Hepatitis C eradication improves oncologic and clinical outcomes in patients treated with Atezolizumab plus Bevacizumab

Background and Aims: Hepatitis C virus (HCV) is a key driver of hepatocellular carcinoma (HCC). However, the impact of HCV eradication on systemic therapy remains unclear. We aimed to assess the safety and efficacy of direct-acting antivirals (DAA) in patients treated with Atezolizumab plus Bevacizumab (AtezoBev). Methods: This retrospective multicentre study included patients with HCV-related unresectable/advanced HCC treated with AtezoBev between 2021 and 2024. Three groups of patients were compared: Group A (n = 22), concurrent DAA with AtezoBev; Group B (n = 95), antiviral therapy before AtezoBev; and Group C (n = 22), active infection. Results: Group A showed the longest median overall survival (42.8 months) compared to Group B (26.8 months; p = 0.03) and Group C (19.7 months; p = 0.01). Time to progression and progression-free survival were significantly prolonged in Group A versus Groups B and C. Moreover, Group A exhibited a higher disease control rate than the other groups. Post-DAA decompensation rates were significantly lower in Group A (4.5%) compared to Groups B (26.3%) and C (36.4%). Treatment-related adverse events of grade ≥ 3 were similar across groups. In the multivariate competing risk analysis with adjustment for time-dependent variables, achieving sustained virologic response during AtezoBev showed a protective effect against liver decompensation (sHR 0.02, p = 0.003) or tumour progression (sHR 0.14, p = 0.009), and was also associated with reduced mortality (HR 0.29, p = 0.005). Conclusions: Achieving a SVR during AtezoBev seems to improve oncologic outcomes and reduce liver decompensation in patients with unresectable/advanced HCC. An integrated therapeutic approach can optimise systemic treatment efficacy, particularly in patients eligible for conversion strategies. Trial Registration: Protocol ID: 5890.