Watch Out for H pylori-Negative Ulcers High Incidence of Mortality and Recurrent Bleeding in Patients With Helicobacter pylori-Negative Idiopathic Bleeding

Background: Risk of recurrent bleeding from Helicobacter pylori-negative ulcers is greater than for H pylori ulcers, but to what degree is unknown. Objective: To determine the risk of rebleeding for peptic ulcers with and without associated H pylori infection. Design: Prospective cohort study in 1 institution over 7 years. Participants: 120 patients had H pylori-negative peptic ulcer bleeding and 213 had bleeding associated with H pylori infection. Methods: H pylori-negative patients had to have no exposure to NSAIDs, aspirin, or other medications within 4 weeks of the bleeding episode, negative results for H pylori on biopsies and the urease test taken during index endoscopy for bleeding, and no other evident cause of ulceration. Both groups were treated appropriately. Follow-up endoscopy was done to document healing. No long-term gastroprotective therapy was used. Primary end point was recurrent bleeding. Mortality was a secondary end point. Interventions: All patients had endoscopy for recurrent bleeding. Biopsies and urease test were also repeated during recurrent bleeding episodes. Drugs associated with gastric injury were prohibited during the study period. Results: H pylori-negative ulcer patients were older, had more gastric ulcers, and had more recurrent bleeding during the index hospitalization. Median follow-up was 30 months (range, 1 to 89 months) in H pylori-negative patients and 79 months (range, 1 to 89 months) in H pylori-positive patients. The 7-year cumulative rebleeding rate for H pylori-negative patients was 42% compared to 11% for H pylori-positive patients. When NSAID use and recurrent H pylori infection were excluded, the recurrent bleeding rate was 25% versus 3%. Mortality was higher in H pylori-negative patients and only correlated with American Society of Anesthesiology grade ≥3. H pylori-negative status was an independent predictor of recurrent bleeding and mortality. Conclusions: H pylori-negative bleeding ulcers are associated with an increased risk of rebleeding and mortality compared to H pylori-positive bleeding ulcers. Reviewer's Comments: Very interesting long-term study of patients with peptic ulcers that bled. Groups were followed based on presence of H pylori infection at the time their ulcer bled. The recurrent bleeding rate was significantly higher among patients who did not have H pylori infection. The rebleeding rate was extremely low for H pylori-positive patients after H pylori eradication unless recurrent infection occurred or NSAID use was documented. The shorter follow-up among H pylori-negative is explained by the higher mortality rate. Age could be a factor for recurrent bleeding, although this did not appear to be true based on statistical analysis. The authors make a strong case that H pylori-negative ulcers are different. They suggest that long-term gastroprotective treatment should be considered. (Reviewer-John A. Weigelt, MD).