Hepatocellular carcinoma recurrence after direct-acting antiviral therapy: an individual patient data meta-analysis

Victor Sapena, Marco Enea, Ferran Torres, Ciro Celsa, Jose Rios, Giacomo Emanuele Maria Rizzo, Pierre Nahon, Zoe Mariño, Ryosuke Tateishi, Tatsuya Minami, Angelo Sangiovanni, Xavier Forns, Hidenori Toyoda, Stefano Brillanti, Fabio Conti, Elisabetta Degasperi, Ming-Lung Yu, Pei-Chien Tsai, Kevin Jean, Mohamed El KassasHend Ibrahim Shousha, Ashraf Omar, Claudio Zavaglia, Hiroko Nagata, Mina Nakagawa, Yasuhiro Asahina, Amit G Singal, Caitlin Murphy, Mohamed Kohla, Chiara Masetti, Jean-François Dufour, Nicolas Merchante, Luisa Cavalletto, Liliana Lc Chemello, Stanislas Pol, Javier Crespo, Jose Luis Calleja, Rosanna Villani, Gaetano Serviddio, Alberto Zanetto, Sarah Shalaby, Francesco Paolo Russo, Rob Bielen, Franco Trevisani, Calogero Cammà, Jordi Bruix, Giuseppe Cabibbo, Maria Reig

Research output: Contribution to journalArticleResearchpeer-review

27 Citations (Scopus)


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.

Original languageEnglish
Early online date19 Mar 2021
Publication statusPublished - 19 Mar 2021


  • antiviral therapy
  • hepatocellular carcinoma
  • meta-analysis


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