{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T22:49:07Z","timestamp":1794005347660,"version":"4.8.0"},"reference-count":28,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T00:00:00Z","timestamp":1748390400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background and aims: Metabolic dysfunction-associated steatotic liver disease (MASLD)-related hepatocellular carcinoma (HCC) may have distinct biological characteristics influencing systemic treatment response. However, the prognostic impact of MASLD vs. alcohol-related HCC in patients receiving lenvatinib remains unclear. This study aimed to assess lenvatinib\u2019s effectiveness and safety in these populations. Methods: A multicenter cohort of 378 HCC patients treated with lenvatinib (2019\u20132024) was analyzed. Propensity score matching was performed based on age, sex, tumoral stage, alpha-fetoprotein levels and Child\u2013Pugh class. Survival was estimated using Kaplan\u2013Meier analysis and compared with the log-rank test. Results were expressed as HR and 95% CI. Results: After matching, 115 patients per group were compared. Median OS was 21 months (95% CI: 20\u201323) in the group with metabolic dysfunction-associated steatohepatitis (MASH) and 19 months (95% CI: 18\u201321) in the group with alcohol etiology (p = 0.18). In multivariate analysis, only Child\u2013Pugh class (HR 2.67, 95% CI: 1.84\u20135.41) and tumor stage (HR 2.18, 95% CI: 1.57\u20136.93) resulted as significant predictors of OS. Median PFS was 9 months (95% CI: 8\u20139) in patients with MASH and 9 months (95% CI: 7\u201310) in patients with alcohol etiology (p = 0.33). Only the Child\u2013Pugh class was a significant predictor of PFS in univariate analysis (HR 1.56, 95% CI: 1.15\u20133.41; p = 0.03). No difference in terms of adverse event rate was observed between the two groups. Conclusions: Lenvatinib is effective in patients with both MASH- and alcohol-related HCC, with no difference in oncological outcomes between the two groups.<\/jats:p>","DOI":"10.3390\/cancers17111808","type":"journal-article","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T10:21:13Z","timestamp":1748427673000},"page":"1808","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Lenvatinib Is Highly Effective in Patients with Hepatocellular Carcinoma Related to Both Metabolic Dysfunction-Associated Steatohepatitis and Alcoholic Etiology: A Propensity Score Analysis"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9887-7315","authenticated-orcid":false,"given":"Rodolfo","family":"Sacco","sequence":"first","affiliation":[{"name":"Gastroenterology and Digestive Endoscopy Unit, Department of Surgical and Medical Sciences, University of Foggia, Viale Pinto 1, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8526-837X","authenticated-orcid":false,"given":"Edoardo G.","family":"Giannini","sequence":"additional","affiliation":[{"name":"Gastroenterology Unit, Department of Internal Medicine, University of Genova, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale Policlinico San Martino, 16126 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaella","family":"Tortora","sequence":"additional","affiliation":[{"name":"Liver Unit, Department of Transplantation, Cardarelli Hospital, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovan Giuseppe","family":"Di Costanzo","sequence":"additional","affiliation":[{"name":"Liver Unit, Department of Transplantation, Cardarelli Hospital, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0458-3763","authenticated-orcid":false,"given":"Andrea","family":"Mega","sequence":"additional","affiliation":[{"name":"Gastroenterology Unit, Bolzano Regional Hospital, 39100 Bolzano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8239-395X","authenticated-orcid":false,"given":"Luca","family":"Marzi","sequence":"additional","affiliation":[{"name":"Gastroenterology Unit, Bolzano Regional Hospital, 39100 Bolzano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Pieri","sequence":"additional","affiliation":[{"name":"Gastroenterology Unit, Department of Internal Medicine, University of Genova, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale Policlinico San Martino, 16126 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1791-4506","authenticated-orcid":false,"given":"Andrea","family":"Pasta","sequence":"additional","affiliation":[{"name":"Gastroenterology Unit, Department of Internal Medicine, University of Genova, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale Policlinico San Martino, 16126 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2638-3156","authenticated-orcid":false,"given":"Bruno","family":"Daniele","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, Ospedale del Mare, 80147 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0863-7546","authenticated-orcid":false,"given":"Piera","family":"Federico","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, Ospedale del Mare, 80147 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0946-3859","authenticated-orcid":false,"given":"Giuseppe","family":"Cabibbo","sequence":"additional","affiliation":[{"name":"Section of Gastroenterology & Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Russello","sequence":"additional","affiliation":[{"name":"Liver Unit, ARNAS Garibaldi-Nesima, 95122 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Cocuzza","sequence":"additional","affiliation":[{"name":"Liver Unit, ARNAS Garibaldi-Nesima, 95122 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Giacomelli","sequence":"additional","affiliation":[{"name":"Polistudium SRL, 20121 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6189-0578","authenticated-orcid":false,"given":"Marianna","family":"Silletta","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8292-1134","authenticated-orcid":false,"given":"Paolo","family":"Gallo","sequence":"additional","affiliation":[{"name":"Clinical Medicine and Hepatology Unit, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umberto Vespasiani","family":"Gentilucci","sequence":"additional","affiliation":[{"name":"Clinical Medicine and Hepatology Unit, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Casadei-Gardini","sequence":"additional","affiliation":[{"name":"Department of Oncology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute Hospital, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernesto","family":"Claar","sequence":"additional","affiliation":[{"name":"Department of Medicine, Ospedale Evangelico Villa Betania, 80147 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5845-6703","authenticated-orcid":false,"given":"Adriano","family":"Pellicelli","sequence":"additional","affiliation":[{"name":"Liver Unit, Department of Liver Transplant, A.O. San Camillo Forlanini, 00152 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6387-6443","authenticated-orcid":false,"given":"Massimo","family":"Bellini","sequence":"additional","affiliation":[{"name":"Gastroenterology Unit, University of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9059-8311","authenticated-orcid":false,"given":"Filomena","family":"Morisco","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Concetta","family":"Tatali","sequence":"additional","affiliation":[{"name":"Gastroenterology and Digestive Endoscopy Unit, Department of Surgical and Medical Sciences, University of Foggia, Viale Pinto 1, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Pace Palitti","sequence":"additional","affiliation":[{"name":"Internal Medicine and Hepatology Unit, ASL Pescara, 65124 Pescara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Izzi","sequence":"additional","affiliation":[{"name":"Emergency and Highly Contagious Infectious Diseases, A.O. dei Colli, P.O.D. Cotugno, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Di Stefano","sequence":"additional","affiliation":[{"name":"Hepatology Unit, Umberto I Hospital, 00161 Siracusa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6541-3821","authenticated-orcid":false,"given":"Luca","family":"Rinaldi","sequence":"additional","affiliation":[{"name":"Department of Medicine and Health Sciences, University of Molise, 86100 Campobasso, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2107-2156","authenticated-orcid":false,"given":"Antonio","family":"Facciorusso","sequence":"additional","affiliation":[{"name":"Gastroenterology Unit, Department of Experimental Medicine, Universit\u00e0 del Salento, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1056\/NEJMra1001683","article-title":"Hepatocellular carcinoma","volume":"365","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1002\/hep.29086","article-title":"AASLD guidelines for the treatment of hepato-cellular carcinoma","volume":"67","author":"Heimbach","year":"2018","journal-title":"Hepatology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1056\/NEJMoa0708857","article-title":"Sorafenib in advanced hepatocellular carcinoma","volume":"359","author":"Llovet","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1111\/liv.13052","article-title":"Inducing tolerability of adverse events increases sorafenib exposure and optimizes patient\u2019s outcome in advanced hepatocellular carcinoma","volume":"36","author":"Ponziani","year":"2015","journal-title":"Liver Int."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1016\/S0140-6736(18)30207-1","article-title":"Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: A randomised phase 3 non-inferiority trial","volume":"391","author":"Kudo","year":"2018","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1894","DOI":"10.1056\/NEJMoa1915745","article-title":"Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma","volume":"382","author":"Finn","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1159\/000525145","article-title":"Real Life Study of Lenvatinib Therapy for Hepatocellular Carcinoma: RELEVANT Study","volume":"11","author":"Rimini","year":"2022","journal-title":"Liver Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2216","DOI":"10.21037\/jgo-24-351","article-title":"Real-world experience of lenvatinib-based therapy in patients with advanced hepatocellular carcinoma","volume":"15","author":"Wang","year":"2024","journal-title":"J. Gastrointest. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4760","DOI":"10.1158\/1078-0432.CCR-23-1462","article-title":"A Prospective Study Exploring the Safety and Efficacy of Lenvatinib for Patients with Advanced Hepatocellular Carcinoma and High Tumor Burden: The LAUNCH Study","volume":"29","author":"Kobayashi","year":"2023","journal-title":"Clin. Cancer Res."},{"key":"ref_10","first-page":"2379","article-title":"Lenvatinib versus sorafenib as first-line therapy of advanced hepatocellular carcinoma: A systematic review and meta-analysis","volume":"13","author":"Facciorusso","year":"2021","journal-title":"Am. J. Transl. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1159\/000530028","article-title":"Comparison between Atezolizumab Plus Bevacizumab and Lenvatinib for Hepatocellular Carcinoma in Patients with Child-Pugh Class B in Real-World Clinical Settings","volume":"101","author":"Ohama","year":"2023","journal-title":"Oncology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1111\/jgh.16225","article-title":"Impact of first-line systemic therapy with atezolizumab plus bevacizumab in patients with hepatocellular carcinoma","volume":"38","author":"Tada","year":"2023","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1159\/000533991","article-title":"Safety and Efficacy of Atezolizumab\/Bevacizumab in Patients with Hepatocellular Carcinoma and Impaired Liver Function: A Systematic Review and Meta-Analysis","volume":"13","author":"Pasta","year":"2023","journal-title":"Liver Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1111\/liv.15885","article-title":"Impact of body mass index on the prognosis of unresectable HCC patients receiving first-line Lenvatinib or atezolizumab plus bevacizumab","volume":"44","author":"Rimini","year":"2024","journal-title":"Liver Int."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Goh, M.J., Kang, W., Jeong, W.K., Sinn, D.H., Gwak, G.-Y., Paik, Y.-H., Choi, M.S., Lee, J.H., Koh, K.C., and Paik, S.W. (2022). Prognostic significance of cachexia index in patients with advanced hepatocellular carcinoma treated with systemic chemotherapy. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-11736-1"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Sacco, R., Ramai, D., Tortora, R., di Costanzo, G.G., Burlone, M.E., Pirisi, M., Federico, P., Daniele, B., Silletta, M., and Gallo, P. (2023). Role of Etiology in Hepatocellular Carcinoma Patients Treated with Lenvatinib: A Counterfactual Event-Based Mediation Analysis. Cancers, 15.","DOI":"10.3390\/cancers15020381"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Abd El Aziz, M.A., Facciorusso, A., Nayfeh, T., Saadi, S., Elnaggar, M., Cotsoglou, C., and Sacco, R. (2020). Immune checkpoint inhibitors for unre-sectable hepatocellular carcinoma. Vaccines, 8.","DOI":"10.3390\/vaccines8040616"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1038\/s41586-021-03362-0","article-title":"NASH limits anti-tumor surveillance in immunotherapy-treated HCC","volume":"592","author":"Pfister","year":"2021","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"100330","DOI":"10.1016\/j.esmoop.2021.100330","article-title":"Nonalcoholic steatohepatitis in hepatocarcinoma: New insights about its prognostic role in patients treated with lenvatinib","volume":"6","author":"Rimini","year":"2021","journal-title":"ESMO Open"},{"key":"ref_20","unstructured":"European Association for the Study of the Liver (2018). EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J. Hepatol., 69, 182\u2013236."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.jhep.2019.09.026","article-title":"mRECIST for HCC: Performance and novel refinements","volume":"72","author":"Llovet","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_22","unstructured":"(2025, April 05). Available online: https:\/\/ctep.cancer.gov\/protocoldevelopment\/electronic_applications\/docs\/ctcae_v5_quick_reference_5x7.pdf."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1002\/sim.3150","article-title":"A critical appraisal of propensity-score matching in the medical literature between 1996 and 2003","volume":"27","author":"Austin","year":"2007","journal-title":"Stat. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1080\/00273171.2011.568786","article-title":"An Introduction to Propensity Score Methods for Reducing the Effects of Confounding in Observational Studies","volume":"46","author":"Austin","year":"2011","journal-title":"Multivar. Behav. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1055\/a-2219-3179","article-title":"Lumen-apposing metal stents for the treatment of pancreatic and peripancreatic fluid collections and bleeding risk: A propensity matched study","volume":"56","author":"Mangiavillano","year":"2024","journal-title":"Endoscopy"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1097\/HEP.0000000000000520","article-title":"A multi-society Delphi consensus statement on new fatty liver disease nomenclature","volume":"78","author":"Rinella","year":"2023","journal-title":"Hepatology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/S2468-1253(22)00062-0","article-title":"Global multi-stakeholder endorsement of the MAFLD definition","volume":"7","author":"Bugianesi","year":"2022","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Kohya, R., Suda, G., Ohara, M., Sasaki, T., Yoda, T., Sakurai, N., Yoshida, S., Fu, Q., Yang, Z., and Hosoda, S. (2023). Potential Correlation between Changes in Serum FGF21 Levels and Lenvatinib-Induced Appetite Loss in Patients with Unresectable Hepatocellular Carcinoma. Cancers, 15.","DOI":"10.3390\/cancers15123257"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/11\/1808\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:42:31Z","timestamp":1760031751000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/11\/1808"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,28]]},"references-count":28,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["cancers17111808"],"URL":"https:\/\/doi.org\/10.3390\/cancers17111808","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,28]]}}}