Hepatitis C virus and liver transplantation: where do we stand?

Abstract

SummaryThe hepatitis C virus (HCV) infects more than 180 million people globally, with increasing incidence, especially in developing countries. HCV infection frequently progresses to liver cirrhosis leading to liver transplantation or death, and HCV recurrence still constitutes a major challenge for the transplant team. Antiviral therapy is the only available instrument to slow down this process, although its actual impact on liver histology, in responders and nonresponders, is still controversial. We are now facing a "new era" of direct antiviral agents that is already changing the approach to HCV burden both in the pre-and in the post-liver transplantation settings. Available data on sofosbuvir/ledipasvir and sofosbuvir/ simeprevir in patients with decompensated cirrhosis sustain a SVR12 of 89% [1], but one-third of patients do not clinically improved. The sofosbuvir/ribavirin treatment in stable cirrhotic patients with HCC before liver transplantation is associated with 2% recurrence rate if liver transplantation is performed at least one month after undetectable HCV-RNA is achieved. The treatment of recurrence with the new antiviral drugs is associated with a SVR that ranges between 60 and 90%. In this review, we have focused on the evolution of antiviral therapy for HCV recurrence from the "old" interferon-based therapy to the "new" interferon-free regimens, highlighting useful information to aid the transplant hepatologist in the clinical practice.

Dropout rate from the liver transplant waiting list because of hepatocellular carcinoma progression in hepatitis C virus–infected patients treated with direct‐acting antivirals

“…Median (range) post-LT FU was 9 (6-13) months and 11 (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) months for DAA-treated patients and controls, respectively.…”

“…(3) The new era of direct-acting antiviral (DAA) agents has already changed the management approach to HCV infection in the transplant setting. (4,5) It is…”

Current challenges and future directions for liver transplantation

“…more effective treatment options in HCV genotype 3, drug-drug interactions), new DAAs against HCV permit to cure more than 90% of HCV positive liver transplanted patients. [36][37][38][39] Thus, when transmitted during LT from HCVD+, recurrent hepatitis could be easily cured, contributing to the further expansion of the use of HCVD+.…”

Quasispecies of Hepatitis C Virus Participate in Cell-Specific Infectivity

“…In addition, many antiviral agents targeting non-structural proteins and host factors involved in HCV replication have been applied in a clinical setting2. On the other hand, re-infection of HCV in drug abusers or recipients of transplanted liver grafts remains a serious problem34.…”

“…The major differences between primary infection and re-infection of a transplanted liver are as follows: 1) HCV quasispecies escaping from the immune response are already present in the serum at liver transplantation; 2) extra-hepatic HCV can serve as a reservoir for infection of the graft; and 3) the recipients must undergo immunosuppression after liver transplantation3. Several reports have demonstrated that quasispecies were dynamically changed immediately after liver transplantation56.…”