S2550 Allopurinol Use Is Associated With Decreased Incidence of Hepatic Decompensation and Overall Mortality Among Adults With Compensated Cirrhosis: A Population-Based Propensity-Matched Cohort Study of 10,716 Individuals

Introduction: Recent studies highlight the potential role of allopurinol in reducing incident hepatic decompensation in compensated cirrhosis given its anti-inflammatory and anti-oxidant properties. The aim of this study was to evaluate the association of allopurinol use with incidence of hepatic decompensation and overall mortality in patients with compensated cirrhosis in a large, population-based propensity-matched cohort. Methods: Using a large electronic health-based database (TriNetX), we identified patients with compensated cirrhosis using International Classification of Diseases, Tenth Revision (ICD-10) codes. Allopurinol use was defined as having received allopurinol during ≥5 visits or hospital stays before follow-up and on or after cirrhosis diagnosis. Allopurinol use was assessed at: any dose, 100 mg and 300 mg. 1:1 propensity-score matching was done using demographics, labs, BMI, alcohol use, medical comorbidities, cirrhosis etiology, beta-blocker, opioid, benzodiazepine and statin use. The primary outcome was the incidence of composite hepatic decompensation [ascites, variceal bleeding, hepatic encephalopathy (HE), hepatorenal syndrome (HRS) or spontaneous bacterial peritonitis (SBP)]. Secondary outcomes included individual decompensation outcomes, hepatocellular carcinoma (HCC), and overall mortality. Outcomes were assessed at 6, 12, and 18 months. Results: After propensity-score matching, each group in the any dose exposure included 5358 patients, 2124 in each group for 100 mg, and 1020 in each group for 300 mg. At 18 months, statistically significantly lower incidence of hepatic decompensation was seen in the overall allopurinol exposure cohort (OR: 0.77; 95% CI: 0.70-0.84), the 100 mg cohort (OR: 0.66; 95% CI: 0.57 to 0.76), and 300 mg cohort (OR: 0.76, 95% CI: 0.62 to 0.94). Allopurinol exposure was associated with a decreased incidence of esophageal variceal bleeding (OR: 0.71 95% CI: 0.55 to 0.92), ascites (OR: 0.77 95% CI: 0.69 to 0.84), HE (OR: 0.76 95% CI: 0.63 to 0.92), SBP (OR: 0.61 95% CI: 0.46 to 0.80), and overall mortality (OR: 0.86 95%% CI: 0.77 to 0.96) compared to the control group. Conclusion: In a propensity-score matched analysis of a large national database, individuals with compensated cirrhosis and allopurinol use had significantly lower risk of hepatic decompensation and overall mortality. These findings suggest that allopurinol may play a potential role in managing cirrhosis. Future randomized clinical trials are needed to confirm these findings.