Chapter 16: Treatment of Hepatitis C before and after Transplantation

INTRODUCTION

Hepatitis C is the most common cause of chronic hepatitis C in the United States, affecting an estimated 2.4 million people, most of whom have not yet been identified.¹ Cirrhosis as a result of hepatitis C infection is a common indication for liver transplantation and is a major predisposing factor for the development of primary hepatocellular carcinoma in the United States.^2,3 Risk factors for progression to cirrhosis in hepatitis C infection include male sex, age greater than 50 years, alcohol use, the presence of nonalcoholic fatty liver disease, hepatitis B virus (HBV) and HIV co-infection, and immunosuppressive therapy.^4,5

Treatment options for chronic hepatitis C have advanced rapidly since the virus was first identified in the early 1990s. Initial treatment for hepatitis C included interferon given subcutaneously with or without ribavirin. These therapies were associated with low sustained viral response rates (SVRs) and significant side effects. In 2013, first-generation protease inhibitors were approved by the Food and Drug Administration (FDA) in combination with pegylated interferon and ribavirin. These therapies had limited use due to significant toxicities. Starting in 2014, new direct-acting combination antiviral therapies were introduced to the marketplace, which are well tolerated with minimal adverse events associated with them and with SVRs of greater than 90% in all patient groups, including all genotypes and patients with cirrhosis.⁶

Hepatitis C is an approximate 10,000-base-pair RNA virus. Treatment advances have focused on the development of direct-acting antiviral therapies, which specifically inhibit hepatitis C viral replication at the NS3, NSa, NS5A, and NS5B regions. Since 2014, tremendous advances have been made in the treatment of chronic hepatitis C infection with the introduction of NS3-4A protease inhibitors, NS5A inhibitors, and nucleoside and non-nucleoside NS5B polymerase inhibitors for use in the treatment of chronic hepatitis C before and after liver transplantation in genotypes 1 to 6.

TREATMENT OF CHRONIC HEPATITIS C INFECTION

Treatment of chronic hepatitis C infection is dependent upon multiple factors, including genotype, the presence or absence of cirrhosis, the presence of decompensated cirrhosis, the presence of hepatocellular carcinoma, and the presence of resistance-associated substitutions (RAS) [genotype 3 only]. No dose adjustment is recommended when using currently available direct-acting antiviral therapies. Most currently widely used therapies are pan-genotypic. All therapies are oral.

Therapy with glecaprevir/pibrentasvir is 3 tablets daily. Therapy with ledipasvir/sofosbuvir, sofosbuvir/velpatasvir, and sofosbuvir/velpatasvir/voxilaprevir is 1 pill ...