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.
RCT Entities:
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.
Authors: J R Jonsson; A D Clouston; Y Ando; L I Kelemen; M J Horn; M D Adamson; D M Purdie; E E Powell Journal: Gastroenterology Date: 2001-07 Impact factor: 22.682
Authors: K Ishak; A Baptista; L Bianchi; F Callea; J De Groote; F Gudat; H Denk; V Desmet; G Korb; R N MacSween Journal: J Hepatol Date: 1995-06 Impact factor: 25.083
Authors: Ramón Bataller; Erwin Gäbele; Robert Schoonhoven; Terry Morris; Mark Lehnert; Liu Yang; David A Brenner; Richard A Rippe Journal: Am J Physiol Gastrointest Liver Physiol Date: 2003-05-28 Impact factor: 4.052
Authors: Yong-Han Paik; Jonghwa Kim; Tomonori Aoyama; Samuele De Minicis; Ramon Bataller; David A Brenner Journal: Antioxid Redox Signal Date: 2014-01-24 Impact factor: 8.401