Management of Recurrent Hepatitis C Following Liver Transplantation: Predictors of Sustained Viral Clearance

Achievement of SVR in the setting of recurrent HCV following liver transplantation may have a major impact on long-term outcomes, including improved graft and patient survival. Identifying patients with a greater likelihood of achieving SVR is an important consider­ation in the selection of potential treatment candidates and is a key factor in developing strategies for optimizing response to therapy. HCV genotype remains an impor­tant predictor of SVR in the post-transplant setting, as sustained clearance may be significantly higher in non- genotype 1 patients, with reported SVR rates greater than 60%, particularly in patients with HCV genotype 2 or 3 infection. The most important predictor of success­ful response during a course of antiviral therapy before transplant is the serum HCV RNA level, with achieve­ment of rapid virologic response (RVR) at week 4 and early virologic response (EVR) at week 12 providing the highest positive and negative predictive values of SVR, respectively. In the post-transplant setting, rapid HCV clearance during therapy is also a key predictor of sustained response, as demonstrated in several pro­spective studies, including the PROTECT study, in which the greatest response was observed in those who cleared HCV within 4 weeks (RVR), followed by those who achieved viral clearance within 12 weeks (complete EVR).

Tolerance and Safety

A major limitation of both preemptive therapy and treatment of established HCV recurrence is tolerability, particularly with respect to the hematologic side effects of PegIFN and RBV. An additional factor that must also be addressed in this population is renal dysfunction and the potential for RBV toxicity. As with patients undergoing antiviral therapy in the nontransplant setting, adher­ence to both PegIFN and RBV based upon the adminis­tered dose and duration of therapy appears to have a major impact on the ability to achieve viral clearance in patients who have undergone liver transplantation. Thus, poor tolerance may contribute significantly to the lower overall SVR observed in the setting of recurrent HCV. The use of growth factors to minimize the potential for hematologic side effects associated with PegIFN and RBV (such as ane­mia and neutropenia) may have a particularly important role in this population. Although IFN-based therapy has been associated with an increased risk of kidney allograft rejection in kidney transplant recipients, prospective studies in liver transplant recipients have not reported an increased risk of liver allograft rejection. The ability to optimize adherence to both therapy and viral clearance will continue to be an important consideration in the development of strategies utilizing IFN-based regimens in patients with recurrent HCV.
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