INTRODUCTION: Hepatocellular carcinoma represents a relevant cause of cancer mortality globally, with hepatitis C virus infection accounting for 25-30% of cases. The advent of direct-acting antivirals has transformed HCV management, yet treatment of patients with concurrent or prior HCC presents unique pharmacotherapeutic challenges. AREAS COVERED: This review examines DAA efficacy and safety in HCC patients, addressing the now-resolved controversy regarding potential increased HCC recurrence. We analyze drug-drug interactions between DAAs and systemic HCC therapies, including tyrosine kinase inhibitors and immune checkpoint inhibitors. The impact of sustained virological response on oncological outcomes is evaluated, alongside practical guidance for special populations. EXPERT OPINION: Current evidence supports universal HCV treatment in HCC patients, with SVR rates approaching 90% and demonstrated reductions in both recurrence and mortality. The recurrence controversy has been definitively resolved through rigorous meta-analyses. Future research should prioritize prospective pharmacokinetic studies and optimization of treatment sequencing.
Moriello et al. (2026) studied this question.