Long-term Risk of Upper Gastrointestinal Bleeding After Helicobacter pylori Eradication

A Population-based Cohort Study

Fang Jiang; Chuan-Guo Guo; Ka Shing Cheung; Wai K. Leung


Aliment Pharmacol Ther. 2021;54(9):1162-1169. 

In This Article

Abstract and Introduction


Background: The long-term effects of H. pylori eradication in preventing upper GI bleeding (UGIB) remains unknown.

Aim: To determine the long-term risks of UGIB after H. pylori eradication

Methods: We included all patients who had received clarithromycin-containing triple therapy for the treatment of H. pyliori infection between 2003 and 2012, without subsequent need for re-treatment. We included a propensity score (PS)-matched endoscopy cohort of H. pylori-negative patients as controls. The primary endpoint was the risk of subsequent UGIB. A multivariable Cox model was used to compute the hazard ratio (HR) of UGIB.

Results: We included 62 738 H. pylori-eradicated and 62 738 PS-matched H. pylori-negative patients, with a median follow-up of 8.1 years (IQR 5.5–10.6). The incidence of UGIB was 20.8 (95% CI 19.5–22.1) and 13.6 (95% CI 12.7–14.7) per 10 000 person-years in H. pylori-eradicated and H. pylori-negative patients, respectively. Compared to controls, H. pylori-eradicated patients had a significantly higher risk of UGIB (HR: 1.65, 95% CI 1.49–1.83). The risk of UGIB in H. pylori-eradicated patients increased after the first 2 years of follow up (HR: 2.18, 95% CI 1.91–2.49). Age-stratified analysis showed that patients >45 years had higher UGIB risk, even after eradication.

Conclusions: Despite H. pylori eradication, the long-term risk of UGIB was still higher than in H. pylori-negative control subjects. The protective effects of eradication therapy in preventing UGIB appeared to be limited to younger patients, and to within the first 2 years after eradication.


Gastrointestinal bleeding (GIB) is one of the most common causes of hospitalisation. In the United States, GIB was responsible for more than 500 000 hospitalisations and about 11 000 deaths in 2014. Specifically, upper GIB (UGIB) accounted for more than 200 000 hospitalisations and 4100 deaths, including mostly elderly patients.[1,2] Despite the declining incidences of UGIB,[3,4] an increased risk of UGIB is still observed in the elderly population, largely attributed to the presence of comorbidities and use of concurrent medications that heightened the bleeding risk.[5]

Helicobacter pylori (H. pylori) infection is the main cause of gastroduodenal diseases, including peptic ulcer disease and peptic ulcer bleeding.[6] It was estimated that nearly 50% of the global population were infected with H. pylori,[7] and the prevalence was reported to be the highest in developing regions such as Africa, South America and Western Asia,[8] particularly in the older population. Although the prevalence of H. pylori is also decreasing worldwide,[9] it is still causing a significant burden on the healthcare system due to the dense population in developing countries.

While H. pylori infection is a major cause of peptic ulcer disease,[10] peptic ulcer bleeding accounts for 31%-67% of all non-variceal UGIB.[11] Compelling evidences have shown that eradication of H. pylori infection could prevent recurrent peptic ulcer bleeding.[12,13] However, the long-term benefits of H. pylori eradication in reducing subsequent UGIB incidences in real-world setting remains uncertain. In particular, while UGIB is generally more prevalent in older patients, the age-stratified benefits of H. pylori eradication in preventing UGIB is unknown.

With the use of the population-based electronic medical record system in Hong Kong, we determined the long-term real-world benefits of H. pylori eradication in preventing non-variceal UGIB. We compared the long-term risk of UGIB in a large cohort of H. pylori eradicated patients with a matched cohort of H. pylori-negative patients, and further stratified the UGIB risk by the age of eradication.