Direct modulation of HBV surface antigen in a human, HBsAg-producing hepatocellular carcinoma cell line by alpha,...

A transient depression of HBV serologic markers has been reported for some chronically infected patients treated with human interferons. To determine a molecular basis for these observations, a human, HBV-carrying, hepatocellular carcinoma cell line (PLC/PRF/5) was treated with human alpha, beta, or gamma interferons. Administration of these interferons resulted in a marked depression of HBV surface antigen (HG-sAg) levels in the culture medium. This inhibition was transient, with media levels of HBsAg rising substantially within 48 hours following the termination of interferon treatment. Cell growth rates were not affected by alpha interferon treatment, indicating that overall cell protein synthesis was not substantially altered. Although all three classes of interferons were effective in lowering HBsAg levels in the culture medium, intracellular levels of HBsAg-specific RNA were unaffected. These results suggest that the transient depression of HBV serologic markers in interferon-treated patients may be a consequence of the failure to disrupt the intracellular pools of HBV RNA in the liver.