Supplementary Material for: Clearance of hepatitis C virus following immunecheckpoint inhibitor therapy for hepatocellular carcinoma: Case Report

Introduction Patients with advanced hepatocellular carcinoma (HCC) have limited treatment options in the context of decompensated cirrhosis. HCC occurs in patients with hepatis C virus (HCV) infection and cirrhosis at 1-4% per year. Direct-acting antiviral (DAA) efficacy is decreased in the presence of HCC. We present a case where immunotherapy may have resulted in HCV clearance, when DAA therapy had been ineffective. We hypothesise that immune checkpoint inhibitors targeting the PD1/PD-L1 pathway can reverse T cell exhaustion and aid in the clearance of chronic HCV. Case presentation This case study describes a male in his 40s identified by a re-engagement initiative for hepatitis C virus (HCV), who had been unaware of his diagnosis. On further investigation he was found to have compensated liver cirrhosis and hepatocellular carcinoma (HCC). He was treated with HCV direct acting antiviral (DAA) therapy (Sofosbuvir/Velpatasvir) and then systemic immunotherapy for HCC with Atezolizumab and Bevacizumab, in an attempt to downstage the disease. Hepatitis C therapy did not achieve sustained virological response, with viral relapse after the end of treatment. This, combined with ongoing alcohol use, resulted in hepatic decompensation and cessation of immunotherapy after the fifth cycle. The HCV RNA subsequently became undetectable without further DAA re-treatment. Conclusion To our knowledge, this is the first case of HCV clearance after DAA relapse and the timing of this event after immunotherapy suggests a causal link. We hypothesise that this may be due to the reversal of anti-viral T cell exhaustion. This would therefore support further investigation in other chronic viral infections that create tumour associated immunosuppressive microenvironments.