Therapeutic management of recurrent hepatitis C after liver transplantation

Abstract

Recurrent hepatitis C ranges from minimal damage to cirrhosis developing in a few months or years in a substantial proportion of transplant recipients. Different virus, host and donor factors are involved in the pathogenesis of recurrence, but many are poorly understood. Therapeutic strategies can be utilized in the pre-, peri-or posttransplantation setting. Antiviral therapy using interferon and ribavirin and modifying immunosuppression are the main strategies to prevent progression disease. The efficacy of interferon and ribavirin is limited and side effects, reduction/withdrawal are frequent. Current sustained virological response rates are approximately 28%. An optimal immunosupppression regimen has not been established. The choice of calcineurin inhibitors has not clearly been shown to affect histological hepatitis C virus (HCV) but higher cumulative exposure to corticosteroids to treat acute rejection is associated with more severe recurrence. The manner in which the doses of immunosuppression are modified has more influence on HCV recurrence than the use of a specific drug per se. Debate about the influence of immunosuppressive regimens on HCV recurrence is ongoing. Potential antifibrotic therapy and new agents targeting HCV infection and replication are emerging and are anticipated to be added to our armentarium in battling recurrent HCV post-LT.

Hepatitis C virus infection in haemodialysis and kidney transplant patients

“…The intensity of the induction and maintenance immunosuppressive regimen may have a significant impact on the course of HCV infection after transplantation. For example, corticosteroids and T-cell depleting antibody therapy have been associated with enhanced viral replication and rapid progression to cirrhosis after liver transplantation [102]. Conflicting data exist on the effect of other immunosuppressive drugs such as calcineurin inhibitors, mTOR inhibitors, mycophenolate mofetil and anti-IL2-receptor monoclonal antibodies on HCV reactivation.…”

Hepatitis C virus entry: possible targets for therapy

“…HCV infects the allograft in the majority of cases, often resulting in a more rapid and aggressive disease progression that is less responsive to interferon and ribavirin therapy (reviewed in Teixeira et al 123). Viral attachment and internalisation are crucial to initiating infection in the allograft, and therapeutic intervention of these early steps in the life cycle may reduce HCV infection rates.…”

Telaprevir versus simeprevir for the treatment of recurrent hepatitis C after living donor liver transplantation

“…Pegylated interferon (PEG IFN) with ribavirin (RBV) has long been the only treatment option for managing HCV in LT and non‐LT settings . In post‐LT settings, however, the outcomes of PEG IFN/RBV therapy are often poor because only one‐third of patients treated with PEG IFN/RBV had a sustained viral response (SVR) …”