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The clinical and immunologic impact of using interferon and ribavirin in the immunosuppressed host
Author(s) -
Braun Marius,
Vierling John M.
Publication year - 2003
Publication title -
liver transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.814
H-Index - 150
eISSN - 1527-6473
pISSN - 1527-6465
DOI - 10.1053/jlts.2003.50257
Subject(s) - medicine , ribavirin , immunosuppression , hepatitis c virus , pegylated interferon , hepatitis c , immunology , alpha interferon , gastroenterology , interferon , virus
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 (T H 1) responses. In addition, IFN‐α inhibits fibrogenesis in the liver. 4. Both IFN‐α and RVN have been studied in immunosuppressed 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, T H 1, 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.