Effects of immunosuppressive therapy on hepatic expression of hepatitis B viral genome and gene products.

To determine the effect of immunosuppressive therapy on hepatic expression of hepatitis B virus (HBV) DNA and antigens in vivo, serial biopsies from 12 patients with chronic active hepatitis B who had been given immunosuppressive therapy (prednisolone 10-15 mg +/- azathioprine 75-125 mg daily) in an earlier period were studied using immunohistochemistry and non-isotopic in situ hybridization. Four out of the 12 patients were positive for hepatic HBcAg/HBeAg/HBV DNA before immunosuppressive therapy. In these 4 patients positive for HBcAg, there was an increase in staining intensity and the proportion of liver cells positive for both HBcAg/HBeAg/HBV DNA and HBsAg during therapy. Of the 8 patients negative for hepatic HBcAg/HBeAg/HBV DNA before immunosuppressive therapy, hepatic HBcAg, HBeAg, and HBV DNA were detected in 2 patients, along with stronger and more diffuse hepatic expression of HBsAg. The other 6 patients also had an increase in hepatic HBsAg expression but without HBcAg. These data provide in vivo evidence that in some patients, immunosuppressive therapy enhances hepatic expression of both HBV genome and gene products.