Published online Mar 14, 2018. doi: 10.3748/wjg.v24.i10.1084
Peer-review started: January 11, 2018
First decision: January 25, 2018
Revised: January 31, 2018
Accepted: February 9, 2018
Article in press: February 9, 2018
Published online: March 14, 2018
Core tip: With the development of hepatitis B virus (HBV) vaccine, the rate of chronic HBV infection has dramatically declined worldwide. However, the incidence of hepatocellular carcinoma (HCC), which is characterized by poor prognosis and low survival rate, is on the rise. Predominance in males is a representative global epidemiological characteristic of HCC. Recently, we introduced the novel W4P substitution into the preS1 region, which associated with HCC and notably occurred exclusively in male patients. Our study in the nude mouse xenograft model indicated that the W4P mutation likely contributed to IL-6-dependent HCC progression, particularly in male individuals. Here, to gain further insight into the role of this mutation in HBV-induced liver inflammation, we created transgenic mice carrying the full HBV genome with this mutation. Of note, our data showed that W4P transgene males of 10 mo of age, but not W4P transgene females, spontaneously developed liver damage due to IL-6-mediated liver inflammation, further supporting the previous finding regarding the contribution of the W4P mutation to sex disparity in susceptibility to HCC. Furthermore, our results prove the utility of the developed W4P transgene mouse model for research into the mechanisms of HBV-caused liver diseases.