Sustained Virological Response of Hepatitis C with Immunotherapy for Hepatocellular Carcinoma: a case report

Introduction: Hepatitis C Virus (HCV) is a blood borne virus that will progress to a chronic state in 55-85% of cases. Though direct acting antivirals (DAA) offers an effective cure, HCV remains underdiagnosed and the development of complications of cirrhosis including HCC may be the only clinical clue prompting diagnosis. Achieving sustained virological response (SVR) with direct acting antivirals (DAA) is a therapeutic imperative even in advanced HCC to prevent decompensation and to reduce tumor recurrence. However, drug interactions, suboptimal response in HCC, and risk of provoking decompensation in cirrhosis are important considerations in initiating treatment. We present the novel case of SVR with immune checkpoint inhibitor (ICI) therapy in a treatment naïve host. Case: Mr. M is a 53-year-old male with alcohol use disorder, and remote intravenous drug use, presented with severe abdominal pain, acute anemia (hemoglobin 7.6g/dL), hypotension (systolic BP 94mmHg). CT imaging revealed cirrhotic morphology and an 8cm liver lesion with tumor thrombosis and hemoperitoneum consistent tumor rupture. His Childs Pugh Score was B-9. AFP was 1972ng/mL. Liver biopsy confirmed mixed biphenotypic HCC/Cholangiocarcinoma. Etiological screen returned positive for HCV (antibody positive, RNA 20,500 IU/mL, genotype I). Treatment was deferred due to ‘advanced malignancy’. He started systemic therapy as tremelimumab and durvalumab, achieving significant tumor response. His HCV titer climbed to 895,000 IU/mL 5 months after starting treatment before declining and remaining persistently undetectable even after completion of immunotherapy. Subsequent disease progression was managed with TACE and SBRT. Systemic therapy was complicated by grade II ICI-hepatitis responsive to prednisone. Discussion: This case shows immune checkpoint inhibition can reverse immune tolerance of chronic HCV and can achieve SVR without DAAs. ICI is the backbone of systemic therapy for HCC and enhance anti-tumor immunity by promoting T-cell regulatory cell depletion and reversal of T-cell exhaustion. Only one other case of HCV clearance with ICI is published but this is the first in the absence of DAA therapy. This finding suggests that ICI may restore anti-viral immunity in chronic infections and has implications for treatment decisions for HCV.