Hepatocellular carcinoma remains a leading cause of cancer-related deaths worldwide, with chronic hepatitis C virus (HCV) infection driving both its development and progression. The introduction of direct-acting antivirals (DAAs) has revolutionised HCV treatment, achieving sustained virological response (SVR) in most patients and reducing liver inflammation, fibrosis, and the risk of hepatocellular carcinoma. However, the role of HCV eradication in patients already diagnosed with advanced hepatocellular carcinoma has been less clear, particularly when systemic therapies such as immune checkpoint inhibitors are used.
Concurrent therapy for Hepatocellular Carcinoma
A recent study explored the impact of HCV eradication in patients with unresectable or advanced hepatocellular carcinoma treated with the immunotherapy combination of atezolizumab and bevacizumab (AtezoBev). The results showed that DAA therapy can be safely administered alongside systemic treatment, without increasing treatment-related adverse events. Importantly, patients who achieved SVR during immunotherapy had significantly improved overall survival, time to progression, and progression-free survival, along with reduced risks of liver decompensation.
These findings are especially relevant for unresectable hepatocellular carcinoma, where maintaining liver function and delaying tumour progression can open the door to conversion strategies, such as curative surgery or transplantation. By removing the persistent hepatic insult caused by active HCV infection, antiviral therapy appears to strengthen the effectiveness of immunotherapy and improve clinical outcomes.
Biological Rationale and Clinical Impact
The biological explanation lies in how HCV eradication reshapes the tumour microenvironment. Chronic HCV promotes immune exhaustion and a pro-inflammatory cytokine milieu, limiting anti-tumour responses. Achieving SVR reverses some of these effects, restoring T-cell function, reducing immunosuppressive signalling, and enhancing responsiveness to checkpoint blockade. This synergistic effect suggests that combining DAA therapy with immunotherapy could represent an optimal approach for patients with advanced hepatocellular carcinoma.
While the study was limited by its retrospective design and small sample size, the evidence strongly supports offering antiviral treatment even in advanced disease. Treating HCV not only improves liver health but also enhances the efficacy of systemic therapy, reinforcing the importance of integrated care strategies in hepatocellular carcinoma management.
Reference
Stella L et al. Hepatitis C eradication improves oncologic and clinical outcomes in patients treated with atezolizumab plus bevacizumab. Liver Int. 2025;45(10):e70362.
