A thirty-year war against Helicobacter pylori: a personal reflection

Abstract

The author personal results include therapeutic trials, the first Hungarian monograph on H. pylori, meta-analysis of the national and European eradication results and the first quality of life study in H. pylori-related functional dyspepsia. Less known are the interactions between H. pylori, carbonic anhydrase (CA) and its inhibitors. Gastric CA was described in 1939 by Horace W. Davenport. With the availability of acetazolamide in 1952 it was shown that it inhibits acid secretion in humans and dogs. Ioan Puca, from Szilágysomlyó, Romania, observed first, that in patients with chronic pulmonary obstructive disease, acetazolamide lead to a rapid healing of peptic ulcers. He patented in 1971 a drug containing acetazolamide + an electrolyte mixture named Ulcosilvanil and marketed it in Romania. Attempts to marketing it in Western countries were not successful; however, some trials were conducted in Hungary. Even the drug obtained high endoscopic healing and low recurrence rates of the peptic ulcers, the side effects and later, the development of H2 blockers and proton pump inhibitors led to its withdrawal in 1996. The author joined Puca's team between 1976–1990. To our greatest surprise, Sven Lindskog showed in 2002 that H. pylori expresses CA, which is inhibited by acetazolamide. Further, G. Sachs showed that CA is essential for the acid acclimation of H. pylori, while D. Y. Graham studied the effect of acetazolamide on H. pylori infection in vivo. These findings could explain the favorable effect of acetazolamide on peptic ulcer healing and the low recurrence rates found by us once upon a time. CA might either be a novel pharmacologic target, if specific inhibitors of the bacterial enzyme will be synthesized, or a potential antigen for vaccine development. For those presented above, the author considers that his fight against H. pylori lasted for thirty years: unfortunately, in the first 15 years, the enemy was not recognized.