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

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-beta 1, 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.