The driving circuit of HBx and androgen receptor in HBV-related hepatocarcinogenesis

Hepatocellular carcinoma (HCC) is a global health concern. The sixth most common neoplasm, HCC yields a poor prognosis and high mortality rate, causing approximately 500 000 deaths per year. Chronic viral hepatitis—especially HBV and HCV—are major aetiologies of HCC, accounting for approximately 80% of HCC cases, particularly in endemic areas. Another clinical feature of HCC is that it disproportionately occurs in men, and the ratio of male to female patients ranges from 2 to 7:1.1 In large cohort studies, this predominance is only partly explained by gendered differences in environmental influences and behaviours, for example, carcinogen exposure and alcohol consumption; this implies that host genetic factors are crucial determinants. One Taiwanese study revealed that higher serum androgen levels and more active androgen receptor (AR) alleles were associated with an increased risk of HCC among male carriers of HBV, but not men infected with HCV.2 The animal study supported the importance of androgen and AR signalling pathway in determining the male predominance in a chemically induced HCC mouse model.3 These studies have emphasised the carcinogenic effect exerted by the male sex hormone pathway in HBV-related HCC. Among men, androgen is primarily produced in the testes and circulates in body serum, eventually being converted to potent dihydrotestosterone by 5α-reductase within target cells. The biological functions of androgen are elicited when it binds …