Clearance of Hepatitis C Virus following Immune Checkpoint 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 hepatitis 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 PD-1/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 40 s identified by a re-engagement initiative for HCV, who had been unaware of his diagnosis. On further investigation he was found to have compensated for liver cirrhosis and HCC. He was treated with HCV 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 antiviral T-cell exhaustion. This would therefore support further investigation into other chronic viral infections that create tumour associated with immunosuppressive microenvironments.