Liver and Bile
Gut. 2022; 71(3):593–604
Hepatocellular carcinoma recurrence after direct-acting antiviral therapy: An individual patient data meta-analysis
Objective: The benefit of direct-acting antivirals (DAAs) against hepatitis C virus (HCV) following successful treatment of hepatocellular carcinoma (HCC) remains controversial. This meta-analysis of individual patient data assessed HCC recurrence risk following DAA administration.
Design: The authors pooled the data of 977 consecutive patients from 21 studies of HCV-related cirrhosis and HCC, who achieved complete radiological response after surgical/locoregional treatments and received DAAs (DAA group). Recurrence or death risk was expressed as HCC recurrence or death per 100 person-years. Propensity score-matched patients from the ITA.LI.CA. cohort (n = 328) served as DAA-unexposed controls (no-DAA group). Risk factors for HCC recurrence were identified using random-effects Poisson.
Results: Recurrence rate and death risk per 100 person-years in DAA-treated patients were 20 (95% confidence interval [CI]: 13.9–29.8, I² = 74.6%) and 5.7 (95% CI: 2.5–15.3, I² = 54.3), respectively. Predictive factors for recurrence were alpha-fetoprotein logarithm (relative risk [RR] = 1.11, 95% CI: 1.03–1.19; p = 0.01, per 1 log of ng/ml), HCC recurrence history pre-DAA initiation (RR = 1.11, 95% CI: 1.07–1.16; p < 0.001), performance status (2 vs. 0, RR = 4.35, 95% CI: 1.54–11.11; 2 vs. 1, RR = 3.7, 95% CI: 1.3–11.11; p = 0.01) and tumor burden pre-HCC treatment (multifocal vs. solitary nodule, RR = 1.75, 95% CI: 1.25–2.43; p < 0.001). No significant difference was observed in RR between the DAA-exposed and DAA-unexposed groups in propensity score-matched patients (RR = 0.64, 95% CI: 0.37–1.1; p = 0.1).
Conclusion: Effects of exposure to direct-acting antivirals (DAAs) on hepatocellular carcinoma (HCC) recurrence risk remain inconclusive. Active clinical and radiological follow-up of patients with HCC after hepatitis C virus eradication with DAAs is justified.