Abstract
Renin-angiotensin system (RAS) inhibitors, including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs), have been associated with improved outcomes in metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to assess the differential impact of ACEIs versus ARBs on survival and cardiovascular outcomes in individuals with MASLD. Using data from the UK Biobank, we identified 52,143 participants with exclusive use of either an ACEI or ARB. Individuals with viral, autoimmune, cholestatic, or alcohol-related liver disease were excluded. MASLD was defined as fatty liver index ≥ 60 with ≥1 cardiometabolic risk factor. Inverse probability of treatment weighting (IPTW) was used to adjust for confounders. Outcomes included all-cause mortality, cardiovascular events, hepatic decompensation, and hepatocellular carcinoma (HCC), analyzed using Cox proportional hazards models. Among MASLD participants, ARB use was associated with significantly lower all-cause mortality compared to ACEI use (HR, 0.94; 95% CI, 0.90-1.00; p = 0.031) after IPTW adjustment. Cardiovascular risk was also lower with ARBs (HR, 0.92; 95% CI, 0.89-0.96; p < 0.001), particularly in subgroups with BMI ≥ 25 kg/m2, no diabetes, and advanced fibrosis. No differences in hepatic decompensation or HCC incidence were observed. Benefits of ARBs were not significant in participants without steatotic liver disease. ARB use was associated with improved survival and reduced cardiovascular events in individuals with MASLD, whereas ACEIs expressed no comparable benefit. These findings suggest that ARBs might be a more effective RAS inhibitor subclass in MASLD and support their preferential use in patients with steatotic liver disease requiring antihypertensive therapy.