The clinical and immunologic impact of using interferon and ribavirin in the immunosuppressed host

Abstract

Key Points 1. Allograft infection with hepatitis C virus (HCV) in immunosuppressed adults results in decreased allograft and patient survival. 2. Risk factors for accelerated progression of hepatitis C related to immunosuppression include treated episodes of acute cellular rejection (ACR), pulse therapy with methylprednisolone, and use of OKT3. 3. Both interferon alfa (IFN-α) and ribavirin (RVN) show antiviral actions against HCV and stimulate innate and adaptive immunity to increase cytolysis and polarize T helper subtype 1 (TH1) responses. In addition, IFN-α inhibits fibrogenesis in the liver. 4. Both IFN-α and RVN have been studied in immuno-suppressed liver transplant recipients as prophylaxis or treatment of established hepatitis C to reduce allograft failure and patient mortality. Reported protocols include monotherapies with RVN, standard IFN-α, and pegylated IFN-α and combination therapies using RVN and either standard IFN-α or pegylated IFN-α. 5. The clinical impact of using IFN-α and RVN in highly selected immunosuppressed patients varied among studies. Combination therapy with standard IFN-α and RVN resulted in the greatest sustained biochemical and virological responses. However, no therapy prevented progression of acute cholestatic hepatitis C despite evidence of virological responses. Substantial proportions of patients developed adverse events requiring dose reduction or discontinuation that compromised efficacy. RVN monotherapy was not only virologically ineffective, but may have stimulated hepatic fibrosis. Current data regarding monotherapy or combination therapy with pegylated IFN-α are limited, but encouraging. 6. Despite potent immunostimulatory actions of both IFN-α and RVN that enhance natural killer, TH1, their use did not significantly increase the incidence of ACR. 7. Additional studies are needed to resolve the controversy over prophylaxis versus treatment of established disease and the potential utility of low-dose maintenance IFN-α therapy to retard fibrogenesis without clearing HCV. 8. After new, less toxic, and more potent antiviral agents become available, they should be tested immediately in patients with hepatitis C post-liver transplantation.