Author information

Collaborators

• Italian Liver Cancer (ITA.LI.CA) group: 

Anna Sartori, Angela Imondi, Barbara Penzo, Maurizio Biselli, Paolo Caraceni, Francesca Garuti, Annagiulia Gramenzi, Andrea Neri, Davide Ramboldi, Valentina Santi, Alessandro Granito, Luca Muratori, Fabio Piscaglia, Vito Sansone, Francesco Tovoli, Elton Dajti, Giovanni Marasco, Federico Ravaioli, Alberta Cappelli, Rita Golfieri, Cristina Mosconi, Matteo Renzulli, Ester Marina Cela, Antonio Facciorusso, Valentina Cacciato, Edoardo Casagrande, Alessandro Moscatelli, Gaia Pellegatta, Nicoletta de Matthaeis, Gloria Allegrini, Valentina Lauria, Giorgia Ghittoni, Giorgio Pelecca, Fabrizio Chegai, Fabio Coratella, Mariano Ortenzi, Elisabetta Biasini, Andrea Olivani, Alessandro Inno, Fabiana Marchetti, Anita Busacca, Giuseppe Cabibbo, Calogero Cammà, Vincenzo Di Martino, Giacomo Emanuele Maria Rizzo, Maria Stella Franzè, Carlo Saitta, Assunta Sauchella, Vittoria Bevilacqua, Dante Berardinelli, Alberto Borghi, Andrea Casadei Gardini, Fabio Conti, Alessandro Cucchetti, Anna Chiara Dall'Aglio, Giorgio Ercolani, Claudia Campani, Chiara Di Bonaventura, Stefano Gitto, Pietro Coccoli Antonio Malerba, Mario Capasso, Maria Guarino, Filippo Oliveri, Veronica Romagnoli, Alessandro Di Bucchianico

Affiliations

• ¹Department of Surgery, Oncology and Gastroenterology, University of Padua, Padova, Italy.
• ²Liver Disease and Transplant Unit, Polytechnic University of Marche, Ancona, Italy gsvegliati@gmail.com.
• ³Obesity Center, Polytechnic University of Marche, Ancona, Italy.
• ⁴Department of Gastroenterology, Azienda Ospedaliera Marche Nord Pesaro, Pesaro, Italy.
• ⁵Liver Disease and Transplant Unit, Polytechnic University of Marche, Ancona, Italy.
• ⁶Department of Gastroenterology, Polytechnic University of Marche, Ancona, Italy.
• ⁷School of Mathematics and Statistics University of Canterbury, Statistics University of Canterbury, Canterbury, New Zealand.
• ⁸Department of Internal Medicine, Gastroenterology Unit, University of Genova, IRCCS Policlinico San Martino, Genoa, Italy.
• ⁹Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
• ¹⁰Gastroenterology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy.
• ¹¹Medicine Unit, Azienda Ospedaliera Bolognini, Seriate, Italy.
• ¹²Gastroenterology Unit, Ospedale Belcolle, Viterbo, Italy.
• ¹³Department of Medical and Surgical Sciences, Internal Medicine-Zoli Unit, Alma Mater Studiorum - Università di Bologna, Padova, Italy.
• ¹⁴Gastroenterology and Digestive Endoscopy Unit, Foggia University Hospital, Foggia, Puglia, Italy.
• ¹⁵Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, PROMISE, Gastroenterology & Hepatology Unit, University of Palermo, Palermo, Italy.
• ¹⁶Department of Experimental and Clinical Medicine, Internal Medicine and Hepatology Unit, University of Florence, Florence, Italy.
• ¹⁷Gastroenterology Unit, Ospedale Generale Regionale di Bolzano, Bolzano, Italy.
• ¹⁸Department of Clinical Medicine and Surgery, Gastroenterology Unit, University of Naples Federico II, Portici, Italy.
• ¹⁹Internal Medicine, Gastroenterology, and Liver Unit, University Hospital Agostino Gemelli, Roma, Lazio, Italy.
• ²⁰Department of Internal Medicine, Ospedale degli Infermi di Faenza, Faenza, Emilia Romagna, Italy.
• ²¹Infectious Diseases and Hepatology Unit, Azienda Ospedaliero-Universitaria di Parma, Parma, Emilia-Romagna, Italy.
• ²²Gastroenterology Unit, IRCCS Ospedale Sacro Cuore Don Calabria, Negrar, Veneto, Italy.
• ²³Department of Clinical Medicine and Surgery, Hepato-Gastroenterology Unit, Federico II University Hospital, Napoli, Italy.
• ²⁴Clinical and Experimental Medicine, University Hospital of Messina, Messina, Italy.
• ²⁵Division of Gastroenterology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
• ²⁶Department of Clinical and Experimental Medicine, Universita degli Studi di Sassari, Sassari, Italy.
• ²⁷Department of Clinical and Experimental Medicine, Hepatology and Liver Physiopathology Laboratory and Internal Medicine, University of Pisa, Pisa, Italy.
• ²⁸Division of Medical Semeiotics, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
• ²⁹Internal Medicine and Gastroenterology, Fondazione Policlinico Gemelli, Rome, Italy.
• ³⁰Internal Medicine, Universita Cattolica del Sacro Cuore, Roma, Italy.
• ³¹Department of Medical & Surgical Sciences, University of Bologna Hospital of Bologna Sant'Orsola-Malpighi Polyclinic, Bologna, Italy.

^#Contributed equally.

Abstract

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) represents a new inclusive definition of the whole spectrum of liver diseases associated to metabolic disorders. The main objective of this study was to compare patients with MAFLD and non-MAFLD with hepatocellular carcinoma (HCC) included in a nationally representative cohort.

Methods: We analysed 6882 consecutive patients with HCC enrolled from 2002 to 2019 by 23 Italian Liver Cancer centres to compare epidemiological and future trends in three subgroups: pure, single aetiology MAFLD (S-MAFLD); mixed aetiology MAFLD (metabolic and others, M-MAFLD); and non-MAFLD HCC.

Results: MAFLD was diagnosed in the majority of patients with HCC (68.4%). The proportion of both total MAFLD and S-MAFLD HCC significantly increased over time (from 50.4% and 3.6% in 2002-2003, to 77.3% and 28.9% in 2018-2019, respectively, p<0.001). In Italy S-MAFLD HCC is expected to overcome M-MAFLD HCC in about 6 years. Patients with S-MAFLD HCC were older, more frequently men and less frequently cirrhotic with clinically relevant portal hypertension and a surveillance-related diagnosis. They had more frequently large tumours and extrahepatic metastases. After weighting, and compared with patients with non-MAFLD, S-MAFLD and M-MAFLD HCC showed a significantly lower overall (p=0.026, p=0.004) and HCC-related (p<0.001, for both) risk of death. Patients with S-MAFLD HCC showed a significantly higher risk of non-HCC-related death (p=0.006).

Conclusions: The prevalence of MAFLD HCC in Italy is rapidly increasing to cover the majority of patients with HCC. Despite a less favourable cancer stage at diagnosis, patients with MAFLD HCC have a lower risk of HCC-related death, suggesting reduced cancer aggressiveness.