HELICOBACTER PYLORI, zyxwvu PART zyxwvu I1 0889%3553/00 $15.00 zy + .OO THE NONSTEROIDAL ANTI- INFLAMMATORY DRUGS CONTROVERSY Neville D. Yeomans, MD, George Garas, MBBS, and Christopher J. Hawkey, DM There is broad agreement that there are just two common causes of peptic ulcers in humans at present: infection with Helicobacter pylori and exposure of the gastric and duodenal mucosae to nonsteroidal anti-inflammatory drugs (NSAIDs). In both instances, superficial damage to the mucosa occurs in all exposed individuals, leading to cycles of damage and repair in the face of a fairly hostile luminal environment containing high concentrations of hydrogen ions and a potent proteolytic enzyme (pepsin). Usually the repair of the superfi- cial injury is rapid and successful, but occasionally, at some focal site, it fails, and an ulcer is the result. The discovery that most peptic ulcers were related to either H. pylori or NSAIDs is now well known,44 but NSAIDs were known to cause acute gastric bleeding in animals as early as the 1 9 3 0 ~ ~ ~ and acute gastroduodenal injury in humans in 1938.13 The first report suggesting that aspirin causes gastric ulcer in humans came from Douglas and Johnston12 in rural Queensland in 1961. Given the importance of these two risk factors for ulcers, it might be expected that patients who have been exposed to both would be at an increased overall risk of ulceration. The two theoretically could combine in any of the ways shown in Table 1. This article reviews the evidence that might underpin each of these possibilities and concludes that the relationship between H. pylori and NSAIDs as partners in ulcerogenesis is far from simple. The evidence is considered under the following headings: (1) prevalence of H. pylori infection in NSAID users, (2) prevalence of gastroduodenal injury in patients exposed to NSAIDs or H. pylori, (3) risk for ulcer bleeding when both risk factors are present, zyxwv (4) information about the ease of healing and preventing This work was supported, in part, by grants from the National Health and Medical Research Council of Australia. From the Departments of Medicine (NDY, GC) and Gastroenterology (NDY), The Univer- sity of Melbourne, Western Hospital, Melbourne, Australia; and the Department of Gastroenterology, University Hospital and Nottingham University, Nottingham, United Kingdom (CJH) GASTROENTEROLOGY CLINICS OF NORTH AMERICA VOLUME 29 - NUMBER zyxwvut 4 DECEMBER 2000 791