Impact of Direct Acting Antivirals on Survival in Patients with Chronic Hepatitis C and Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) represents a global public health burden, affecting an estimated 14 million persons worldwide, and is the third leading cause of cancer mortality. Within the United States, HCC is ranked 7th for cancer related mortality and has seen a doubling in incidence from 1975 to 2007. The primary predisposing factors for HCC carcinogenesis is liver cirrhosis. Cirrhosis risk factors include chronic alcohol use, viral hepatitis, including hepatitis c (HCV), and non-alcoholic fatty liver disease. Chronic HCV infection is the second most common risk factor for HCC and is responsible for 10–25% of all HCC cases. Over 20–30 years, 20–30% of patients with chronic HCV infections will develop cirrhosis and end stage liver disease and 1–4% of these patients will progress to HCC each year. Of all HCV related HCC cases, 80–90% occur in the setting of cirrhosis. With more than 3.5 million HCC patients in the United States and an estimated 130–170 million patients worldwide currently infected with HCV, the importance of HCV management in HCC therapeutic care and prevention is clear. The major current therapeutic goal for HCV and prevention of liver disease progression is sustained viral response (SVR), which is defined by negative HCV RNA at 12 weeks post-treatment (SVR12) and appears to be durable with a late virologic relapse rate of less than 1%. Therapeutic management of HCV has recently shifted from interferon-based therapies to all-oral interferon-free direct-acting antiviral (DAA) combination regimens. DAAs are a new class of drugs that target nonstructural proteins responsible for replication and infection of the hepatitis c virus. Genotype specific DAA therapies have been shown to reach SVR12 exceeding 90% of patients with fewer adverse effects compared with historic interferon-based regiments. SVR12 from DAA regimens have been associated with a decrease in liver outcomes including cirrhosis, hepatic decompensation, HCC and mortality. However, the impact of DAA regimens on clinical outcomes in patients with HCC remain limited. This study evaluates the impact of DAA on overall survival in HCV patients with HCC with the a priori hypothesis that SVR12 would be associated with improved outcome.