Management of hepatitis C infection before and after liver transplantation

Abstract

Chronic hepatitis C (CHC) is the most common indication for liver transplantation (LT). Aggressive treatment of hepatitis C virus (HCV) infection before cirrhosis development or decompensation may reduce LT need and risk of HCV recurrence post-LT. Factors associated with increased HCV risk or severity of recurrence include older age, immunosuppression, HCV genotype 1 and high viral load at LT. HCV recurrence post-LT leads to accelerated liver disease and cirrhosis development with reduced graft and patient survival. Currently, interferon (IFN)-based regimens can be used in dual-agent regimens with ribavirin, in triple-agent antiviral strategies with direct-acting antivirals (e.g., protease inhibitors telaprevir or boceprevir), or before transplant in compensated patients to reduce HCV viral load to prevent or reduce the risk of post-LT recurrence and complications; they cannot be used in patients with decompensated cirrhosis. IFN-based regimens are used in less than half of HCV-infected patients waiting for LT due to extremely low efficacy and poor tolerability. However, antiviral therapy is indicated after LT in patients with histologically confirmed CHC despite tolerability issues. Improvements in side effect management have increased survival in patients achieving therapeutic targets. HCV treatment pre- and post-LT results in significant health care costs especially when lack of efficacy leads to disease worsening, although studies have shown sofosbuvir treatment before LT vs conventional post-LT dual antiviral is cost effective. The suboptimal efficacy and tolerability of IFN-based therapies, plus the significant economic burden, means the need for effective and well tolerated IFN-free anti-HCV therapy for pre- and post-LT remains high.

Keywords: Hepatitis C virus, Orthotopic liver transplantation, Interferon-free treatment, Decompensated cirrhosis, Chronic hepatitis C

Core tip: This paper discusses alternative treatment options for patients with hepatitis C virus (HCV) undergoing liver transplantation (LT), particularly those with decompensated cirrhosis in whom interferon (IFN)-based therapy is contraindicated. Virtually all patients undergoing LT experience HCV recurrence leading to accelerated liver disease and cirrhosis development with reduced graft and patient survival. Novel IFN-free antiviral therapies featuring better efficacy and tolerability in such patients shall increase sustained virologic response rates while decreasing side effects and drug interactions, thus preventing progression of HCV-related liver disease, decreasing the general costs associated with both HCV treatment and worsening of patient health.