Ulcer recurrence after treatment of Helicobacter pylori infections
ACP J Club. 1992 July-Aug;117:24. doi:10.7326/ACPJC-1992-117-1-024
Graham DY, Lew GM, Klein PD, et al. Effect of treatment of Helicobacter pylori infection on the long-term recurrence of gastric or duodenal ulcer. A randomized, controlled study. Ann Intern Med. May
To determine recurrence of gastric and duodenal ulcers after treating Helicobacter pylori infections.
Cohort of patients with healed ulcers followed for up to 2 years.
A Veterans Affairs hospital.
109 participants (98% men; median age, 62 y) were recruited from 145 eligible patients (75%). All had H. pylori infections and either duodenal (n = 83) or gastric (n = 26) ulcers before treatment. Participants had been treated for 16 weeks with ranitidine (300 mg/d) alone or with ranitidine plus triple therapy (tetracycline HCl, 500 mg, 4 times/d, and metronidazole, 250 mg, 3 times/d, plus 5 or 8 tablets of bismuth subsalicylate over 2 wk) given to eradicate H. pylori. After ulcer healing, patients (ranitidine alone, 47; triple therapy, 62) were followed for ulcer recurrence. Patients took no antiulcer drugs. Nonsteroidal anti-inflammatory drugs (NSAIDs) were permitted.
Assessment of prognostic factors
H. pylori was measured by culture, breath test, immunoassay, and histologic tests 1 month after therapy and then every 3 months or if symptoms occurred.
Main outcome measures
An endoscopist, blinded to treatment status, did endoscopies every 3 months or if symptoms recurred. Ulcers were recorded by still video and defined as a circumscribed mucosal break ≥ 5 mm in diameter with apparent depth and covered by exudate.
After therapy H. pylori infections were found in all 47 patients in the ranitidine group but only 7 of 62 patients (11%) on triple therapy. Within 12 weeks, 24 (50%) of the ranitidine group had an ulcer recurrence, and by study end, 44 (94%) had had a recurrence. In the group receiving triple therapy, 10 patients (15%) had ulcer recurrence by 12 weeks and study end. After triple therapy, patients had a reduced probability of 1-year recurrence of duodenal ulcers (12%; 95% CI, 1% to 24%) and gastric ulcers (13%; CI, 4% to 31%) compared with patients who had been assigned to ranitidine (95%; CI, 84% to 100%, and 74%; CI, 44% to 100%, for duodenal and gastric ulcers, respectively) (P < 0.001 for difference between treatment groups). Ulcer recurrence in the triple therapy group was associated with persistence of H. pylori and use of NSAIDs.
Eradication of Helicobacter pylori in patients with duodenal or gastric ulcers is associated with decreased ulcer recurrence.
Sources of funding: Department of Veterans Affairs; National Institutes of Health; Department of Agriculture; Hilda Schwartz.
Address for article reprint: Dr. D.Y. Graham, Veterans Affairs Medical Center (111D), 2002 Holcombe Boulevard, Houston, TX 77030.
Medications currently used to treat peptic disease are extremely effective and have a remarkable record of safety. Unfortunately, these drugs control the disease without cure, and ulcer recurrence is the rule.
The evidence from previous studies that eradication of Helicobacter pylori healed ulcers raised the possibility that their natural history could be changed. Although the data were persuasive, additional information was necessary to help establish a causal relationship. A crucial part of that information is provided by Graham and his colleagues. They have shown that ulcer recurrence is extremely uncommon in men when H. pylori is eradicated. The only patients who developed new ulcers were taking NSAIDs or still harbored H. pylori. Therapy was equally effective for gastric and duodenal ulcers. Similar information has recently become available from several other groups.
Although the Graham study was methodologically strong, many questions remain. How long lasting is the remission? Will patients eventually become re-infected? Will antibiotic resistance be a problem? How frequent are complications and side effects, including potentially dangerous ones like pseudomembranous colitis? What is the optimal dose, combination, and duration of therapy? Why do most people infected with H. pylori never develop ulcers in the first place? Many of these questions are now being answered. It appears that a relatively short course of treatment (e.g., 2 weeks) is safe and effective. Shorter courses and lower doses may improve compliance and decrease side effects and cost.
Until these details are worked out, what should we do? We probably should not treat all ulcers with antibiotics because some will not recur. Patients with stubborn or complicated ulcers and patients scheduled for surgery would appear to be good candidates. The list of indications is likely to expand as we learn more about H. pylori.
Robert S. Sandler, MD, MPH
University of North Carolina Chapel Hill, North Carolina