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Hepatology
Original research
Epidemiological trends and trajectories of MAFLD-associated hepatocellular carcinoma 2002–2033: the ITA.LI.CA database
  1. Alessandro Vitale1,
  2. Gianluca Svegliati-Baroni2,3,
  3. Alessio Ortolani4,
  4. Monica Cucco2,5,
  5. Giulio V Dalla Riva6,
  6. Edoardo G Giannini7,
  7. Fabio Piscaglia8,
  8. Gianludovico Rapaccini9,
  9. Mariella Di Marco10,
  10. Eugenio Caturelli11,
  11. Marco Zoli12,
  12. Rodolfo Sacco13,
  13. Giuseppe Cabibbo14,
  14. Fabio Marra15,
  15. Andrea Mega16,
  16. Filomena Morisco17,
  17. Antonio Gasbarrini18,
  18. Francesco Giuseppe Foschi19,
  19. Gabriele Missale20,
  20. Alberto Masotto21,
  21. Gerardo Nardone22,
  22. Giovanni Raimondo23,
  23. Francesco Azzaroli24,
  24. Gianpaolo Vidili25,
  25. Filippo Oliveri26,
  26. Filippo Pelizzaro1,
  27. Rafael Ramirez Morales1,
  28. Umberto Cillo1,
  29. Franco Trevisani27,
  30. Luca Miele28,29,
  31. Giulio Marchesini30,
  32. Fabio Farinati1
  33. for the Italian Liver Cancer (ITA.LI.CA) group
    1. 1Department of Surgery, Oncology and Gastroenterology, University of Padua, Padova, Italy
    2. 2Liver Disease and Transplant Unit, Polytechnic University of Marche, Ancona, Italy
    3. 3Obesity Center, Polytechnic University of Marche, Ancona, Italy
    4. 4Department of Gastroenterology, Azienda Ospedaliera Marche Nord Pesaro, Pesaro, Italy
    5. 5Department of Gastroenterology, Polytechnic University of Marche, Ancona, Italy
    6. 6School of Mathematics and Statistics University of Canterbury, Statistics University of Canterbury, Canterbury, New Zealand
    7. 7Department of Internal Medicine, Gastroenterology Unit, University of Genova, IRCCS Policlinico San Martino, Genoa, Italy
    8. 8Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
    9. 9Gastroenterology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy
    10. 10Medicine Unit, Azienda Ospedaliera Bolognini, Seriate, Italy
    11. 11Gastroenterology Unit, Ospedale Belcolle, Viterbo, Italy
    12. 12Department of Medical and Surgical Sciences, Internal Medicine–Zoli Unit, Alma Mater Studiorum - Università di Bologna, Padova, Italy
    13. 13Gastroenterology and Digestive Endoscopy Unit, Foggia University Hospital, Foggia, Puglia, Italy
    14. 14Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, PROMISE, Gastroenterology & Hepatology Unit, University of Palermo, Palermo, Italy
    15. 15Department of Experimental and Clinical Medicine, Internal Medicine and Hepatology Unit, University of Florence, Florence, Italy
    16. 16Gastroenterology Unit, Ospedale Generale Regionale di Bolzano, Bolzano, Italy
    17. 17Department of Clinical Medicine and Surgery, Gastroenterology Unit, University of Naples Federico II, Portici, Italy
    18. 18Internal Medicine, Gastroenterology, and Liver Unit, University Hospital Agostino Gemelli, Roma, Lazio, Italy
    19. 19Department of Internal Medicine, Ospedale degli Infermi di Faenza, Faenza, Emilia Romagna, Italy
    20. 20Infectious Diseases and Hepatology Unit, Azienda Ospedaliero-Universitaria di Parma, Parma, Emilia-Romagna, Italy
    21. 21Gastroenterology Unit, IRCCS Ospedale Sacro Cuore Don Calabria, Negrar, Veneto, Italy
    22. 22Department of Clinical Medicine and Surgery, Hepato-Gastroenterology Unit, Federico II University Hospital, Napoli, Italy
    23. 23Clinical and Experimental Medicine, University Hospital of Messina, Messina, Italy
    24. 24Division of Gastroenterology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
    25. 25Department of Clinical and Experimental Medicine, Universita degli Studi di Sassari, Sassari, Italy
    26. 26Department of Clinical and Experimental Medicine, Hepatology and Liver Physiopathology Laboratory and Internal Medicine, University of Pisa, Pisa, Italy
    27. 27Division of Medical Semeiotics, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
    28. 28Internal Medicine and Gastroenterology, Fondazione Policlinico Gemelli, Rome, Italy
    29. 29Internal Medicine, Universita Cattolica del Sacro Cuore, Roma, Italy
    30. 30Department of Medical & Surgical Sciences, University of Bologna Hospital of Bologna Sant'Orsola-Malpighi Polyclinic, Bologna, Italy
    1. Correspondence to Professor Gianluca Svegliati-Baroni, Liver Disease and Transplant Unit, Polytechnic University of Marche, Ancona, Marche, Italy; gsvegliati{at}gmail.com

    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.

    • hepatocellular carcinoma
    • nonalcoholic steatohepatitis

    Data availability statement

    Data are available upon reasonable request. The ITA.LI.CA database management conforms to the past and the current Italian legislation regarding privacy, and the present study conforms to the ethical guidelines of the Declaration of Helsinki. Approval for the study was obtained from the Institutional Review Board of the participating centres.

    https://doi.org/10.1136/gutjnl-2021-324915

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      Data availability statement

      Data are available upon reasonable request. The ITA.LI.CA database management conforms to the past and the current Italian legislation regarding privacy, and the present study conforms to the ethical guidelines of the Declaration of Helsinki. Approval for the study was obtained from the Institutional Review Board of the participating centres.

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      Footnotes

      • AV and GS-B contributed equally.

      • Collaborators Department of Surgery, Oncology and Gastroenterology, University of Padua: Anna Sartori, Angela Imondi, Barbara Penzo. Department of Medical and Surgical Sciences, Semeiotics Unit, University of Bologna: Maurizio Biselli, Paolo Caraceni, Francesca Garuti, Annagiulia Gramenzi, Andrea Neri, Davide Ramboldi, Valentina Santi. Azienda Ospedaliero-Universitaria S. Orsola-Malpighi, Internal Medicine–Piscaglia Unit, Bologna, Italy: Alessandro Granito, Luca Muratori, Fabio Piscaglia, Vito Sansone, Francesco Tovoli. Department of Surgical and Medical Sciences, Gastroenterology Unit, Alma Mater Studiorum–University of Bologna, Bologna: Elton Dajti, Giovanni Marasco, Federico Ravaioli. Department of Specialist, Diagnostic and Experimental Medicine, Radiology Unit, University of Bologna: Alberta Cappelli, Rita Golfieri, Cristina Mosconi, Matteo Renzulli. Gastroenterology and Digestive Endoscopy Unit, Foggia University Hospital, Foggia: Ester Marina Cela, Antonio Facciorusso. Department of Internal Medicine, Gastroenterology Unit, University of Genova, IRCCS Policlinico San Martino, Genova: Valentina Cacciato, Edoardo Casagrande, Alessandro Moscatelli, Gaia Pellegatta. Gastroenterology Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Roma:Nicoletta de Matthaeis. Department of Gastroenterology, Polytechnic University of Marche, Ancona: Gloria Allegrini, Alessandro Di Bucchianico. Gastroenterology Unit, Belcolle hospital, Viterbo: Valentina Lauria, Giorgia Ghittoni, Giorgio Pelecca. Vascular and Interventional Radiology Unit, Belcolle hospital, Viterbo: Fabrizio Chegai, Fabio Coratella, Mariano Ortenzi. Department of Medicine and Surgery, Infectious Diseases and Hepatology Unit, University of Parma and Azienda Ospedaliero-Universitaria of Parma: Elisabetta Biasini, Andrea Olivani. Gastroenterology Unit, IRCCS Sacro Cuore Don Calabria hospital, Negrar: Alessandro Inno, Fabiana Marchetti. Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, PROMISE, Gastroenterology & Hepatology Unit, University of Palermo: Anita Busacca, Giuseppe Cabibbo, Calogero Cammà, Vincenzo Di Martino, Giacomo Emanuele Maria Rizzo. Department of Clinical and Experimental Medicine, Clinical and Molecular Hepatology Unit, University of Messina: Maria Stella Franzè, Carlo Saitta. Department of Medical, Surgical and Experimental Sciences, Azienda Ospedaliero-Universitaria of Sassari: Assunta Sauchella. Department of Internal Medicine, Ospedale per gli Infermi di Faenza: Vittoria Bevilacqua, Dante Berardinelli, Alberto Borghi, Andrea Casadei Gardini, Fabio Conti, Alessandro Cucchetti, Anna Chiara Dall’Aglio, Giorgio Ercolani. Department of Experimental and Clinical Medicine, Internal Medicine and Hepatology Unit, University of Firenze: Claudia Campani, Chiara Di Bonaventura, Stefano Gitto. Department of Clinical Medicine and Surgery, Hepato‐Gastroenterology Unit, University of Napoli "Federico II": Pietro Coccoli Antonio Malerba. Department of Clinical Medicine and Surgery, Gastroenterology Unit, University of Napoli "Federico II": Mario Capasso, Maria Guarino. Department of Clinical and Experimental Medicine, Hepatology and Liver Physiopathology Laboratory, University Hospital of Pisa, Pisa, Italy: Filippo Oliveri, Veronica Romagnoli.

      • Contributors Concept and design: AV, GS-B, LM and FF. Writing of article: AV, GS-B, GMa and FF. Statistical analysis: AV and GVDR. Patients enrolment and database construction: GS-B, AO, MC, EGG, FPi, GRap, MDM, EC, MZ, RS, GC, FM, AM, FM, AG, FGF, GMi, AM, GN, GR, FA, GV, FO, FPe, RRM, FT, UC, LM and FF. Study refinement, correction and approval: GS-B, AO, MC, EGG, FPi, GRap, MDM, EC, MZ, RS, GC, FM, AM, FM, AG, FGF, GMi, AM, GN, GR, FA, GV, FO, FPe, RRM, FT, UC, LM and FF. Guarantor: GS-B.

      • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

      • Competing interests None declared.

      • Provenance and peer review Not commissioned; externally peer reviewed.

      • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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