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.