Association of <i>Helicobacter pylori </i>Treatment with Hepatic Encephalopathy Risk in Cirrhotic Patients: A Population-Based Cohort Study

Abstract

Background: Helicobacter pylori treatment may reduce the risk of hepatic encephalopathy (HE) by reducing ammonia production and changing the gut microbiota; however, a large-scale clinical study remains lacking. We aimed to investigate the effect of H. pylori treatment on HE risk through a cohort study. Methods: Using Taiwan's National Health Insurance Research Database from the years 1997 to 2011, 215,288 cirrhotic patients were screened. In order to avoid immortal time bias, patients in the H. pylori-treated and untreated cohorts were followed up from the last day of H. pylori treatment and the matched dates of starting their follow-up, respectively. After excluding patients aged < 18 years, those without underlying cirrhosis, those with an HE history, and those with any malignancies; 1,229 patients (the treated group) were randomly matched 1:2 with 2,458 patients (the untreated group) by means of propensity scores. Both cumulative incidences of, and hazard ratios (HRs) for, HE occurrence were analyzed after adjusting for competing mortality risk. Findings: The cumulative incidence of HE in the treated group was significantly lower than that in the untreated group after 1 year (3.00%, 95% confidence interval [CI]: 1.99-4.01 vs. 6.42%, 95% CI: 5.41-7.43), and after 3 years (6.33%, 95% CI: 4.82-7.85 vs. 11.21%, 95% CI: 9.84-12.58; P< 0.001). In multivariable regression analysis, H. pylori treatment was independently associated with a reduced HE risk (HR 0.54, 95% CI: 0.41-0.71; P< 0.001). Sensitivity subgroup analyses also verified this association, including those patients with (HR 0.53, 95% CI: 0.35-0.81) or without (HR 0.56, 95% CI: 0.39-0.81) liver decompensation. Interpretation: H. pylori treatment was significantly associated with a reduced risk of HE in cirrhotic patients. Funding Statement: The Ministry of Science and Technology (108-2321-B-075-002), National Yang-Ming University (107F-M01), the Ministry of Health and Welfare (MOHW108-TDU-B-211-124019), and Taipei Veterans General Hospital (V108E-004-1 and 107VACS-003), Taiwan. Declaration of Interests: The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript. Ethics Approval Statement: The Institutional Review Board of Taichung Veterans General Hospital approved the present study (CE19004B).