Graham D Y, Yamaoka Y
Department of Medicine, Veterans Affairs Medical Center, Baylor College of Medicine, Houston, TX 77030, USA.
Helicobacter. 1998 Sep;3(3):145-51. doi: 10.1046/j.1523-5378.1998.08031.x.
Helicobacter pylori infection is accepted to be associated with two mutually exclusive diseases: duodenal ulcer and gastric cancer. Attention has recently focused on possible relationships between H. pylori and gastroesophageal reflux disease and its complications such as adenocarcinoma of the gastric cardia. The aim of this study was to provide a framework for explaining the seemingly paradoxical associations between H. pylori and various gastrointestinal diseases.
Available data regarding H. pylori infection, cagA, acid secretion, corpus gastritis, and gastroesophageal reflux disease (GERD) and its complications are reviewed, and testable hypotheses are presented.
Linking the type of H. pylori (cagA-positive vs. cagA-negative), the pattern and intensity of inflammation, and acid secretion explains the apparent paradoxes in the associations between H. pylori and gastric cancer, duodenal ulcer, and GERD. Although H. pylori is inhibited by bile, a duodenal acid load sufficient to lower the average pH to precipitate bile acids overcomes that inhibition. H. pylori that contain a functional cag pathogenicity island produce a vigorous inflammatory response. The severity of mucosal inflammation predicts likelihood of different outcomes (e.g., in the bulb with likelihood of developing duodenal ulcer, and in the corpus with the degree of reduction in acid secretion and the rate of development of multifocal atrophic gastritis). Development of H. pylori corpus gastritis is promoted by profound inhibition of acid secretion (e.g., childhood infections or a high level of antisecretory therapy). The CagA protein, or the cagA gene, is a marker for enhanced inflammation, but CagA is not directly involved in the pathogenesis of gastric cancer or duodenal ulcer disease, nor is it a reliable indicator of the presence of a functional cag pathogenicity island.
The relationship between the type of H. pylori infection, presence or absence of a functional cag pathogenicity island, corpus inflammation, and acid secretion explains the duodenal ulcer/gastric cancer paradox and the relationship between H. pylori infection and the complications of GERD. The predicted rank order for the presence of GERD and its complications (peptic stricture, Barrett's esophagus, and adenocarcinoma of the gastric cardia) is highest in the population without H. pylori infection, less in those with H. pylori infection, and least in those infected with cagA-positive H. pylori. Controversy and confusing epidemiological observations will continue unless future studies provide data on the gastric corpus histology (or acid secretion) as well as regarding the presence or absence of a functional and intact cag pathogenicity island of the infecting organism.
幽门螺杆菌感染被认为与两种相互排斥的疾病相关：十二指肠溃疡和胃癌。最近，人们的注意力集中在幽门螺杆菌与胃食管反流病及其并发症（如贲门腺癌）之间可能存在的关系上。本研究的目的是提供一个框架，以解释幽门螺杆菌与各种胃肠道疾病之间看似矛盾的关联。
回顾了关于幽门螺杆菌感染、cagA、胃酸分泌、胃体胃炎以及胃食管反流病（GERD）及其并发症的现有数据，并提出了可检验的假设。
将幽门螺杆菌的类型（cagA阳性与cagA阴性）、炎症的模式和强度以及胃酸分泌联系起来，可以解释幽门螺杆菌与胃癌、十二指肠溃疡和GERD之间关联中明显的矛盾之处。虽然幽门螺杆菌会被胆汁抑制，但足以降低平均pH值以使胆汁酸沉淀的十二指肠酸负荷会克服这种抑制作用。含有功能性cag致病岛的幽门螺杆菌会引发强烈的炎症反应。黏膜炎症的严重程度预示着不同结局的可能性（例如，在十二指肠球部发生十二指肠溃疡的可能性，以及在胃体部胃酸分泌减少的程度和多灶性萎缩性胃炎的发展速度）。胃酸分泌受到深度抑制（如儿童期感染或高水平的抗分泌治疗）会促进幽门螺杆菌胃体胃炎的发展。CagA蛋白或cagA基因是炎症增强的标志物，但CagA并不直接参与胃癌或十二指肠溃疡病的发病机制，也不是功能性cag致病岛存在的可靠指标。
幽门螺杆菌感染的类型、功能性cag致病岛的有无、胃体炎症和胃酸分泌之间的关系解释了十二指肠溃疡/胃癌的矛盾以及幽门螺杆菌感染与GERD并发症之间的关系。GERD及其并发症（消化性狭窄、巴雷特食管和贲门腺癌）出现的预测排序在未感染幽门螺杆菌的人群中最高，在感染幽门螺杆菌的人群中较低，而在感染cagA阳性幽门螺杆菌的人群中最低。除非未来的研究提供关于胃体组织学（或胃酸分泌）以及感染生物体功能性和完整cag致病岛有无的数据，否则争议和令人困惑的流行病学观察将继续存在。
