Direct-Acting Antiviral Therapy and Hepatocellular Carcinoma in Captive Chimpanzees With Long-Standing Chronic...

Chimpanzees are the only non-human species susceptible to hepatitis C virus (HCV) infection and have served as models in HCV pathogenesis and antiviral drug development. Despite this, the long-term clinical consequences of chronic infection and therapeutic efficacy of direct-acting antivirals (DAAs) in this species are poorly documented. We evaluated the virologic, biochemical, and clinical outcomes of DAA therapy in eight captive chimpanzees with experimental HCV infection, with a median infection duration of 36 years (range, 25-43). Seven individuals received glecaprevir/pibrentasvir (GLE/PIB) and one individual received sequential sofosbuvir/velpatasvir/ribavirin followed by GLE/PIB. Six individuals achieved sustained virologic response (SVR), however, hepatocellular carcinoma (HCC) was detected in three of the six SVR achievers, one in the absence of histological cirrhosis. Two chimpanzees experienced virologic failure: one developed NS5A-P32del following daclatasvir/asunaprevir exposure and relapsed despite sequential regimens, and another harbored dual NS5A mutations (L31F/Y93H) with persistent high-level viremia. These findings demonstrate that DAAs effectively eradicate long-standing HCV infection in chimpanzees, paralleling therapeutic outcomes observed in humans. Cases in this study also show that HCV-infected chimpanzees, like humans, are susceptible to HCC in the late stages of chronic infection. We recommend lifelong HCC surveillance for all HCV-exposed chimpanzees.