Figure 1.

Illustration of the positive feedback loop between HBx and AR for promotion of HBV-induced hepatocarcinogenesis in male CHB patients. In male HBV carriers with chronic infection, HBx enhances the transcriptional activity of androgen-activated AR, which recognizes the androgen-responsive element (ARE) motifs within viral enhancer I (Enh I), thus reinforcing overall HBV gene expression including HBx (the right part). On the other hand, the HBx-activated AR could aberrantly stimulate downstream expression of proto-oncogenes, which facilitate cell proliferation and survival in the carcinogenic process. This positive feedback circuitry may simultaneously elevate serum HBV titer and activate host genes with carcinogenic potentials in infected hepatocytes, leading to the elevated risk of HCC development in male CHB patients.