Improved survival and reduced alcohol-associated hepatitis risk with renin-angiotensin-aldosterone system inhibitors in alcohol-associated liver disease

Background: Alcohol-associated liver disease (ALD) is a leading cause of liver-related mortality and is increasingly recognized for its contribution to cardiovascular diseases. The renin-angiotensin-aldosterone system (RAAS), including angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB), has demonstrated benefits in modulating inflammatory pathways. Clinical data regarding the effects in patients with ALD remain limited. Methods: We conducted a retrospective cohort study utilizing the TriNetX platform. Patients with ALD who were prescribed ACEI/ARB were compared with those prescribed calcium channel blockers (CCB). Propensity score matching (1:1) was applied to balance baseline characteristics. The primary outcome was all-cause mortality. Secondary outcomes included alcohol-associated hepatitis (AH), major adverse cardiovascular events (MACE), major adverse liver outcomes (MALO), and sepsis. Patients were followed for 5 years. Cox proportional hazards models were used to estimate hazard ratios (HR) with 95% confidence intervals (CI). Results: After matching, 7884 patients were included (3942 per group). ACEI/ARB use was associated with a significantly lower risk of all-cause mortality (HR: 0.70, 95% CI: 0.64–0.78, p < 0.001) compared with CCB use. Furthermore, the ACEI/ARB cohort demonstrated significant risk reductions across all secondary outcomes, including MACE (HR: 0.69, 95% CI: 0.61–0.77, p < 0.001), MALO (HR: 0.81, 95% CI: 0.73–0.90, p < 0.001), AH (HR: 0.88, 95% CI: 0.80–0.97, p = 0.008), and sepsis (HR: 0.61, 95% CI: 0.53–0.70, p < 0.001). Conclusions: In this large real-world cohort, ACEI/ARB use in patients with ALD was associated with reduced risks of mortality, cardiovascular events, liver events, AH, and sepsis, supporting a potential protective role of RAAS inhibition in ALD patients.