Recurrence of hepatitis C after liver transplantation

Recurrence of hepatitis C virus (HCV) infection following liver transplantation is a major source of morbidity and mortality. The natural history of hepatitis C in the transplant setting is shortened. Overall, one third of HCV-infected recipients have developed allograft cirrhosis due to HCV recurrence by the 5^th-7^th year post-transplantation. The most significant variables which determine disease progression are the use of organs from old donors, the use of an inadequate immunosuppression (too low, inducing treatment rejection episodes, too potent or too rapidly changing), and the presence of comorbid conditions that also impact the quality of the graft (biliary complications, metabolic syndrome). The only factor consistently shown to modify the natural history of recurrent disease is antiviral therapy. A sustained viral response, achieved by one third of those treated with dual therapy, is associated with improved histology, reduced liver-related complications and increased survival. Variables associated with enhanced viral response with dual therapy include an adequate genetic background (IL28B C/C of both donor and recipient), good treatment adherence (full doses of ribavirin, treatment duration), lack of graft cirrhosis at baseline, and viral genotype non-1. Data with triple therapy are encouraging. Response rates of about 60% at end-of-therapy have been described. Drug-drug interactions with calcineurin inhibitors are present but easily manageable with strict trough levels monitoring. Side effects are frequent and severe, particularly anemia, infections and acute renal insufficiency. In the future new oral antivirals will likely prevent viral reinfection. In this review, we will cover the most significant but also controversial aspects regarding recurrent HCV infection, including the natural history, retransplantation, antiviral therapy, and outcome in HIV-HCV patients.