Author information

• ¹Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clínic de Barcelona, IDIBAPS, Universidad de Barcelona, CIBEREHD, Hospital Clinic de Barcelona, Barcelona, Spain.
• ²Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, PROMISE, Gastroenterology & Hepatology Unit, University of Palermo, Palermo, Sicilia, Italy.
• ³Biostatistics and Data Management Core Facility, IDIBAPS, Hospital Clinic Barcelona, Barcelona, Spain.
• ⁴Biostatistics Unit, Faculty of Medicine, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.
• ⁵Department of Surgical, Oncological and Oral Sciences (Di.Chir.On.S.), University of Palermo, Palermo, Sicilia, Italy.
• ⁶AP-HP, Hôpital Jean Verdier, Service d'Hépatologie, Bondy; Université Paris 13, Sorbonne Paris Cité, "Equipe labellisée Ligue Contre le Cancer", F-93206 Saint-Denis; Inserm, UMR-1162, "Génomique fonctionnelle des tumeurs solides", F-75000, Bondy, France.
• ⁷Liver Unit, Hospital Clinic de Barcelona, IDIBAPS, University of Barcelona, CIBEREHD, Barcelona, Spain.
• ⁸Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
• ⁹Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Maggiore Hospital, University of Milan, Milan, Italy.
• ¹⁰CRC "A.M. and A. Migliavacca" Center for Liver Disease, Milan, Italy.
• ¹¹Gastroenterology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan.
• ¹²Department of Medical and Surgical Sciences (DIMEC), Research Centre for the Study of Hepatitis, University of Bologna, Bologna, Italy.
• ¹³Hepatobiliary Division, Department of Internal Medicine and Hepatitis, Center Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
• ¹⁴Faculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
• ¹⁵Laboratoire MESuRS (EA 4628), Conservatoire National Des Arts et Métiers, Paris, France.
• ¹⁶Unité PACRI, Institut Pasteur, Conservatoire National des Arts et Métiers, Paris, France.
• ¹⁷Endemic Medicine, Faculty of Medicine, Helwan University, Cairo, Egypt.
• ¹⁸Endemic Medicine and Hepato-Gastroenterology, Faculty of Medicine, Cairo University, Cairo, Egypt.
• ¹⁹Department of Hepatology and Gastroenterology, Liver Unit, Niguarda Hospital, Milano, Lombardia, Italy.
• ²⁰Gastroenterology and Hepatology, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
• ²¹Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
• ²²Institute of Education, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
• ²³Department of Gastroenterology and Hepatology, Liver Disease Control, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
• ²⁴Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, Texas, USA.
• ²⁵Hepatology, National Liver Institute, Shebin El-Kom, Egypt.
• ²⁶Liver and Transplant Unit, Policlinico Tor Vergata, Rome, Italy.
• ²⁷Hepatology, Department of Clinical Research, University Clinic for Visceral Surgery and Medicine Inselspital, Bern, Switzerland.
• ²⁸Hepatology, Department of Clinical Research, University of Bern, Bern, Switzerland.
• ²⁹Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario de Valme, Seville, Spain.
• ³⁰Department of Medicine-DIMED, Padua University, University Hospital, Clinica Medica 5, Refering Center for Liver Diseases, Padova, Italy.
• ³¹l'Agence de recherche ANRS (France REcherche Nord&Sud Sida-HIV Hépatites), Paris, France.
• ³²Gastroenterology and Hepatology Service, Hospital Universitario Marques de Valdecilla, IDIVAL, Santander, Spain.
• ³³Facultad de Medicina, Universidad de Cantabria, Santander, Cantabria, Spain.
• ³⁴Gastroenterology and Hepatology, IDIPHIM, Hospital Universitario Puerta de Hierro Majadahonda, Majadahonda, Spain.
• ³⁵(CIBEREHD), Instituto de Salud Carlos III, Centro de Investigacion Biomedica en Red Enfermedades Hepaticas y Digestivas, Madrid, Spain.
• ³⁶Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
• ³⁷Gastroenterology/Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology Unit, University of Padova, Padova, Italy.
• ³⁸Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Limburg, Belgium.
• ³⁹Department of Gastro-Enterology and Hepatology, Ziekenhuis Oost-Limburg, Genk, Limburg, Belgium.
• ⁴⁰Department of Medical and Surgical Sciences, Semeiotics Unit, Alma Mater Studiorum-University of Bologna, Bologna, Italy.
• ⁴¹Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, PROMISE, Gastroenterology & Hepatology Unit, University of Palermo, Palermo, Sicilia, Italy MREIG1@clinic.cat giuseppe.cabibbo78@gmail.com.
• ⁴²Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clínic de Barcelona, IDIBAPS, Universidad de Barcelona, CIBEREHD, Hospital Clinic de Barcelona, Barcelona, Spain MREIG1@clinic.cat giuseppe.cabibbo78@gmail.com.

^#Contributed equally.

Abstract

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.