INFO: Management of Hepatitis C in Liver Transplant Recipients Posted 02/28/2006

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Management of Hepatitis C in Liver Transplant Recipients Posted 02/28/2006 Medscape Abstract and Introduction Abstract Recurrent hepatitis C virus (HCV) disease is the leading cause of graft loss in liver transplant recipients with pre-transplant HCV infection. While natural history is variable, median time to recurrent cirrhosis is less than a

decade. Factors contributing to risk of recurrence and rate of fibrosis progression are only partially known. Older donor age, treatment of acute rejection, cytomegalovirus infection and high pre-transplant viral load are most consistently linked with worse outcomes. Whether these factors can be modified to positively impact on HCV disease progression is unknown. The main therapeutic approach for patients with recurrent HCV disease has been the treatment with interferon and ribavirin (RBV) once recurrent disease is documented or progressive. Efficacy is lower than in nontransplant patients and tolerability, especially of RBV, is a major limitation. Stable or improved fibrosis scores are seen in the majority of sustained responders. Optimal dose, duration and timing of treatment have not been determined. Alternative strategies under study include pre-transplant treatment of decompensated cirrhotics, preemptive antiviral therapy started within weeks of transplantation and

prophylactic therapy using HCV antibodies. Ongoing studies may establish a future role for alternative treatment approaches. Additionally, limited overall efficacy of interferon-based therapy in the transplant setting highlights the urgent need for new drug therapies. Introduction End-stage liver disease caused by chronic hepatitis C virus (HCV) infection is the most common indication for liver transplantation in the United States and Western Europe. Following liver transplantation, graft reinfection with HCV is essentially universal and the rate of fibrosis progression is accelerated as compared to immunocompetent patients with HCV. Recurrent disease affects long-term graft survival. Patients with HCV-related liver disease have a 23% increased rate of mortality and a 30% increased rate of graft loss at 5 years post-transplantation as compared to patients transplanted for other indications.[1] Cirrhosis is reported in up to

30% of recipients within 5 years,[2] and progression is not linear.[3] Once cirrhosis is established, patients are at high risk for complications, with up to 42% developing liver decompensation within 1 year.[4] Retransplantation, the only definitive therapy for recurrent disease with decompensation, is controversial in patients with HCV, as their survival is inferior compared to patients with non-HCV indications.[5,6] Given the limited availability of donor organs and the tremendous resources invested into each liver transplant recipient, strategies to maintain the long-term survival of HCV-infected patients are of paramount importance. An improved understanding of the host, viral and external factors influencing HCV disease recurrence is essential, as some factors may be modifiable. Therapeutic interventions undertaken prior to or after transplantation represent an important means of preventing

infection or modify the risk of progressive HCV disease. Section 1 of 4 Next Page: Factors Influencing the Natural History of Recurrent HCV Disease Section 2 of 4 Next Page: Prevention and Treatment of Recurrent HCV Disease Section 3 of 4 Next Page: Summary and Future Directions Section 4 of 4 Management of Hepatitis C in Liver Transplant Recipientshttp://www.medscape.com/viewarticle/523521