Helicobacter pylori and tolerance to H2-blockers.

Sirs, We read with great interest the recent paper by Fujisawa et al.1 showing that Helicobacter pylori infection prevents the occurrence of the tolerance phenomenon of histamine H2-receptor antagonists (H2RAs). They studied 20 healthy male volunteers who underwent 24-h intragastric pH-metry on the first and 15th day of administration of 20 mg b.d. famotidine and 10 mg b.d. lafutidine in a crossover fashion. The tolerance phenomenon was not observed in the seven H. pylori-positive subjects, whereas it occurred in the 13 H. pylori-negative ones. The Japanese Authors did not identify the precise mechanism responsible for this protection of H. pylori infection against the development of tolerance to H2RAs, although they excluded the possibility of H. pyloriinduced alteration of drug absorption and metabolism. They hypothesize that H. pylori-induced gastric mucosal atrophy may explain their findings, but this kind of histological abnormality capable of reducing gastric acid secretion was not assessed in their study and, more importantly, the mean age of their infected patients was 36.7 years, i.e. too young to permit the development of atrophy of oxyntic mucosa in all of them. Several years ago, we have published a study2 showing that tolerance was not found in a group of duodenal ulcer patients treated with a bedtime dose of roxatidine or ranitidine. At that time, we did not search for the presence of H. pylori infection, but we know that the germ has been detected in about 90% of duodenal ulcer patients and, therefore, we can suppose that almost all our patients were infected.3 Our results were in contrast with the demonstration of tolerance in virtually all studies that had been performed in healthy subjects,4–6 but were in agreement with the results achieved in duodenal ulcer patients by others7, 8 and are now confirmed by the findings of Fujisawa et al.1 in H. pylori-positive normal subjects. In contrast with the hypothesis of a reduction in gastric acid secretion as effect of H. pylori-induced mucosal atrophy, we believe that an increased antisecretory action of H2RAs may prevent the development of tolerance in infected individuals. A series of papers not quoted by the Japanese authors, have specifically addressed this point. In fact, it has been shown that omeprazole produces a greater decrease in gastric acid secretion in subjects with H. pylori infection than in those who are H. pylori-negative9 and the same effect has been later confirmed with the use of H2RAs in infected individuals, although to a lesser extent than with PPIs.10 So, it is possible that this greater acid suppression induced by H. pylori infection and probably due to the presence of neutralizing ammonia produced by the germ in the stomach11 further increases intragastric pH during treatment with antisecretory drugs. This effect may mask the occurrence of tolerance to H2RAs in infected subjects and, in keeping with our hypothesis, Labenz et al.10 have shown that the intragastric pH during treatment with ranitidine depends on H. pylori infection and the tolerance to H2RAs develops after eradication of the germ.