Occurrence of hepatocellular carcinoma after direct-acting antiviral therapy for hepatitis C virus infection: literature review and risk analysis

ABSTRACT

Introduction: Concerns were raised about a high occurrence of hepatocellular carcinoma (HCC) after successful treatment of chronic hepatitis C (CHC) by direct-acting antivirals (DAAs).

Areas covered: The authors summarize the clinical studies reporting the occurrence rate and risk factors of HCC after DAAs in CHC.

Expert opinion: The recent introduction of all-oral DAAs has substantially changed the scenario of CHC, achieving a sustained virological response (SVR) in >90% of cases. Earlier concerns raised about an increasing incidence of HCC post-DAAs were flawed by large heterogeneity of patients, the limited number of well-designed prospective studies (only nine, up to date) and the inclusion of a large number of patients with advanced liver disease, previously excluded from interferon-based studies. Current data on DAAs have shown a lower risk of HCC development; however, they were unable to identify patients at greater risk for HCC occurrence after SVR. Surveillance strategy, likely lifelong, is mandatory in these patients according to general expert opinion.

KEYWORDS:

• Hepatocellular carcinoma
• HCC
• HCV
• DAA/direct-acting antivirals
• occurrence

Article highlights

• Direct-acting antiviral therapy for hepatitis C is indicated for all infected patients, especially in the setting of more advanced liver fibrosis.

• Previous concerns regarding an unexpected increase in the incidence of hepatocellular carcinoma following direct-acting antiviral therapies are unjustified, due to the large heterogeneity of previous study cohorts and the inclusion of a large population of patients with more advanced liver disease compared with the cohorts treated with interferon-based antiviral regimens.

• Direct-acting antiviral therapy for hepatitis C lowers the risk for hepatocellular carcinoma and death from other liver-related causes.

• It may be possible to achieve earlier identification of patients at major risk for hepatocarcinogenesis using an individualized clinical and biological profile.

• Surveillance following the eradication of viral infection should be mandatory in patients with advanced liver disease and a higher risk profile for hepatocellular carcinoma.This box summarizes key points contained in the article.

Declaration of interest

G Galati has received a travel grant from Bayer. M Iavarone has received speaker honoraria from Bayer, Gilead, Janssen, BTG, AbbVie, and Merck, and he is a consultant for Bayer and BTG. F Trevisani is in the advisory board of Bayer, Alfasigma, Bristol-Myers Squibb and Sirtex. A Vitale and G Cabibbo are in the advisory board of Bayer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was not funded.