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


OBJECTIVE
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.
Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. babudayyeh@partners.org
Barham K
BK
Abu Dayyeh
May
M
Yang
Jules L
JL
Dienstag
Raymond T
RT
Chung
D000328:Adult; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications*; D006801:Humans; D008103:Liver Cirrhosis / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors