Chronic Hepatitis C Infection Treated with Direct-Acting Antiviral Agents and Occurrence/Recurrence of Hepatocellular Carcinoma: Does It Still Matter?

Abstract

Hepatitis C virus (HCV) infection is a significant risk factor for liver cirrhosis and hepatocellular carcinoma (HCC). Traditionally, the primary prevention strategy for HCV-associated HCC has focused on removing infection through antiviral regimes. Currently, highly effective direct-acting antivirals (DAAs) offer extraordinary success across all patient categories, including cirrhotics. Despite these advancements, recent studies have reported that even after sustained virologic response (SVR), individuals with advanced liver disease/cirrhosis at the time of DAA treatment may still face risks of HCC occurrence or recurrence. Based on this premise, this review tries to shed light on the multiple mechanisms that establish a tumorigenic environment, first, during chronic HCV infection and then, after eventual viral eradication by DAAs. Furthermore, it reviews evidence reported by recent observational studies stating that the use of DAAs is not associated with an increased risk of HCC development but rather, with a significantly lower chance of liver cancer compared with DAA-untreated patients. In addition, it seeks to provide some practical guidance for clinicians, helping them to manage HCC surveillance of patients who have achieved SVR with DAAs.

Keywords: advanced fibrosis; cirrhosis; direct-acting antiviral agents; hepatitis C virus; hepatocellular carcinoma; interferon; liver carcinogenesis; occurrence; recurrence; sustained virological response.

Figure 1

Available publications (updated to 1 October 2024) concerning the risk of hepatocellular carcinoma development after hepatitis C virus eradication with direct-acting antivirals. Trials include both clinical trials and randomized controlled trials; Cochrane Central Register of Controlled Trials is considered separately, after checking for possible overlaps with PubMed/MEDLINE databases. Reviews include both systematic and non-systematic reviews. The year 2024 refers to the literature published from 1 January 2024 to 30 September 2024. (a) Literature analysis including all stages of liver fibrosis; (b) literature analysis including only cirrhotic patients at the time of antiviral treatments.