Decreased hepatocellular carcinoma tumor burden with the achievement of hepatitis C virus sustained virologic response: unlocking the potential of T-cell-mediated immunosurveillance

Anna S Griffith,1 Paul H Hayashi,1 Lauren MB Burke,2 Autumn J McRee1 1Department of Medicine, 2Department of Radiology, University of North Carolina at Chapel Hill Hospital, Chapel Hill, NC, USA Abstract: We describe two cases of patients with hepatitis C virus (HCV) treated with direct-acting antiviral (DAA) therapy who had dramatic improvement in hepatocellular carcinoma (HCC) tumor burden with DAA therapy alone. Both patients were diagnosed with HCC on screening magnetic resonance imaging shortly after beginning DAA therapy. Both patients achieved sustained virologic response (SVR) with dramatic improvement in HCC tumor burden on follow-up imaging without HCC treatment. Patients with multifocal or advanced HCC are infrequently treated with antiviral therapy for HCV. As a result, these cases provide unique insight into the ongoing debate regarding the impact of SVR on existing and recurrent HCC. We review the current literature regarding this debate, as well as the theory of immunosurveillance. We postulate that DAA therapy activates CD8+ T cells to induce a T-cell-mediated response and increased immunosurveillance to virus-induced liver cancer. Keywords: hepatocellular carcinoma, hepatitis C virus, sustained virologic response, direct-acting antiviral, T-cell-mediated immunosurveillanc

Long-term evolution of LI-RADS observations in HCV-related cirrhosis treated with direct-acting antivirals

Background & Aims The risk of progression of indeterminate observations to hepatocellular carcinoma (HCC) after direct-acting antivirals (DAA) is still undetermined. To assess whether DAA therapy changes the risk of progression of observations with low (LR-2), intermediate (LR-3) and high (LR-4) probability for HCC in cirrhotic patients and to identify predictors of progression. Methods This retrospective study included cirrhotic patients treated with DAA who achieved sustained virological response between 2015 and 2019. A total of 68 patients had pre-DAA indeterminate observations and at least six months CT/MRI follow-up before and after DAA. Two radiologists reviewed CT/MRI studies to categorize observations according to the LI-RADSv2018 and assess the evolution on subsequent follow-ups. Predictors of evolutions were evaluated by using the Cox proportional hazard model, Kaplan-Meier method and log-rank test. Results A total of 109 untreated observations were evaluated, including 31 (28.4%) LR-2, 67 (61.5%) LR-3 and 11 (10.1%) LR-4. During a median follow-up of 41 months, 17.4% and 13.3% of observations evolved to LR-5 or LR-M and LR-5, before and after DAA respectively (P = .428). There was no difference in rate of progression of neither LR-2 (P = 1.000), LR-3 (P = .833) or LR-4 (P = .505). At multivariate analysis, only initial LI-RADS category was an independent predictor of progression to LR-5 or LR-M for all observations (hazard ratio 6.75, P < .001), and of progression to LR-5 after DAA (hazard ratio 4.34, P = .047). Conclusions DAA therapy does not increase progression of indeterminate observations to malignant categories. The initial LI-RADS category is an independent predictor of observations upgrade