Predictors of fibrosis, clinical events and mortality in MASLD: Data from the Global-MASLD study

Zobair M Younossi^{1

2}, Leyla de Avila^{1

2}, Salvatore Petta^{1

3}, Hannes Hagström^{1

4}, Seung Up Kim^{1

5}, Atsushi Nakajima^{1

6}, Javier Crespo^{1

7}, Laurent Castera^{1

8}, Naim Alkhouri^{1

9}, Ming-Hua Zheng^{1

10}, Sombat Treeprasertsuk^{1

11}, Prooksa Ananchuensook^{1

11}, Shalimar^{1

12}, Emmanuel Tsochatzis^{1

13}, Shenoy Kotacherry Trivikrama^{1

14}, Leena Kondarappassery Balakumaran^{1

15}, Jian-Gao Fan^{1

16}, Stuart K Roberts^{1

17}, Khalid Alswat^{1

18}, Vincent Wai-Sun Wong^{1

19}, Yusuf Yilmaz^{1

20}, Winston Dunn²¹, Sven Francque^{1

22}, Ahmed Cordie^{1

23}, Ming-Lung Yu^{1

24}, Mattias Ekstedt²⁵, George Boon-Bee Goh^{1

26}, Claudia P Oliveira^{1

27}, Mario Guimaraes Pessoa^{1

28}, Wah Kheong Chan^{1

29}, Marlen Ivon Castellanos Fernandez^{1

30}, Ajay Duseja^{1

31}, Juan Pablo Arab^{1

32}, George Papatheodoridis^{1

33}, Giada Sebastiani^{1

34}, Cristiane Villela-Nogueira^{1

35}, Roberta D'Ambrosio³⁶, Pietro Lampertico^{1

36}, Khalid Alnaamani^{1

37}, A G Holleboom^{1

38}, Arun Valsan^{1

39}, Arathi Venu³⁹, Mohamed El-Kassas^{1

40}, Grazia Pennisi³, Ying Shang⁴¹, Wen-Yue Liu¹⁰, Hye Won Lee⁵, Takashi Kobayashi⁶, Satoru Kakizaki^{1

42}, Cyrielle Caussy^{1

43}, Brian Pearlman^{1

44}, Paula Iruzubieta⁷, Rida Nadeem⁹, Felice Cinque³⁴, Antonia Neonaki³³, Mirko Zoncapé⁴⁵, Rui-Xu Yang¹⁶, Sherlot Juan Song¹⁹, Nicholas Dunn²¹, Zouhir Gadi²², Ming-Lun Yeh⁴⁶, Kevin Kim-Jun The²⁶, Sanjiv Mahadeva²⁹, Licet Gonzalez Fabian⁴⁷, Ahmed Almohsen⁴⁸, Nathalie Leite³⁵, Nicola Pugliese⁴⁹, Johan Vessby⁵⁰, Chencheng Xie⁵¹, Narendra Singh Choudhary⁵², Ethan Friend⁵³, Maria Poca⁵⁴, Takumi Kawaguchi^{1

55}, Francesco Paolo Russo⁵⁶, Adrian Gadano^{1

57}, Luis Antonio Diaz^{1

58}, Ashwani K Singal^{1

59}, Berenice Segrestin^{1

43}, Nadege Gunn^{1

53}, Didac Mauricio^{1

60}, Marco Arrese^{1

61}, Anna Fracanzani⁶², Brian Lam^{1

2}, Andrei Racila^{1

2}, Saleh A Alqahtani^{1

63}, Maria Stepanova^{1

2

64}; Global NASH/MASH Council (GNC)

Affiliations

¹ The Global NASH Council (GNC), Washington DC, United States.
² Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, VA, United States.
³ Section of Gastroenterology, PROMISE Department, University of Palermo, Palermo, Italy.
⁴ Division of Hepatology, Department of Upper GI Diseases, Karolinska University Hospital, Stockholm, Sweden.
⁵ Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea, Rep. of South.
⁶ Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
⁷ Gastroenterology and Hepatology Department, Clinical and Translational Research in Digestive Diseases, Valdecilla Research Institute (IDIVAL), Marques de Valdecilla University Hospital, Santander, Spain.
⁸ Department of Hepatology, Hospital Beaujon, Assistance Publique-Hôpitaux de Paris, Université Paris-Cité, Paris, France.
⁹ Arizona Liver Health, Chandler, United States.
¹⁰ Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
¹¹ Division of Gastroenterology, Department of Internal Medicine, Chulalongkorn University, Bangkok, Thailand.
¹² Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India.
¹³ University College London Institute for Liver and Digestive Health, Royal Free Hospital, London, United Kingdom.
¹⁴ Department of Gastroenterology, Sree Gokulam Medical College and Research Foundation, Kerala, India.
¹⁵ Population Health and Research Institute, Medical College P O, Trivandrum, India.
¹⁶ Department of Gastroenterology, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
¹⁷ Alfred Hospital Gastroenterology Department, Monash University, Melbourne, Australia.
¹⁸ Liver Disease Research Center, Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
¹⁹ Medical Data Analytics Center, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.
²⁰ Department of Gastroenterology, School of Medicine, Recep Tayyip Erdogan University, Istanbul, Türkiye.
²¹ Internal Medicine, Kansas University Medical Center, Kansas City, United States.
²² Department of Gastroenterology and Hepatology, Antwerp University Hospital, Edegem, Belgium.
²³ Cairo University Hospitals HIV Clinic, Endemic Medicine Department, Cairo University Hospitals, Cairo, Egypt.
²⁴ Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
²⁵ Department of Gastroenterology and Hepatology, Department of Health, Medicine, and Caring Sciences, Linköping University, Linköping, Sweden.
²⁶ Department of Gastroenterology & Hepatology, Singapore General Hospital, Singapore, Singapore.
²⁷ Department of Gastroenterology, Faculdade Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil.
²⁸ Hospital das Clínicas da Faculdade Medicina da Universidade de São Paulo, Sao Paulo, Brazil.
²⁹ Gastroenterology and Hepatology Unit, Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
³⁰ Department of Research and Teaching, Institute of Gastroenterology, University of Medical Sciences of Havana, Havana, Cuba.
³¹ Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
³² Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, United States.
³³ 1st Academic Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece.
³⁴ Division of Gastroenterology and Hepatology, Department of Medicine, McGill University Health Centre, Montreal, Canada.
³⁵ School of Medicine, Internal Medicine Department and Hepatology Division, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
³⁶ Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
³⁷ Division of Gastroenterology and Hepatology, Department of Medicine, The Medical City for Military and Security Services, Muscat, Oman.
³⁸ Department of Vascular Medicine, Amsterdam University Medical Center, Amsterdam, Netherlands.
³⁹ Centre for Metabolic Liver Disease and Integrated Liver Care Unit, Amrita Institute of Medical Sciences, Kochi, India.
⁴⁰ Endemic Medicine and Hepatology Department, Helwan University, Cairo, Egypt.
⁴¹ Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
⁴² Department of Clinical Research, NHO Takasaki General Medical Center, Takasaki, Japan.
⁴³ Département Endocrinologie, Diabète et Nutrition, Hôpital Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, Lyon, France.
⁴⁴ Department of Internal Medicine, Hamilton Medical Center, Medical College of Georgia, Dalton, United States.
⁴⁵ Liver Unit, Department of Internal Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.
⁴⁶ Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung, Taiwan.
⁴⁷ Department of Pathological Anatomy, Institute of Gastroenterology, University of Medical Sciences of Havana, Havana, Cuba.
⁴⁸ Department of Medicine, Schulich School of Medicine, Western University & London Health Sciences Centre, London, Ontario, Canada.
⁴⁹ Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.
⁵⁰ Department of Medical Sciences, Gastroenterology Research Group, Upssala University, Upssala, Sweden.
⁵¹ Division of Hepatology, Avera McKennan Hospital & University Health Center, Sioux Falls, United States.
⁵² Hepatology, and Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurugram, Haryana, India.
⁵³ Velocity Clinical Research, Waco, United States.
⁵⁴ Department of Gastroenterology, CIBEREHD, IR Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
⁵⁵ Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
⁵⁶ Department of Surgery, Oncology and Gastroenterology, University of Padova Gastroenterology Unit, Azienda Ospedaliera - Universita Padova, Padova, Italy.
⁵⁷ Liver Unit, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
⁵⁸ Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad.
⁵⁹ Católica de Chile, Santiago, Chile.XDepartment of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, University of Louisville, Louisville, United States.
⁶⁰ Department of Endocrinology & Nutrition, CIBERDEM, IR Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
⁶¹ Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
⁶² Department of Pathophysiology and Transplantation, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
⁶³ Liver, Digestive, and Lifestyle Health Research Section, and Organ Transplant Center of Excellence, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
⁶⁴ Center for Outcomes Research in Liver Disease, Washington, DC, United States.

PMID: 41231627
DOI: 10.1097/HEP.0000000000001617

Predictors of fibrosis, clinical events and mortality in MASLD: Data from the Global-MASLD study

Zobair M Younossi et al. Hepatology. 2025.

. 2025 Nov 13.

doi: 10.1097/HEP.0000000000001617. Online ahead of print.

Authors

Affiliations

¹ The Global NASH Council (GNC), Washington DC, United States.
² Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, VA, United States.
³ Section of Gastroenterology, PROMISE Department, University of Palermo, Palermo, Italy.
⁴ Division of Hepatology, Department of Upper GI Diseases, Karolinska University Hospital, Stockholm, Sweden.
⁵ Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea, Rep. of South.
⁶ Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
⁷ Gastroenterology and Hepatology Department, Clinical and Translational Research in Digestive Diseases, Valdecilla Research Institute (IDIVAL), Marques de Valdecilla University Hospital, Santander, Spain.
⁸ Department of Hepatology, Hospital Beaujon, Assistance Publique-Hôpitaux de Paris, Université Paris-Cité, Paris, France.
⁹ Arizona Liver Health, Chandler, United States.
¹⁰ Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
¹¹ Division of Gastroenterology, Department of Internal Medicine, Chulalongkorn University, Bangkok, Thailand.
¹² Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India.
¹³ University College London Institute for Liver and Digestive Health, Royal Free Hospital, London, United Kingdom.
¹⁴ Department of Gastroenterology, Sree Gokulam Medical College and Research Foundation, Kerala, India.
¹⁵ Population Health and Research Institute, Medical College P O, Trivandrum, India.
¹⁶ Department of Gastroenterology, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
¹⁷ Alfred Hospital Gastroenterology Department, Monash University, Melbourne, Australia.
¹⁸ Liver Disease Research Center, Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
¹⁹ Medical Data Analytics Center, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.
²⁰ Department of Gastroenterology, School of Medicine, Recep Tayyip Erdogan University, Istanbul, Türkiye.
²¹ Internal Medicine, Kansas University Medical Center, Kansas City, United States.
²² Department of Gastroenterology and Hepatology, Antwerp University Hospital, Edegem, Belgium.
²³ Cairo University Hospitals HIV Clinic, Endemic Medicine Department, Cairo University Hospitals, Cairo, Egypt.
²⁴ Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
²⁵ Department of Gastroenterology and Hepatology, Department of Health, Medicine, and Caring Sciences, Linköping University, Linköping, Sweden.
²⁶ Department of Gastroenterology & Hepatology, Singapore General Hospital, Singapore, Singapore.
²⁷ Department of Gastroenterology, Faculdade Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil.
²⁸ Hospital das Clínicas da Faculdade Medicina da Universidade de São Paulo, Sao Paulo, Brazil.
²⁹ Gastroenterology and Hepatology Unit, Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
³⁰ Department of Research and Teaching, Institute of Gastroenterology, University of Medical Sciences of Havana, Havana, Cuba.
³¹ Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
³² Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, United States.
³³ 1st Academic Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece.
³⁴ Division of Gastroenterology and Hepatology, Department of Medicine, McGill University Health Centre, Montreal, Canada.
³⁵ School of Medicine, Internal Medicine Department and Hepatology Division, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
³⁶ Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
³⁷ Division of Gastroenterology and Hepatology, Department of Medicine, The Medical City for Military and Security Services, Muscat, Oman.
³⁸ Department of Vascular Medicine, Amsterdam University Medical Center, Amsterdam, Netherlands.
³⁹ Centre for Metabolic Liver Disease and Integrated Liver Care Unit, Amrita Institute of Medical Sciences, Kochi, India.
⁴⁰ Endemic Medicine and Hepatology Department, Helwan University, Cairo, Egypt.
⁴¹ Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
⁴² Department of Clinical Research, NHO Takasaki General Medical Center, Takasaki, Japan.
⁴³ Département Endocrinologie, Diabète et Nutrition, Hôpital Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, Lyon, France.
⁴⁴ Department of Internal Medicine, Hamilton Medical Center, Medical College of Georgia, Dalton, United States.
⁴⁵ Liver Unit, Department of Internal Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.
⁴⁶ Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung, Taiwan.
⁴⁷ Department of Pathological Anatomy, Institute of Gastroenterology, University of Medical Sciences of Havana, Havana, Cuba.
⁴⁸ Department of Medicine, Schulich School of Medicine, Western University & London Health Sciences Centre, London, Ontario, Canada.
⁴⁹ Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.
⁵⁰ Department of Medical Sciences, Gastroenterology Research Group, Upssala University, Upssala, Sweden.
⁵¹ Division of Hepatology, Avera McKennan Hospital & University Health Center, Sioux Falls, United States.
⁵² Hepatology, and Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurugram, Haryana, India.
⁵³ Velocity Clinical Research, Waco, United States.
⁵⁴ Department of Gastroenterology, CIBEREHD, IR Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
⁵⁵ Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
⁵⁶ Department of Surgery, Oncology and Gastroenterology, University of Padova Gastroenterology Unit, Azienda Ospedaliera - Universita Padova, Padova, Italy.
⁵⁷ Liver Unit, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
⁵⁸ Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad.
⁵⁹ Católica de Chile, Santiago, Chile.XDepartment of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, University of Louisville, Louisville, United States.
⁶⁰ Department of Endocrinology & Nutrition, CIBERDEM, IR Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
⁶¹ Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
⁶² Department of Pathophysiology and Transplantation, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
⁶³ Liver, Digestive, and Lifestyle Health Research Section, and Organ Transplant Center of Excellence, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
⁶⁴ Center for Outcomes Research in Liver Disease, Washington, DC, United States.

PMID: 41231627
DOI: 10.1097/HEP.0000000000001617

Abstract

Background: Advanced histologic fibrosis is a major predictor of mortality in metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to identify advanced fibrosis clinical determinants across diverse MASLD populations and to assess the prognostic value of non-invasive markers (NITs) of fibrosis for adverse outcomes.

Methods: The Global MASLD (G-MASLD) enrolled biopsy-confirmed MASLD patients with clinical, histologic, and non-invasive test (NIT) data. Factors associated with the presence of advanced histologic fibrosis (F3-F4) in MASLD and clinical outcomes were assessed.

Results: There were 17,792 MASLD patients. Advanced fibrosis (≥F3) was present in 35%. The prevalence of type 2 diabetes (T2D) increased stepwise with fibrosis stage, from 28% in F0 to 70% in F4 (trend p<0.0001). Independent predictors of advanced fibrosis included older age, T2D, and obesity, although the association with obesity varied by region. Among patients with follow-up (mean 6.6 y), 6.5% died and 10.1% experienced a clinical event. Older age, male sex, T2D, and obesity were independent predictors of both mortality and clinical events (p<0.05). Fibrosis severity, whether defined histologically or by NITs, was strongly associated with higher risks of death and liver-related outcomes (all aHR>1.0, p<0.001). Five-year mortality was 2.1% overall, rising to 8.3% in patients with cirrhosis, and exceeded 10% among those with high-risk NIT score values.

Conclusions: In this large global biopsy-based MASLD cohort, advanced fibrosis was highly prevalent and strongly linked to T2D. Both histologic fibrosis and NITs were independent predictors of mortality and clinical outcomes, underscoring the prognostic value of fibrosis assessment with non-invasive tests.

Keywords: biomarkers; chronic liver disease; diagnostic thresholds; metabolic syndrome; non-communicable diseases; outcomes; steatohepatitis; steatotic liver disease.

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Predictors of fibrosis, clinical events and mortality in MASLD: Data from the Global-MASLD study

Affiliations

Predictors of fibrosis, clinical events and mortality in MASLD: Data from the Global-MASLD study

Authors

Affiliations

Abstract

LinkOut - more resources

Full Text Sources

Miscellaneous