The effects of angiotensin blocking agents on the progression of liver fibrosis in the HALT-C Trial cohort

Abstract

Background: Therapies that can slow the progression of liver fibrosis in chronic liver disease are needed. Evidence suggests that the renin-angiotensin system (RAS) contributes to inflammation and fibrosis in chronic liver disease. Both animal and limited human studies have shown that RAS inhibition with angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor-1 [AT-1] blockers (ARBs) has antifibrogenic properties.

Aims: In this study, we evaluated the effects of continuous ACEi/ARB use for 3.5 years on histological liver fibrosis progression in the HALT-C Trial cohort.

Methods: In the HALT-C Trial, subjects with chronic hepatitis C and advanced hepatic fibrosis (Ishak stage ≥3) underwent serial liver biopsies at baseline, 1.5 years, and 3.5 years after randomization. The primary outcome was a ≥2-point increase in Ishak fibrosis score in at least one of the two serial biopsies. Sixty-six subjects were continuously taking ACEi/ARBs over the observation period, 126 were taking other antihypertensive medications, and 343 subjects took no antihypertensive medications.

Results: The three groups were similar in baseline fibrosis scores, and the two groups being treated with antihypertensives were taking a similar number of antihypertensive medications. Fibrosis progression occurred in 33.3% of the ACEi/ARB group, 32.5% of the other antihypertensive medications group, and in 25.7% of subjects taking no antihypertensive medications. No significant associations between ≥2-point increases in fibrosis scores and continuous ACEi/ARB use were apparent at either 1.5 or 3.5 years in diabetes-adjusted and unadjusted odds ratios.

Conclusions: ACEi/ARB therapy did not retard the progression of hepatic fibrosis.