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Microsc Res Tech. 2000 Mar 15;48(6):357-66.

Morphological changes of the human gastric mucosa under long-term proton pump inhibitor therapy and their clinical relevance.

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Department of Gastroenterology, Hepatology and Infectious Diseases, University of Tübingen, 72076 Tübingen, Germany.


Proton pump inhibitors are potent drugs for the treatment of acid-related diseases. The moderate hypergastrinaemia observed during therapy is a physiological response to low intragastric pH and the increase is limited to the first months of therapy with no further changes thereafter. Reports on endocrine cell changes in the antral mucosa under chronic PPI therapy are controversial and lack clinical relevance. In contrast, in the oxyntic mucosa hyperplastic argyrophil cell changes have been reported, dependent on the degree and duration of hypergastrinaemia, the severity of oxyntic mucosal gastritis, especially atrophy, and the presence of H. pylori infection. Current data do not support a progression from hyperplastic to dysplastic argyrophil cell lesions in humans in the absence of additional genetic factors. Data on the progression of oxyntic gastritis under chronic PPI treatment in comparison to untreated controls could not be confirmed in more recent studies including a well-matched control population. The main factor for gastritis progression is the presence of Helicobacter pylori infection. The bacterium not only causes a chronic inflammation of the gastric mucosa, resulting in atrophy and intestinal metaplasia, but also influences endocrine cell populations involved in the regulation of gastric acid secretion. The clinical benefit of H. pylori eradication in reflux esophagitis patients is still a matter of debate. The complex relations in humans between hypergastrinaemia, (oxyntic) gastritis and atrophy, H. pylori infection, argyrophil cell hyperplasia, and the effects of long-term PPI treatment of acid-related diseases do not allow a quantification of the contribution of each single factor for the observed changes.

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