From "Burnt-Out" to "Burning-Out": Capturing Liver Fat Loss in Patients with Advanced Metabolic Dysfunction-Associated Steatotic Liver Disease from A Dynamic Perspective

Liu WY 1 , Huang S 2 , Ji H 3 , Kim SU 4 , Cheuk-Fung Yip T 5 , Lai-Hung Wong G 5 Show all authors , Petta S 6 , Tsochatzis E 7 , Nakajima A 8 , Bugianesi E 9 , George Goh BB 10 , Chan WK 11 , Romero-Gomez M 12 , Sanyal AJ 13 , Boursier J 14 , Hagström H 15 , Calleja JL 16 , de Lédinghen V 17 , Newsome PN 18 , Fan JG 19 , Lai M 20 , Castéra L 21 , Lee HW 4 , Pennisi G 6 , Yoneda M 8 , Armandi A 9 , Kim-Jun Teh K 10 , Gallego-Durán R 12 , Asgharpour A 13 , de Saint-Loup M 14 , Shang Y 22 , Llop E 16 , Fournier C 17 , Mahgoub S 18 , Lara-Romero C 12 , Canivet CM 14 , Sau-Wai Chan M 17 , Lin H 23 , Chen LL 24 , Targher G 25 , Byrne CD 26 , Du M 27 , Wai-Sun Wong V 28 , Zheng MH 29 , VCTE-Prognosis Study Group

Affiliations 

  • 1 Department of Endocrinology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China; Wenzhou Key Laboratory of Diabetes Research, Wenzhou, China
  • 2 Department of Infectious Disease, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
  • 3 Department of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
  • 4 Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
  • 5 Medical Data Analytics Centre, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China; State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
  • 6 Sezione di Gastroenterologia, Di.Bi.M.I.S., University of Palermo, Italy
  • 7 University College London Institute for Liver and Digestive Health, Royal Free Hospital, London, United Kingdom
  • 8 Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
  • 9 Department of Medical Sciences, Division of Gastroenterology and Hepatology, A.O. Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
  • 10 Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore
  • 11 Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Malaysia
  • 12 Digestive Diseases Unit and CIBERehd, Virgen Del Rocío University Hospital, Seville, Spain
  • 13 Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA, USA
  • 14 Hepato-Gastroenterology and Digestive Oncology Department, Angers University Hospital, Angers, France
  • 15 Department of Medicine, Huddinge, Karolinska Institutet, Sweden; Division of Hepatology, Department of Upper GI Diseases, Karolinska University Hospital, Stockholm, Sweden
  • 16 Department of Gastroenterology and Hepatology, Hospital Universitario Puerta de Hierro Majadahonda, Madrid
  • 17 Echosens, Paris, France
  • 18 Institute of Hepatology, Faculty of Life Sciences & Medicine, King's College London and King's College Hospital, London, UK
  • 19 Department of Gastroenterology and Hepatology, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
  • 20 Division of Gastroenterology & Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
  • 21 Université Paris Cité, UMR1149 (CRI), INSERM, Paris, France; Service d'Hépatologie, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris (AP-HP), Clichy, France
  • 22 Department of Medicine, Huddinge, Karolinska Institutet, Sweden
  • 23 Department of Gastroenterology and Hepatology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Center for Digestive Diseases Research and Clinical Translation of Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Gut Microecology and Associated Major Diseases Research, Shanghai, China
  • 24 MAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
  • 25 Department of Medicine, University of Verona, Verona, Italy; Metabolic Diseases Research Unit, IRCCS Sacro Cuore - Don Calabria Hospital, Negrar di Valpolicella, Italy
  • 26 Southampton National Institute for Health and Care Research Biomedical Research Centre, University Hospital Southampton, and University of Southampton, Southampton General Hospital, Southampton, UK
  • 27 Department of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China. Electronic address: drdumulong@njmu.edu.cn
  • 28 Medical Data Analytics Centre, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China; State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China; Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong, China. Electronic address: wongv@mect.cuhk.edu.hk
  • 29 MAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China; Institute of Hepatology, Wenzhou Medical University, Wenzhou, China; Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China. Electronic address: zhengmh@wmu.edu.cn
Gastroenterology, 2025 Mar 18.
PMID: 40113099 DOI: 10.1053/j.gastro.2025.02.034

Abstract

BACKGROUND & AIMS: The absence of hepatic fat in advanced fibrosis has been documented in metabolic dysfunction-associated steatotic liver disease (''burnt-out" MASLD). However, whether hepatic fat loss occurs continuously with fibrosis progression is controversial. We proposed a "burning-out" concept to describe this process and analyze the long-term outcomes of "burnt-out" and "burning-out" MASLD.

METHODS: We included a MASLD cohort from 16 centers, including 3273 individuals with baseline histology and 5455 with serial vibration-controlled transient elastography (VCTE) measurements during the follow-up. "Burnt-out" MASLD was defined by steatosis grade ≤ S1 and fibrosis stage ≥ F3. Trajectory analysis identified "burning-out" patients with continuous trends of decreasing controlled attenuation parameter (CAP) and increasing liver stiffness measurement (LSM) values.

RESULTS: Of 3273 patients with histological evaluation included, 435 had "burnt-out" MASLD. Compared to those with pronounced steatosis in advanced fibrosis, patients with "burnt-out" had higher risks of all-cause mortality (HR, 2.14; 95% CI, 1.14 to 4.02), liver-related events (LREs) (HR, 1.77; 95% CI, 1.12 to 2.78), and hepatic decompensation (HR, 1.83, 95% CI, 1.11 to 3.01). Of 5455 patients with VCTEs included for trajectory analysis, 176 were identified as "burning-out" MASLD. The incidence rates of all-cause mortality, LREs, and decompensation were 7.28, 26.47, and 21.92 per 1000 person-years in "burning-out" patients, respectively. The "burning-out" group had higher cumulative incidences of adverse outcomes than patients with consistently high CAP and moderate/low LSM values (P <0.0001).

CONCLUSION: Continuous hepatic fat loss accompanied by fibrosis progression, referred to as "burning-out", was observed in advanced MASLD and associated with high rates of all-cause mortality, LREs and hepatic decompensation.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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