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World J Hepatol. Jun 28, 2015; 7(12): 1652-1659
Published online Jun 28, 2015. doi: 10.4254/wjh.v7.i12.1652
Systematic review: Preventive and therapeutic applications of metformin in liver disease
Aparna Bhat, Giada Sebastiani, Mamatha Bhat
Aparna Bhat, Giada Sebastiani, Mamatha Bhat, Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec H3A 1A1, Canada
Author contributions: Bhat A, Sebastiani G and Bhat M contributed to this paper.
Conflict-of-interest: The authors declare that they have no conflicts of interest to disclose related to this article.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Mamatha Bhat, MD, Division of Gastroenterology and Hepatology, McGill University Health Centre, 687 Pine Avenue West, Montreal, Quebec H3A 1A1, Canada. mamatha.bhat@mail.mcgill.ca
Telephone: +1-514-8431616 Fax: +1-514-8431421
Received: March 13, 2015
Peer-review started: March 16, 2015
First decision: April 27, 2015
Revised: May 5, 2015
Accepted: June 4, 2015
Article in press: June 8, 2015
Published online: June 28, 2015
Processing time: 107 Days and 19.2 Hours
Abstract

Metformin, a biguanide derivative, is the most commonly prescribed medication in the treatment of type 2 diabetes mellitus. More recently, the use of metformin has shown potential as a preventive and therapeutic agent for a broad spectrum of conditions, including liver disease and hepatic malignancies. In this systematic review, we critically analyze the literature behind the potential use of metformin across the spectrum of liver disease and malignancies. The PubMed and Ovid MEDLINE databases were searched from 2000 to March 2015, using a combination of relevant text words and MeSH terms: metformin and mammalian target of rapamycin, hepatitis B virus (HBV), hepatitis B virus (HCV), non-alcoholic fatty liver disease (NAFLD), hepatocellular carcinoma (HCC) or cholangiocarcinoma. The search results were evaluated for pertinence to the issue of metformin in liver disease as well as for quality of study design. Metformin has a number of biochemical effects that would suggest a benefit in treating chronic liver diseases, particularly in the context of insulin resistance and inflammation. However, the literature thus far does not support any independent therapeutic role in NAFLD or HCV. Nonetheless, there is Level III evidence for a chemopreventive role in patients with diabetes and chronic liver disease, with decreased incidence of HCC and cholangiocarcinoma. The use of metformin seems to be safe in patients with cirrhosis, and provides a survival benefit. Once hepatic malignancies are already established, metformin does not offer any therapeutic potential. In conclusion, there is insufficient evidence to recommend use of metformin in the adjunctive treatment of chronic liver diseases, including NAFLD and HCV. However, there is good evidence for a chemopreventive role against HCC among patients with diabetes and chronic liver disease, and metformin should be continued in patients even with cirrhosis to provide this benefit.

Keywords: Non-alcoholic fatty liver disease; Metformin; Chemoprevention; Hepatocellular carcinoma; Hepatitis C

Core tip: There has recently been a growing literature on the use of metformin as a potential preventive and therapeutic agent for various chronic liver diseases and hepatic malignancies. We therefore decided to review the efficacy of metformin across the spectrum of liver disease and malignancies. Based on our systematic review, there is insufficient evidence to recommend use of metformin in the adjunctive treatment of non-alcoholic fatty liver disease and hepatitis C. However, there is good evidence for a chemopreventive role against hepatocellular carcinoma among patients with diabetes and chronic liver disease, and metformin should be continued in patients even with cirrhosis to provide this benefit.