Temporal treatment with interferon-β prevents hepatocellular carcinoma in hepatitis B virus X gene transgenic mice

Background/Aims The preventive effect of interferon (IFN) against hepatocellular carcinoma (HCC) has been confirmed clinically. We sought to determine whether the temporal administration of IFN-β prevents hepatocarcinogenesis in a mouse model where HCC develops without necroinflammation. Methods Hepatocarcinogenic mice that are transgenic for the hepatitis B virus X gene (HBx-Tg) were treated with IFN-β or saline (control) for three months, from 3 to 6 months of age, and the incidence of HCC was determined at 18 months of age. The effects of IFN-β on DNA synthesis and apoptosis were tested. Results The incidence of HCC was significantly lower in the IFN-β-treated mice than the controls (0 vs. 50%, P < 0.01). Inhibition of DNA synthesis in hepatocytes by IFN-β was observed in the livers of HBx-Tg, without any significant induction of apoptosis. Although the treatment of IFN-β was temporal, the number of hepatocytes with DNA synthesis remained lower 3 and 12 months later in life. Conclusions Temporal administration of IFN-β has a significant preventive effect on the occurrence of HCC in a mouse model where HCC develops without inflammation. The mechanisms are the inhibition of DNA synthesis and cell cycle progression of hepatocytes.