Renin–angiotensin system inhibitors and fibrosis in chronic liver disease: a systematic review
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Background and aims
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.
KeywordsRenin–angiotensin system Hepatic fibrosis Systematic review Meta-analysis
Angiotensin receptor blocker
Angiotensin II type 1 receptor
Hepatitis C virus
Randomized controlled trial
Reactive oxygen stress
Standardized mean difference
Compliance with ethical standards
This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI15C2364), and also by the Yonsei University Future-Leading Research Initiative of 2014.
Conflict of interest
Gaeun Kim, Juyoung Kim, Yoo Li Lim, Moon Young Kim, and Soon Koo Baik declare that there are no conflicts of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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