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Metformin inhibits hepatitis B virus protein production and replication in human hepatoma cells
Author(s) -
Xun Y.H.,
Zhang Y.J.,
Pan Q.C.,
Mao R.C.,
Qin Y.L.,
Liu H.Y.,
Zhang Y.M.,
Yu Y.S.,
Tang Z.H.,
Lu M.J.,
Zang G.Q.,
Zhang J.M.
Publication year - 2014
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/jvh.12187
Subject(s) - hbsag , metformin , hepatitis b virus , hbeag , lamivudine , hepatitis b , cccdna , viral replication , virology , medicine , interferon , virus , immunology , biology , diabetes mellitus , endocrinology
Summary Hepatitis B virus surface antigen ( HB s A g) plays an important role in maintaining the tolerance and may interfere with host innate and adaptive immune responses; therefore, novel therapeutic strategies to reduce HB s A g loads in patients infected with hepatitis B virus ( HBV ) are emerging as an attractive but challenging issue. Metformin could regulate hepatic metabolism while the latter interacts with HBV infection. We hypothesized that metformin could affect HB s A g expression and HBV replication and may work synergistically when combined with current antivirals. In our study, a notably inhibitory effect on HB s A g production, as well as a moderate inhibition in HBV replication and HB e A g expression was observed following metformin treatment. The 50% effective concentration ( EC 50 ) for extracellular HB s A g and intracellular HB s A g in HBV ‐producing H ep G 2.2.15 cells was 2.85 m m and 2.75 m m , respectively, with a similarly selective index of about 18. When administered in combination, metformin enhanced the inhibitory effects of interferon‐α2b on HB s A g expression and HBV replication and provided a complimentary role in HB s A g expression for lamivudine ( LMV ). This novel action of metformin derives partially from its inhibition on multiple HBV cis ‐acting elements. By the virtues of preferably hepatocyte distribution and safety profile, collectively, our results suggest that metformin would be potentially clinically helpful as an HB s A g production inhibitor.