Renin–angiotensin system inhibitors and fibrosis in chronic liver disease: a systematic review

The renin–angiotensin system (RAS) has an important role in hepatic fibrosis and portal hypertension. RAS inhibitors are already accepted in clinical fields for antihypertensive management, but their effects on hepatic fibrosis are controversial. The aim of this study was to systematically review the effects of RAS inhibitors on hepatic fibrosis based on histological assessment.

We performed a systematic review and meta-analysis (MA) of the literature using the Ovid-MEDLINE, EMBASE, and Cochrane Library databases (up to January 2015) to identify clinical studies evaluating the effects of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers on hepatic fibrosis or cirrhosis patients based on histological assessment. Of the 455 studies identified, we analyzed 7, including a total of 1066 patients, which met our selection criteria.

According to the MA, patients treated with RAS inhibitors had significantly lower fibrosis scores (SMD −0.68, 95 % CI −1.03, −0.34, I ² = 0 %, p < 0.0001) and smaller fibrosis areas (SMD −0.80, 95 % CI −1.18, −0.41, I ² = 0 %, p < 0.0001) than controls. Serum fibrosis markers such as TGF-β1, collagen I, IV, TIMP-1, and MMP2 were significantly reduced in the intervention group. In two studies, mean arterial pressures were significantly decreased in RAS inhibitor users, but there were no reports about symptoms related to decreased blood pressure. No significant difference was found in serum creatinine levels between the intervention and control groups, and significant renal dysfunction was not observed after administration of RAS inhibitors.

RAS inhibitors are potential therapeutic agents for hepatic fibrosis, which can be safely used in patients with chronic liver disease.