Do ACE Inhibitors and ARBs Improve Liver Outcomes in MASLD?- Hepatology Feb.26

Metabolic dysfunction–associated steatotic liver disease (MASLD) is tightly linked to cardiometabolic comorbidities, particularly hypertension. While blood pressure control is essential for cardiovascular risk reduction, whether antihypertensive drug choice influences liver-related outcomes has remained uncertain. This commentary reviews new evidence evaluating the potential role of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in MASLD.

Using a large U.S. insurance database and a target trial emulation approach, Ng and colleagues compared MASLD patients newly started on ACEI/ARB with those started on calcium channel blockers. The analysis suggested that ACEI/ARB use was associated with a lower risk of major adverse liver outcomes, including hepatic decompensation, as well as fewer cardiovascular events. These findings align with preclinical data showing antifibrotic effects of renin–angiotensin system inhibition and support the concept that systemic metabolic therapies may influence liver disease progression.

However, important limitations temper interpretation. As with all observational studies, residual confounding cannot be excluded, and the apparent cardiovascular advantage of ACEI/ARB over calcium channel blockers contrasts with results from randomized cardiovascular trials. Differences from prior Asian cohort studies—particularly regarding hepatocellular carcinoma risk—highlight how disease definitions, competing liver etiologies, and study design can influence results. In addition, the lack of granular fibrosis markers and treatment adherence data limits causal inference.

In summary, ACEI/ARB therapy may offer dual cardiovascular and hepatic benefit in MASLD, but the evidence remains indirect. Until randomized trials are available, antihypertensive selection should prioritize established cardiovascular and renal indications, within a holistic strategy to manage metabolic risk in MASLD patients.