Do hepatitis B virus and hepatitis C virus co-infections increase hepatocellular carcinoma occurrence through synergistically modulating lipogenic gene expression?
Article first published online: 4 APR 2012
© 2012 The Japan Society of Hepatology
Volume 42, Issue 8, pages 733–740, August 2012
How to Cite
Wu, Q. and Liu, Q. (2012), Do hepatitis B virus and hepatitis C virus co-infections increase hepatocellular carcinoma occurrence through synergistically modulating lipogenic gene expression?. Hepatology Research, 42: 733–740. doi: 10.1111/j.1872-034X.2012.00994.x
- Issue published online: 8 JUL 2012
- Article first published online: 4 APR 2012
- Accepted manuscript online: 2 MAR 2012 05:11AM EST
- Received 3 January 2012; revision 7 February 2012; accepted 27 February 2012.
- hepatitis B virus and hepatitis C virus co-infection and hepatocellular carcinoma;
- peroxisome proliferator-activated receptors;
- PI3K/PTEN/Akt signaling pathway;
- sterol regulatory element-binding proteins;
- unfolded protein response
Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections cause a wide range of liver diseases including hepatocellular carcinoma (HCC). Because of the similar modes of transmission, HBV HCV co-infections are found in approximately 7–20 million people globally. Compared with HBV or HCV mono-infections, co-infections are associated with more severe liver diseases and higher risk of HCC. Abnormal lipid biosynthesis and metabolism has been increasingly recognized as a cause for cancer. While HBV infection does not seem to significantly increase the risk of developing hepatic steatosis, steatosis is a prominent feature of chronic hepatitis C (CHC). In addition, steatosis in HBV or HCV mono-infections is a significant and independent risk factor for HCC. However, whether and how HBV HCV co-infections synergistically increase the risk of HCC development through modulating lipid metabolism is not well understood. Possible mechanisms by which steatosis causes HCC include: activation of sterol regulatory element-binding protein-mediated lipogenesis through the PI3K–Akt pathway, abnormal activation of peroxisome proliferator-activated receptors and endoplasmic reticulum stress. Here, we review the potential mechanisms by which HBV HCV co-infections may increase HCC risk through modulation of lipogenic gene expression. We begin with reviewing the impact of HBV and HCV on host lipogenic gene expression and carcinogenesis. We then discuss the potential mechanisms by which HBV and HCV can increase carcinogenesis through synergistically activating lipid biosynthesis and metabolism. We end by sharing our thoughts on future research directions in this emerging paradigm with an ultimate goal of developing effective therapeutics.