Reduction of the Risk of Hepatocellular Carcinoma over Time Using Direct-Acting Antivirals: A Propensity Score Analysis of a Real-Life Cohort (PITER HCV)
Maria Giovanna Quaranta,
Luisa Cavalletto,
Francesco Paolo Russo,
Vincenza Calvaruso,
Luigina Ferrigno,
Alberto Zanetto,
Benedetta Mattioli,
Roberta D’Ambrosio,
Valentina Panetta,
Giuseppina Brancaccio,
Giovanni Raimondo,
Maurizia Rossana Brunetto,
Anna Linda Zignego,
Carmine Coppola,
Andrea Iannone,
Elisa Biliotti,
Elena Rosselli Del Turco,
Marco Massari,
Anna Licata,
Francesco Barbaro,
Marcello Persico,
Filomena Morisco,
Maurizio Pompili,
Federica Cerini,
Massimo Puoti,
Teresa Santantonio,
Antonio Craxì,
Loreta A. Kondili,
Liliana Chemello,
on behalf of PITER Collaborating Investigators
Affiliations
Maria Giovanna Quaranta
Center for Global Health, Istituto Superiore di Sanità (ISS), 00161 Rome, Italy
Luisa Cavalletto
Department of Medicine-DIMED, Clinica Medica 5, Refering Regional Center for Liver Diseases, University Hospital, Padua University, 35122 Padova, Italy
Francesco Paolo Russo
Department of Surgery, Oncology and Gastroenterology, Gastroenterology Unit, University of Padua, 35122 Padua, Italy
Vincenza Calvaruso
Gastroenterology and Hepatology Unit, PROMISE, University of Palermo, 90133 Palermo, Italy
Luigina Ferrigno
Center for Global Health, Istituto Superiore di Sanità (ISS), 00161 Rome, Italy
Alberto Zanetto
Department of Surgery, Oncology and Gastroenterology, Gastroenterology Unit, University of Padua, 35122 Padua, Italy
Benedetta Mattioli
Center for Global Health, Istituto Superiore di Sanità (ISS), 00161 Rome, Italy
Roberta D’Ambrosio
Division of Gastroenterology and Hepatology, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
Infectious Diseases Unit, Department of Molecular Medicine, University of Padua,35122 Padua, Italy
Giovanni Raimondo
Department of Internal Medicine, University Hospital of Messina, 98122 Messina, Italy
Maurizia Rossana Brunetto
Department of Clinical and Experimental Medicine, University Hospital of Pisa, 56126 Pisa, Italy
Anna Linda Zignego
Department of Experimental and Clinical Medicine, Interdepartmental Centre MASVE, University of Florence, 50121 Florence, Italy
Carmine Coppola
Department of Hepatology, Gragnano Hospital, 80054 Naples, Italy
Andrea Iannone
Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, 70121 Bari, Italy
Elisa Biliotti
Infectious and Tropical Medicine Unit, Department of Public Health and Infectious Diseases, “Policlinico Umberto I” Hospital, Sapienza University of Rome, 00161 Rome, Italy
Elena Rosselli Del Turco
Infectious Diseases Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
Marco Massari
Malattie Infettive, Azienda Unità Sanitaria Locale, IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy
Anna Licata
Infectious Diseases Unit, DIBIMIS, University of Palermo, 90133 Palermo, Italy
Francesco Barbaro
Department of Medicine, Infectious Diseases Unit, University of Padua, 35122 Padua, Italy
Marcello Persico
Internal Medicine and Hepatology Division, Department of Medicine, Surgery and Dentistry, “Scuola Medica Salernitana”, University of Salerno, 84084 Baronissi, Italy
Filomena Morisco
Gastroenterology Unit, Federico II University, 80138 Naples, Italy
Maurizio Pompili
Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo Agostino Gemelli, 00136 Rome, Italy
Federica Cerini
Department of Clinical Sciences and Community Health, University of Milan, Hepatology Unit, San Giuseppe Hospital, 20123 Milan, Italy
Massimo Puoti
Infectious Disease Unit, Niguarda Hospital, 20142 Milan, Italy
Teresa Santantonio
Infectious Diseases Unit, Department of Clinical and Surgical Sciences, University of Foggia, AOU Policlinico Riuniti Foggia, 71122 Foggia, Italy
Antonio Craxì
Gastroenterology and Hepatology Unit, PROMISE, University of Palermo, 90133 Palermo, Italy
Loreta A. Kondili
Center for Global Health, Istituto Superiore di Sanità (ISS), 00161 Rome, Italy
Liliana Chemello
Department of Medicine-DIMED, Clinica Medica 5, Refering Regional Center for Liver Diseases, University Hospital, Padua University, 35122 Padova, Italy
The treatment of hepatitis C virus (HCV) with direct-acting antivirals (DAA) leads to high sustained virological response (SVR) rates, but hepatocellular carcinoma (HCC) risk persists in people with advanced liver disease even after SVR. We weighted the HCC risk in people with cirrhosis achieving HCV eradication through DAA treatment and compared it with untreated participants in the multicenter prospective Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. Propensity matching with inverse probability weighting was used to compare DAA-treated and untreated HCV-infected participants with liver cirrhosis. Kaplan–Meier analysis and competing risk regression analysis were performed. Within the first 36 months, 30 de novo HCC cases occurred in the untreated group (n = 307), with a weighted incidence rate of 0.34% (95%CI: 0.23–0.52%), compared to 63 cases among SVR patients (n = 1111), with an incidence rate of 0.20% (95%CI: 0.16–0.26%). The 12-, 24-, and 36-month HCC weighted cumulative incidence rates were 6.7%, 8.4%, and 10.0% in untreated cases and 2.3%, 4.5%, and 7.0% in the SVR group. Considering death or liver transplantation as competing events, the untreated group showed a 64% higher risk of HCC incidence compared to SVR patients (SubHR 1.64, 95%CI: 1.02–2.62). Other variables independently associated with the HCC occurrence were male sex, increasing age, current alcohol use, HCV genotype 3, platelet count ≤ 120,000/µL, and albumin ≤ 3.5 g/dL. In real-life practice, the high efficacy of DAA in achieving SVR is translated into high effectiveness in reducing the HCC incidence risk.
