Sapena V, Enea M, Torres F, Celsa C, Rios J, Rizzo GEM, Nahon P, Mariño Z, Tateishi R, Minami T, Sangiovanni A, Forns X, Toyoda H, Brillanti S, Conti F, Degasperi E, Yu ML, Tsai PC, Jean K, El Kassas M, Shousha HI, Omar A, Zavaglia C, Nagata H, Nakagawa M, Asahina Y, Singal AG, Murphy C, Kohla M, Masetti C, Dufour JF, Merchante N, Cavalletto L, Chemello LL, Pol S, Crespo J, Calleja JL, Villani R, Serviddio G, Zanetto A, Shalaby S, Russo FP, Bielen R, Trevisani F, Cammà C, Bruix J, Cabibbo G, Reig M.
Gut. 2022 Mar;71(3):593-604. doi: 10.1136/gutjnl-2020-323663.
Objective: The benefit of direct-acting antivirals (DAAs) against 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: We 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 (100PY). 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 100PY in DAA-treated patients were 20 (95% CI 13.9 to 29.8, I2=74.6%) and 5.7 (2.5 to 15.3, I2=54.3), respectively. Predictive factors for recurrence were alpha-fetoprotein logarithm (relative risk (RR)=1.11, 95% CI 1.03 to 1.19; p=0.01, per 1 log of ng/mL), HCC recurrence history pre-DAA initiation (RR=1.11, 95% CI 1.07 to 1.16; p<0.001), performance status (2 vs 0, RR=4.35, 95% CI 1.54 to 11.11; 2 vs 1, RR=3.7, 95% CI 1.3 to 11.11; p=0.01) and tumour burden pre-HCC treatment (multifocal vs solitary nodule, RR=1.75, 95% CI 1.25 to 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 to 1.1; p=0.1).
Conclusion: Effects of DAA exposure on HCC recurrence risk remain inconclusive. Active clinical and radiological follow-up of patients with HCC after HCV eradication with DAA is justified.