{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:08:00Z","timestamp":1790784480202,"version":"4.1.0"},"reference-count":58,"publisher":"American Medical Association (AMA)","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA"],"abstract":"\n Importance<\/jats:title>\n Although metabolic dysfunction\u2013associated steatotic liver disease (MASLD) is traditionally associated with obesity, it is increasingly recognized in individuals with normal weight (ie, lean MASLD).<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To characterize the clinical, histologic, and prognostic features of lean MASLD, and evaluate the performance of noninvasive tests for advanced fibrosis.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n Multinational, retrospective observational study of adults with biopsy-confirmed MASLD from 41 countries from the Global MASLD project.<\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n Lean vs overweight\/obese MASLD, defined by body mass index (BMI) and waist circumference.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Primary outcomes were all-cause mortality and clinical events (hepatocellular carcinoma, hepatic decompensation, liver transplant, death), intermediate outcomes included histologic fibrosis severity, and tests included the Fibrosis-4 (FIB-4) score and liver stiffness measurement (LSM) by transient elastography.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Among 18\u202f326 patients (mean [SD] age, 50.9 [13.1] years; 8714 [47.6%] male), 6.7% were lean by BMI. Among 12\u202f202 patients with waist circumference available, 6.0% were lean by waist circumference (\u03ba\u2009=\u20090.41). Lean MASLD was most prevalent in Asia (11.3% by BMI, 11.7% by waist circumference). Compared with overweight\/obese MASLD, lean MASLD had lower prevalence of type 2 diabetes (38.2% vs 48.3%; difference, \u221210.2% [95% CI, \u221213.0% to \u22127.4%]), advanced fibrosis (29.3% vs 37.2%; difference, \u22127.8% [95% CI, \u221210.5% to \u22125.2%]), and Non-Alcoholic Fatty Liver Disease Activity Scores (mean [SD], 3.96 [1.81] vs 4.41 [1.68]; difference, \u22120.44 [95% CI, \u22120.56 to \u22120.33]). The FIB-4 demonstrated lower accuracy for predicting advanced fibrosis (F3-F4) in lean vs overweight\/obese MASLD (area under the curve, 0.76 [95% CI, 0.73-0.79] vs 0.79 [95% CI, 0.78-0.80]; difference, \u22120.03 [95% CI, \u22120.06 to 0.00]), while LSM had higher accuracy (area under the curve, 0.87 [95% CI, 0.84-0.90] vs 0.83 [95% CI, 0.82-0.84]; difference, 0.04 [95% CI, 0.01-0.07]). Unadjusted rates per 100 person-years in lean vs overweight\/obese MASLD were 1.08 vs 0.91 for all-cause mortality and 1.51 vs 1.43 for clinical events, respectively; lean status was not independently associated with all-cause mortality (adjusted hazard ratio [aHR], 0.90 [95% CI, 0.69-1.16]) or clinical events (aHR, 0.94 [95% CI, 0.76-1.17]). Advanced fibrosis (F3-F4) was associated with all-cause mortality (1.46 vs 0.77 per 100 person-years; aHR, 2.10 [95% CI, 1.71-2.57]) and clinical events (3.21 vs 0.89 per 100 person-years; aHR, 3.41 [95% CI, 2.90-4.03]).<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n Lean MASLD represents a distinct phenotype with milder histologic disease but similar clinical outcomes compared with overweight\/obese MASLD. Fibrosis severity, rather than body composition, was associated with prognosis and LSM was reliable in lean individuals.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jama.2026.18491","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T15:32:28Z","timestamp":1790782348000},"source":"Crossref","is-referenced-by-count":0,"title":["Histologic Features and Clinical Outcomes of Lean Metabolic Dysfunction\u2013Associated Steatotic Liver Disease"],"prefix":"10.1001","author":[{"given":"Leyla","family":"de Avila","sequence":"first","affiliation":[{"name":"The Global NASH\/MASH Council (GNC), Washington, DC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid M.","family":"AlNaamani","sequence":"additional","affiliation":[{"name":"The Global NASH\/MASH Council (GNC), Washington, DC"},{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, The Medical City for Military and Security Services, Muscat, Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita","family":"Papatheodoridi","sequence":"additional","affiliation":[{"name":"The Global NASH\/MASH Council (GNC), Washington, DC"},{"name":"1st Academic Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital of Athens, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Petta","sequence":"additional","affiliation":[{"name":"The Global NASH\/MASH Council (GNC), Washington, DC"},{"name":"Section of Gastroenterology, ProMISE Department, University of Palermo, Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannes","family":"Hagstr\u00f6m","sequence":"additional","affiliation":[{"name":"The Global NASH\/MASH Council (GNC), Washington, DC"},{"name":"Division of Hepatology, Department of Upper GI Diseases, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Up","family":"Kim","sequence":"additional","affiliation":[{"name":"The Global NASH\/MASH Council (GNC), Washington, DC"},{"name":"Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Nakajima","sequence":"additional","affiliation":[{"name":"The Global NASH\/MASH Council (GNC), Washington, DC"},{"name":"Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Crespo","sequence":"additional","affiliation":[{"name":"The Global NASH\/MASH Council (GNC), Washington, DC"},{"name":"Gastroenterology and Hepatology Department, Clinical and Translational Research in Digestive Diseases, Valdecilla Research Institute (IDIVAL), Marqu\u00e9s de Valdecilla University Hospital, Santander, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Castera","sequence":"additional","affiliation":[{"name":"The Global NASH\/MASH Council (GNC), Washington, DC"},{"name":"Department of Hepatology, Hospital Beaujon, Assistance Publique-H\u00f4pitaux de Paris, Universit\u00e9 Paris-Cit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naim","family":"Alkhouri","sequence":"additional","affiliation":[{"name":"The Global NASH\/MASH Council (GNC), Washington, DC"},{"name":"Summit Clinical Research, San Antonio, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Hua","family":"Zheng","sequence":"additional","affiliation":[{"name":"The Global NASH\/MASH Council (GNC), Washington, DC"},{"name":"MAFLD Research Center, Department of Hepatology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sombat","family":"Treeprasertsuk","sequence":"additional","affiliation":[{"name":"The Global NASH\/MASH Council (GNC), Washington, DC"},{"name":"Division of Gastroenterology, Department of Internal Medicine, Chulalongkorn University, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Shalimar","sequence":"additional","affiliation":[{"name":"The Global NASH\/MASH Council (GNC), Washington, DC"},{"name":"Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Tsochatzis","sequence":"additional","affiliation":[{"name":"The Global NASH\/MASH Council (GNC), Washington, DC"},{"name":"University College London Institute for Liver and Digestive Health, Royal Free Hospital, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenoy Kotacherry","family":"Trivikrama","sequence":"additional","affiliation":[{"name":"The Global NASH\/MASH Council (GNC), Washington, DC"},{"name":"Department of Gastroenterology, Sree Gokulam Medical College & Research Foundation, Trivandrum, Kerala, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Gao","family":"Fan","sequence":"additional","affiliation":[{"name":"The Global NASH\/MASH Council (GNC), Washington, DC"},{"name":"Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart K.","family":"Roberts","sequence":"additional","affiliation":[{"name":"The Global NASH\/MASH Council (GNC), Washington, DC"},{"name":"Alfred Hospital Gastroenterology Department, Monash University, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid","family":"Alswat","sequence":"additional","affiliation":[{"name":"The Global NASH\/MASH Council (GNC), Washington, DC"},{"name":"Liver Disease Research Center, Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent Wai-Sun","family":"Wong","sequence":"additional","affiliation":[{"name":"The Global NASH\/MASH Council (GNC), Washington, DC"},{"name":"Medical Data Analytics Center, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuf","family":"Yilmaz","sequence":"additional","affiliation":[{"name":"The Global NASH\/MASH Council (GNC), Washington, DC"},{"name":"Department of Gastroenterology, School of Medicine, Recep Tayyip Erdo\u011fan University, Rize, 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Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"D\u2019Ambrosio","sequence":"additional","affiliation":[{"name":"The Global NASH\/MASH Council (GNC), Washington, DC"},{"name":"Division of Gastroenterology and Hepatology, Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Lampertico","sequence":"additional","affiliation":[{"name":"The Global NASH\/MASH Council (GNC), Washington, DC"},{"name":"Division of Gastroenterology and Hepatology, Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. G.","family":"Holleboom","sequence":"additional","affiliation":[{"name":"The Global NASH\/MASH Council (GNC), Washington, DC"},{"name":"Department of Vascular Medicine, Amsterdam University Medical Center, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun","family":"Valsan","sequence":"additional","affiliation":[{"name":"The Global NASH\/MASH Council (GNC), Washington, DC"},{"name":"Centre for Metabolic Liver Disease and Integrated Liver Care Unit, Amrita Institute of Medical Sciences, Kochi, Kerala, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"El-Kassas","sequence":"additional","affiliation":[{"name":"The Global NASH\/MASH Council (GNC), Washington, DC"},{"name":"Endemic Medicine Department, Faculty of Medicine, Capital University (formerly Helwan University), Cairo, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"The Global NASH\/MASH Council (GNC), Washington, DC"},{"name":"Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Kakizaki","sequence":"additional","affiliation":[{"name":"The Global NASH\/MASH Council (GNC), Washington, DC"},{"name":"Department of Clinical Research, NHO Takasaki General Medical Center, Takasaki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyrielle","family":"Caussy","sequence":"additional","affiliation":[{"name":"The Global NASH\/MASH Council (GNC), Washington, DC"},{"name":"D\u00e9partement Endocrinologie, Diab\u00e8te et Nutrition, H\u00f4pital Lyon Sud, Hospices Civils de Lyon, Pierre-B\u00e9nite, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Pearlman","sequence":"additional","affiliation":[{"name":"The Global NASH\/MASH Council (GNC), Washington, DC"},{"name":"Department of Graduate Medical Education, Hamilton Medical Center, Medical College of Georgia, Dalton"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Pugliese","sequence":"additional","affiliation":[{"name":"The Global NASH\/MASH Council (GNC), Washington, DC"},{"name":"Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Vessby","sequence":"additional","affiliation":[{"name":"The Global NASH\/MASH Council (GNC), Washington, DC"},{"name":"Department of Medical Sciences, Gastroenterology Research Group, Uppsala University, Uppsala, 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