家[LICs 或 LMICs]），按参与站点的收入水平对国家进行分层，并比较了这些国家的结果。使用多变量模型，控制人口统计学变量、疾病病因和疾病严重程度，分析与感兴趣的变量相关的每个结局的可能性。
患者于 2021 年 11 月 5 日至 2022 年 8 月 31 日期间被招募。共获得 3884 名患者的完整住院数据（平均年龄 55.9 岁[标准差 13.3]；2493 名[64.2%]为男性，1391 名[35.8%]为女性；1413 名[36.4%]来自 HICs，1757 名[45.2%]来自 UMICs，714 名[18.4%]来自 LICs 或 LMICs），其中 410 名患者在出院后 30 天内失访。住院期间死亡的患者人数为 110 例（7.8%），其中 1413 例来自 HICs，1757 例来自 UMICs，714 例来自 LICs 和 LMICs（p<0.0001），出院后 30 天内死亡的患者人数为 179 例（14.4%），其中 1244 例来自 HICs，1556 例来自 UMICs，674 例来自 LICs 和 LMICs（p<0.0001）。与来自 HICs 的患者相比，来自 UMICs（调整后的优势比[aOR]2.14[95%置信区间 1.61-2.84]）和来自 LICs 或 LMICs（aOR 2.54[1.82-3.54]）的患者住院期间死亡的风险增加，出院后 30 天内死亡的风险也增加（UMICs 为 1.95[1.44-2.65]，LICs 或 LMICs 为 1.84[1.24-2.72]）。在 HICs 的 1413 名患者中，有 59 名（4.2%）接受了肝移植，在 UMICs 的 1757 名患者中有 28 名（1.6%）（aOR 0.41[95%置信区间 0.24-0.69]），在 LICs 和 LMICs 的 714 名患者中有 14 名（2.0%）（aOR 0.21[0.10-0.41]）接受了肝移植，而在索引住院期间（p<0.0001），在 HICs 的 1137 名患者中有 105 名（9.2%）接受了肝移植，在 UMICs 的 1372 名患者中有 55 名（4.0%）（aOR 0.58[0.39-0.85]），在 LICs 或 LMICs 的 509 名患者中有 16 名（3.1%）（aOR 0.21[0.11-0.40]）（p<0.0001），出院后 30 天内接受肝移植。站点调查结果显示，重要药物（利福昔明、白蛋白和特利加压素）和干预措施（紧急内镜检查、肝移植、重症监护和姑息治疗）的获取存在地域差异。
与 HICs 中的患者相比，来自 LICs、LMICs 或 UMICs 的肝硬化住院患者的死亡率明显更高，而与医疗风险因素无关，这可能是由于获得基本诊断和治疗服务的机会不均等所致。这些结果应鼓励研究人员和政策制定者在评估肝硬化相关结局时考虑服务和药物的获取情况。
美国国立卫生研究院和美国退伍军人事务部。
