Effect of immunosuppressive and antiviral agents on hepatitis B virus replication in vitro

Hepatitis B virus (HBV) DNA-transfected hepatoma cells were incubated with the immunosuppressive agents prednisolone, azathioprine, and cyclosporin A (CsA) and the antiviral agents ganciclovir and foscarnet to investigate the effects of these compounds on HBV replication. Prednisolone and azathioprine increased intracellular viral DNA and RNA levels approximately twofold and fourfold, respectively. Treatment with CsA did not alter the levels of viral RNA or DNA. A combination of all three immunosuppressive agents increased the level of intracellular viral DNA eightfold, indicating an additive effect. Incubation of the cells in the presence of foscarnet decreased levels of both single-stranded and relaxed circular viral DNA, and in the presence of ganciclovir decreased the levels of relaxed circular viral DNA, predictable effects from their known mechanism of action. The stimulatory effect on viral replication induced by the combination of immunosuppressive agents was substantially inhibited by ganciclovir-foscarnet treatment. These observations could have implications for the management of recurrent HBV infection after liver transplantation.