Hepatocellular carcinoma recurrence after direct-acting antiviral therapy: an individual patient data meta-analysis
Victor Sapena
(1)
,
Marco Enea
(2)
,
Ferran Torres
(1)
,
Ciro Celsa
(2)
,
Jose Rios
(1)
,
Giacomo Emanuele Maria Rizzo
(2)
,
Pierre Nahon
(3, 4)
,
Zoe Mariño
(5)
,
Ryosuke Tateishi
(6)
,
Tatsuya Minami
(6)
,
Angelo Sangiovanni
(7)
,
Xavier Forns
(5)
,
Hidenori Toyoda
,
Stefano Brillanti
(8)
,
Fabio Conti
(8)
,
Elisabetta Degasperi
(7)
,
Ming-Lung Yu
(9)
,
Pei-Chien Tsai
(9)
,
Kévin Jean
(10, 11)
,
Mohamed El Kassas
(12)
,
Hend Ibrahim Shousha
(13)
,
Ashraf Omar
(13)
,
Claudio Zavaglia
,
Hiroko Nagata
(14)
,
Mina Nakagawa
(14)
,
Yasuhiro Asahina
(14)
,
Amit Singal
(15)
,
Caitlin Murphy
(15)
,
Mohamed Kohla
(16)
,
Chiara Masetti
(17)
,
Jean-François Dufour
(18)
,
Nicolas Merchante
,
Luisa Cavalletto
(19)
,
Liliana Chemello
(19)
,
Stanislas Pol
(20)
,
Javier Crespo
(21)
,
Jose Luis Calleja
(22)
,
Rosanna Villani
(23)
,
Gaetano Serviddio
(23)
,
Alberto Zanetto
(19)
,
Sarah Shalaby
(19)
,
Francesco Paolo Russo
(19)
,
Rob Bielen
(24)
,
Franco Trevisani
(8)
,
Calogero Cammà
(2)
,
Jordi Bruix
(5)
,
Giuseppe Cabibbo
(2)
,
Maria Reig
(5)
1
UB -
Universitat de Barcelona
2 Università degli studi di Palermo - University of Palermo
3 U1162 - Génomique Fonctionnelle des Tumeurs Solides
4 Hôpital Jean Verdier [AP-HP]
5 IDIBAPS - Institut d'Investigacions Biomèdiques August Pi i Sunyer
6 UTokyo - The University of Tokyo
7 UNIMI - Università degli Studi di Milano = University of Milan
8 UNIBO - Alma Mater Studiorum Università di Bologna = University of Bologna
9 National Kaohsiung University of Science and Technology [Taiwan]
10 MESuRS - Laboratoire Modélisation, épidémiologie et surveillance des risques sanitaires
11 PACRI - Pasteur-Cnam Risques infectieux et émergents
12 Helwan University [Caire]
13 Cairo University - Faculty of Medicine
14 TMDU - Tokyo Medical and Dental University [Japan]
15 University of Texas Southwestern Medical Center
16 National Liver Institute [Menoufia, Egypt]
17 PoliclinicoTor Vergata - Fondatione PTV
18 Inselspital - Bern University Hospital [Berne]
19 Unipd - Università degli Studi di Padova = University of Padua
20 ANRS France Recherche Nord & sud Sida-hiv hépatites
21 Universidad de Cantabria [Santander]
22 CIBERehd - Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas
23 Unifg - Università degli Studi di Foggia = University of Foggia
24 UHasselt - Hasselt University
2 Università degli studi di Palermo - University of Palermo
3 U1162 - Génomique Fonctionnelle des Tumeurs Solides
4 Hôpital Jean Verdier [AP-HP]
5 IDIBAPS - Institut d'Investigacions Biomèdiques August Pi i Sunyer
6 UTokyo - The University of Tokyo
7 UNIMI - Università degli Studi di Milano = University of Milan
8 UNIBO - Alma Mater Studiorum Università di Bologna = University of Bologna
9 National Kaohsiung University of Science and Technology [Taiwan]
10 MESuRS - Laboratoire Modélisation, épidémiologie et surveillance des risques sanitaires
11 PACRI - Pasteur-Cnam Risques infectieux et émergents
12 Helwan University [Caire]
13 Cairo University - Faculty of Medicine
14 TMDU - Tokyo Medical and Dental University [Japan]
15 University of Texas Southwestern Medical Center
16 National Liver Institute [Menoufia, Egypt]
17 PoliclinicoTor Vergata - Fondatione PTV
18 Inselspital - Bern University Hospital [Berne]
19 Unipd - Università degli Studi di Padova = University of Padua
20 ANRS France Recherche Nord & sud Sida-hiv hépatites
21 Universidad de Cantabria [Santander]
22 CIBERehd - Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas
23 Unifg - Università degli Studi di Foggia = University of Foggia
24 UHasselt - Hasselt University
Pierre Nahon
- Fonction : Auteur
- PersonId : 801099
- ORCID : 0000-0003-2489-0768
- IdRef : 074345273
Hidenori Toyoda
- Fonction : Auteur
Kévin Jean
- Fonction : Auteur
- PersonId : 173689
- IdHAL : kevin-jean
- ORCID : 0000-0001-6462-7185
- IdRef : 17816903X
Claudio Zavaglia
- Fonction : Auteur
Jean-François Dufour
- Fonction : Auteur
- PersonId : 801980
- ORCID : 0000-0002-8062-1346
Nicolas Merchante
- Fonction : Auteur
Stanislas Pol
- Fonction : Auteur
- PersonId : 755799
- ORCID : 0000-0001-9772-9591
Alberto Zanetto
- Fonction : Auteur
- PersonId : 806664
- ORCID : 0000-0002-6734-7178
Résumé
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.