Conclusions
HCV cirrhosis remains the leading indication for LT and this demand is projected to double in the next decade. Unfortunately, HCV infection of the allograft is universal and associated with accelerated disease progression with reduced graft and patient survival compared to other transplant indications.
Current antiviral therapy, with a PEG-IFN/RBV component, has limited applicability peri- and post-LT because of poor tolerability and efficacy in these patient populations. The improved efficacy of first-generation PIs, boceprevir and telaprevir, in the treatment of recurrent hepatitis C is offset by increased toxicity in LT recipients, especially anemia, and significant drug–drug interactions, especially with tacrolimus.
In contrast, the NUC-NS5B inhibitors and the NS5A inhibitors lack toxicity and significant drug interactions with either cyclosporine or tacrolimus and seem ideally suited for post-LT treatment of recurrent HCV infection. Recent clinical studies of SOF plus RBV therapy confirm the safety and efficacy of IFN-free DAA therapy before and after LT. Subsequent studies of DAA combinations (SOF plus ledipasvir, or ABT-450/ABT-333/BT-267) are expected to achieve almost 100% response with shorter duration of therapy.
In summary, chronic hepatitis C is both the leading indication for LT and the leading cause of posttransplant graft loss. The poor tolerability of IFN-based therapy in decompensated liver disease has limited pretransplant treatment to well-compensated patients listed for HCC. The primary goal of IFN-based antiviral therapy was to improve posttransplant outcomes through delayed treatment of patients with established recurrence in the allograft. The superior efficacy and tolerability of direct antiviral agents should move the primary goal of antiviral therapy to universal pre-LT prophylaxis in all patients listed with HCV cirrhosis, thus abrogating the impact of HCV allograft infection and improving long-term graft and patient survival. Finally, combination DAA therapy may salvage patients presenting with decompensated HCV cirrhosis, thereby reducing both the demand for LT and the need for re-LT.