• HCV;
  • IFN;
  • immune evasion;
  • innate response;
  • liver;
  • quasispecies;
  • recurrence;
  • T cell;
  • transplantation;
  • viral evolution

Hepatitis C virus (HCV) infection is a major global health problem affecting 170 million people worldwide. The majority of infected individuals fail to resolve their infection, with a significant number developing chronic, progressive HCV-related liver disease. HCV infection is the leading indication for liver transplantation and unfortunately, all patients with detectable viral load before transplantation will have rapid, recurrent infection. What remain to be determined are factors contributing to the severity of HCV recurrence. Such factors are unique to the posttransplant setting and include: viral genetic diversity and composition, immunosuppression, donor/recipient age and sex, genetic factors and the liver microenvironment. Importantly, the possibility that the severity of HCV recurrence might be also influenced by factors related to the primary course of disease (i.e. viral set point, previously acquired adaptations of the virus) must be further evaluated. In this sense, recurrent HCV infection should not be regarded merely as another acute infection, but rather, it should be cautioned that problems first arising during the primary course of disease may be accentuated during recurrence. Development of novel therapeutic approaches will require a thorough understanding of viral and host determinants of infection resolution and how these factors may change in the posttransplant setting.