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. (HEPATOLOGY 1995; 22:36-43.)
Orthotopic liver transplantation has become an important therapeutic option for patients with acute and chronic liver failure. However, in patients transplanted for end-stage liver disease caused by chronic hepatitis B, the high frequency of recurrent hepatitis B virus (HBV) infection is a major problem. Recurrent HBV infection may be associated with a dramatic increase in viral replication compared with the pretransplantation state; this may be followed by the rapid development of severe and progressive graft damage.' The factors that lead to severe posttransplantation recurrence of hepatitis B are not well understood. However, it has Abbreviations: HBV, hepatitis B virus; CsA, cyclosporin A HBsAg, hepatitis B surface antigen; HBeAg, hepatitis I3 e antigen; RC, relaxed circular; SS, single-stranded; WHV, woodchuck hepatitis virus.