HCC: Does Exposure to Direct-Acting Antivirals Affect Recurrence Risk?

Investigators conducted an international, multicenter meta-analysis to assess HCC recurrence risk in patients treated with DAAs.

The risk for recurrence of hepatocellular carcinoma (HCC) does not vary significantly between patients treated with direct-acting antivirals (DAAs) and patients untreated for hepatitis C virus (HCV) infection, according to study results published in Gut.

Although it is known that the use of DAAs to treat HCV does not eradicate the risk of HCC recurrence following effective surgery, the benefits of DAAs in this population remain unclear. Previous studies in North America suggested that these patients have improved survival and no increase in the recurrence of HCC. However, there is a lack of international data. To address this knowledge gap, a team of investigators conducted an international, multicenter meta-analysis to determine the influence of DAAs on recurrence risk of HCC in patients who have had complete response to therapy.

Using data from 12 retrospective studies and 9 prospective studies, 977 patients who were treated with DAAs were analyzed. The majority of patients were men (63%) and the median age was 67.9 years. At diagnosis, 38.6% of patients had solitary HCC, 7.1% had multifocal HCC, and less than 0.5% of patients had extrahepatic spread or vascular invasion. The most frequently reported treatments were ablation (47.3%), resection (31%), and chemoembolization (15.3%).

The median follow-up time for the overall group was 15 months, at which time 41.8% of patients developed recurrent HCC and 12.9% of patients died. The pooled HCC recurrence rate was 20 per 100 patient-years (100PY) and the pooled death rate was 5.7 per 100PY.

In a multivariate analysis, the observed predicted factors for recurrence of HCC included the logarithm of α-fetoprotein (relative risk [RR], 1.11; P =.01), the number of HCC recurrences prior to DAA initiation (RR, 1.11; P <.001), Eastern Cooperative Oncology Group-performance status (2 vs 0: RR, 4.35; P =.01; 2 vs 1: RR, 3.7; P =.01), and tumor burden before HCC treatment (multifocal vs solitary nodule, RR, 1.75; P <.001).

In propensity score-matched patients, there was no significant difference in RR between patients who were exposed or unexposed to DAAs (RR, 0.64; P =.1).

“Studies with longer follow-up time should define if the recurrence risk is modified beyond this time frame and confirm the findings observed in the survival analysis,” the investigators noted. “Our findings suggest that active clinical and radiological follow-up is fully justified in this population for whom no effective adjuvant treatment is available.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Sapena V, Enea M, Torres F, et al. Hepatocellular carcinoma recurrence after direct-acting antiviral therapy: an individual patient data meta-analysis. Gut. Published online March 19, 2021. doi: 10.1136/gutjnl-2020-323663