title: Renin-angiotensin system inhibitors and fibrosis in chronic liver disease: a systematic review.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  RAS inhibitors are potential therapeutic agents for hepatic fibrosis, which can be safely used in patients with chronic liver disease.
authors.affiliation: Research Institute for Nursing Science, College of Nursing, Keimyung University, Dalgubeoldae-ro 1095, Dalseo-Gu, Daegu, 704-701, Republic of Korea.
authors.forename: Gaeun
authors.initials: G
authors.lastname: Kim
authors.affiliation: Research Institute for Nursing Science, College of Nursing, Keimyung University, Dalgubeoldae-ro 1095, Dalseo-Gu, Daegu, 704-701, Republic of Korea.
authors.forename: Juyoung
authors.initials: J
authors.lastname: Kim
authors.affiliation: Cell Therapy and Tissue Engineering Center, Wonju College of Medicine, Yonsei University, Ilsan-ro 20, Wonju, Gangwon-do, 220-701, Republic of Korea.|Department of Internal Medicine, Wonju College of Medicine, Yonsei University, Ilsan-ro 20, Wonju, Gangwon-do, 220-701, Republic of Korea.
authors.forename: Yoo Li
authors.initials: YL
authors.lastname: Lim
authors.affiliation: Cell Therapy and Tissue Engineering Center, Wonju College of Medicine, Yonsei University, Ilsan-ro 20, Wonju, Gangwon-do, 220-701, Republic of Korea.|Department of Internal Medicine, Wonju College of Medicine, Yonsei University, Ilsan-ro 20, Wonju, Gangwon-do, 220-701, Republic of Korea.
authors.forename: Moon Young
authors.initials: MY
authors.lastname: Kim
authors.affiliation: Cell Therapy and Tissue Engineering Center, Wonju College of Medicine, Yonsei University, Ilsan-ro 20, Wonju, Gangwon-do, 220-701, Republic of Korea. baiksk@yonsei.ac.kr.|Department of Internal Medicine, Wonju College of Medicine, Yonsei University, Ilsan-ro 20, Wonju, Gangwon-do, 220-701, Republic of Korea. baiksk@yonsei.ac.kr.
authors.forename: Soon Koo
authors.initials: SK
authors.lastname: Baik
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003401:Creatine / Q000097:blood; D006801:Humans; D008107:Liver Diseases / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D003401:Creatine
keywords: Hepatic fibrosis; Meta-analysis; Renin–angiotensin system; Systematic review