Antiviral therapy for hepatitis C in the setting of liver transplantation.

Hepatitis C viremia after liver transplantation for hepatitis C virus (HCV) liver disease is universal. Progressive HCV disease after transplantation is the leading cause of death, graft failure, and retransplantation. Whether to treat, with which agents, and timing of therapy are unanswered questions. Timing options include pretransplantation, prophylactic, post-transplantation preemptive, and post-transplantation recurrence-based therapy. The latter is most commonly utilized. There are little data for each of these, much less comparisons. Pegylated interferon-alpha has supplanted standard interferon-alpha due to increased efficacy and is generally used in combination with ribavirin (RBV). Efficacy is less than in nontransplant settings due to immunosuppression, an increased prevalence of genotype 1 HCV, patient comorbidities, and decreased functional status. Administration of HCV therapy to cirrhotic patients prior to transplantation may eradicate or suppress HCV and prevent or reduce severity of recurrence. Sustained virological response (SVR) as high as 50% was attained in genotypes 2 or 3 HCV. Comparison of preemptive and histology-based post-transplantation HCV therapy should be done, and more data will be available on pretransplantation therapy. Post-transplant patients are less tolerant of therapy, particularly RBV. SVR, the primary goal of therapy, likely halts disease progression, but only 20% to 30% of treated patients achieve SVR. Preemptive therapy early after transplantation may have advantages due to the potential to delay or blunt severity of graft infection and recurrent hepatitis. In post-transplant therapy, RBV toxicity is attenuated in relation to decreased renal function, and side effects of interferon are more prominent. An ongoing trial will assess preemptive therapy with treatment after histologic recurrence. Novel anti-HCV therapies such as protease and polymerase inhibitors are emerging. These must be tested with urgency in the transplant setting. Retransplantation for progressive HCV disease is more controversial due to poor outcomes, graft shortage, and disease recurrence.