Hepatitis C therapy before and after liver transplantation.
1. Pretransplant therapy, using a low-accelerating-dose regimen, is an option for patients with mildly decompensated liver disease and low laboratory Model for End-Stage Liver Disease scores. Achievement of an on-treatment virologic response is the goal of therapy. Preliminary data suggest that up to two-thirds of patients who become hepatitis C virus RNA-negative on treatment will be hepatitis C virus infection-free post-transplantation. 2. Effective prophylactic therapies are not available. Hepatitis C antibody therapy has been ineffective in preventing hepatitis C virus infection in studies to date. 3. Preemptive antiviral therapy started within weeks of transplantation is limited by tolerability, particularly in patients with high Model for End-Stage Liver Disease scores pre-transplantation. Rates of sustained virologic response vary from 8% to 39%. Histological benefits in virologic nonresponders have been demonstrated. 4. Posttransplant antiviral therapy in those with evidence of recurrent disease is the mainstay of management. A combination of pegylated interferon and ribavirin is the treatment of choice, and sustained virologic response is achieved with 48 weeks of treatment in approximately 30% of treated patients. Attainment of early loss of hepatitis C virus RNA is highly predictive of sustained virologic response. Histologic improvements are seen in responders. Survival is prolonged among those achieving a sustained virologic response. 5. Posttransplant antiviral therapy is limited by poor tolerability and the frequent need for dose reductions and/or discontinuation. Immunologic complications, including acute rejection, chronic rejection, and autoimmune-like hepatitis, occur in association with therapy, albeit at low rates. 6. Hepatitis C virus-infected liver transplant recipients represent an important patient population in need of new therapeutics options to prevent patient and graft losses due to recurrent hepatitis C virus disease.
Terrault
Norah A
NA
Division of Gastroenterology, Department of Medicine, University of California-San Francisco, San Francisco, CA 94143, USA. norah.terrault@ucsf.edu
D000998:Antiviral Agents / Q000627:therapeutic use*; D006526:Hepatitis C / Q000188:drug therapy* / Q000517:prevention & control / Q000601:surgery; D006801:Humans; D016031:Liver Transplantation; D055502:Secondary Prevention
D000998:Antiviral Agents