Developing therapies to treat hepatitis C infection in post-liver transplant recipients

ABSTRACT

Introduction: Currently, hepatitis C virus (HCV) infection remains the most common indication for liver transplant in the United States (US) with almost universal HCV recurrence in the post-liver transplant setting. Previous interferon (IFN)-related efficacy and tolerability concerns about worsening liver function have limited treatment options for many patients with HCV-associated decompensated liver disease and post-liver transplant recipients. However, the last decade has seen a seen a radical shift in the management of HCV with multiple direct-acting antiviral (DAA) treatments that provide more effective, all-oral, IFN-free alternatives.

Areas covered: This review will serve to highlight the various pharmacotherapies available to clinicians for patients with HCV recurrence post-liver transplant. A brief history of prior regimens is provided with evidence for newer treatments presented. Also detailed are updated guidelines from societal organizations. Finally, timing of HCV treatment is discussed as the decision to treat patients in a pre or post-liver transplant setting remains challenging.

Expert opinion: While there are many potential available therapies for HCV recurrence in the post-liver transplant setting, daclatasvir/sofosbuvir and ledipasvir/sofosbuvir have been the most extensively studied. Newer, pangenotypic generation drugs require more evidence before routine utilization in post-liver transplant recipients.

KEYWORDS:

• Cirrhosis
• direct-acting antiviral (DAA) therapy
• hepatitis C virus (HCV)
• liver transplant

Article highlights

• Recurrence of hepatitis C virus (HCV) following liver transplant is almost universal in patients with ongoing viremia and is associated higher rates of allograft failure and death.

• Newer, direct acting antiviral (DAA) therapies have significantly improved HCV eradication rates, and extended treatment to many patients previously ineligible to receive interferon (IFN)-based regimens.

• At present, there is limited HCV treatment specific data for post-liver transplant patients with mild and advanced liver disease.

• There is sufficient evident to recommend daclatasvir/sofosbuvir and ledipasvir/sofosbuvir in combination with ribavirin as first line pharmacotherapies for HCV in post-liver transplant recipients.

• Further studies are needed specific to the post-liver transplant population before newer pangenotypic regimens can be adopted.

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Declaration of interest

JK. Lim reports research contracts (to the institution) from Bristol-Myers Squibb, Gilead, and Hologic; and has received consulting honoraria from Bristol-Myers Squibb and Gilead. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded.