Direct-acting antiviral agents and risk of hepatocellular carcinoma: is it still a clinical dilemma?

Direct-acting antivirals (DAAs) revolutionised the treatment of chronic HCV-related disease achieving high rates of sustained virological response (SVR), also in more advanced patients, with a good safety profile and a proven positive effect on the reduction of risk of HCC occurrence. Nevertheless, patients with an history of successfully treated early HCC were initially excluded from pivotal trials. Although some initial retrospective studies, affected by several methodological issues, raised concerns regarding a possible harmful effect on the risk of HCC recurrence after antiviral therapy, more recent prospective studies and meta-analyses provided evidence that risk of HCC recurrence after DAA therapy is similar, or even lower, than that observed in patients treated with interferon or in DAA-untreated controls. In the future, a meta-analyses of individual patient data would be necessary to definitively close this clinical debate, as well as prospective studies assessing ‘true endpoints’, such as overall survival.