Author information

¹Xi'an Medical University, Xi'an, China; Department of Infectious Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

²Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.

³Senior Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.

⁴Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and Thai Red Cross, Bangkok, Thailand.

⁵Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, Japan.

⁶Hepatology Unit, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian, China.

⁷UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK.

⁸Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.

⁹Department of Internal Medicine I, University Medical Centre of the Johannes Gutenberg-University Mainz, Mainz, Rhineland-Palatinate, Germany; Department of Medicine II, University Medical Center Homburg, Homburg and University of the Saarland, Saarbrücken, Germany.

¹⁰Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Malaysia.

¹¹Department of Hepatology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China.

¹²Centre d'Investigation de la Fibrose Hépatique, Hôpital Haut-Lévêque, Bordeaux University Hospital, Pessac, and INSERM U1312, Bordeaux University, Bordeaux, France.

¹³Sezione di Gastroenterologia, Di.Bi.M.I.S., University of Palermo, Italy.

¹⁴Department of Medical Sciences, Division of Gastroenterology and Hepatology, A.O. Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy.

¹⁵Department of Medicine, Huddinge, Karolinska Institutet, Sweden; Division of Hepatology, Department of Upper GI Diseases, Karolinska University Hospital, Huddinge, Stockholm, Sweden.

¹⁶Hepato-Gastroenterology and Digestive Oncology Department, Angers University Hospital, Angers, France; HIFIH Laboratory, SFR ICAT 4208, Angers University, Angers, France.

¹⁷Department of Gastroenterology and Hepatology, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain.

¹⁸Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore.

¹⁹Digestive Diseases Unit and CIBERehd, Virgen Del Rocío University Hospital, Seville, Spain.

²⁰Stravitz-Sanyal Institute of Liver Disease and Metabolic Health, Department of Internal Medicine, VCU School of Medicine, Richmond, VA, USA.

²¹Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai, China.

²²Université Paris Cité, UMR1149 (CRI), INSERM, Paris, France; Service d'Hépatologie, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris (AP-HP), Clichy, France.

²³Division of Gastroenterology & Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.

²⁴Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom; Pinnacle Clinical Research, San Antonio, Texas, USA.

²⁵Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea.

²⁶Department of Hepatology and Infection, Sir Run Run Shaw Hospital, Affiliated with School of Medicine, Zhejiang University, Hangzhou, China.

²⁷Centre for Obesity Research and Education, Department of Surgery, Monash University, Melbourne, Australia.

²⁸Department of Hepatology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, China.

²⁹Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Yokohama, Japan.

³⁰The Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China.

³¹Department of Medical Imaging, Iuliu Hatieganu, University of Medicine and Pharmacy, Regional Institute of Gastroenterology and Hepatology "Prof. Dr. Octavian Fodor", Cluj-Napoca, Romania.

³²Department of Gastroenterology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

³³Translational Gastroenterology Unit, University of Oxford, Oxford, UK.

³⁴Institute for the Study of Liver Diseases, The Third People's Hospital of Changzhou, Changzhou, Jiangsu Province, China.

³⁵National Institute for Health Research Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK.

³⁶National Institute for Health Research Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham, Birmingham, UK; Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK; Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.

³⁷Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.

³⁸Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, NSW, Australia.

³⁹Department of Hepatobiliary Pancreatic Surgery, Eighth Hospital Affiliated to SunYat-sen University, Futian, Guangdong Province, China.

⁴⁰Division of Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.

⁴¹Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China.

⁴²Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China.

⁴³Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

⁴⁴Department of Hepatology, Tianjin Second People's Hospital, Tianjin, China.

⁴⁵Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.

⁴⁶Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang, China.

⁴⁷Clinical Laboratory Center, The Fifth People's Hospital of Wuxi, Wuxi, Jiangsu, China.

⁴⁸Department of Traditional and Western Medical Hepatology, Hebei Medical University Third Hospital, Shijiazhuang, China.

⁴⁹Department of Hepatology, Center of Infectious Diseases and Pathogen Biology, The First Hospital of Jilin University, Changchun, China.

⁵⁰Department of Infectious Diseases, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.

⁵¹Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China.

⁵²Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.

⁵³Department of lnfectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

⁵⁴Department of Hepatology of The Third Central Hospital of Tianjin, Tianjin, China.

⁵⁵Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

⁵⁶Department of lnfectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

⁵⁷Department of Hepatobiliary Diseases, Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan Province, China.

⁵⁸Center of Hepatology, Beijing Ditan Hospital, Capital Medical University, Beijing, China.

⁵⁹Medical 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.

⁶⁰Echosens, Paris, France.

⁶¹Department of Endocrinology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

⁶²Department of Medicine, Huddinge, Karolinska Institutet, Sweden.

⁶³Hepato-Gastroenterology and Digestive Oncology Department, Angers University Hospital, Angers, France.

⁶⁴National Institute for Health Research, Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham, Birmingham, United Kingdom.

⁶⁵Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

⁶⁶Department of Infectious Diseases, Qingdao Municipal Hospital Affiliated to Qingdao University, Qingdao, China.

⁶⁷Department of Gastroenterology, Southwest Hospital, Army Medical University, Chongqing, China.

⁶⁸Department of Metabolic and Bariatric Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China.

⁶⁹Department of Medicine, University of Verona, Verona, Italy; Metabolic Diseases Research Unit, IRCCS Sacro Cuore - Don Calabria Hospital, Negrar di Valpolicella, Italy.

⁷⁰Southampton National Institute for Health and Care Research Biomedical Research Centre, University Hospital Southampton and University of Southampton, Southampton General Hospital, Southampton, UK.

⁷¹Department of Gastroenterology, The First Affiliated Hospital of Xi'an Medical University, Xi'an, China.

⁷²Xi'an Medical University, Xi'an, China.

⁷³Department of Infectious Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

⁷⁴Medical 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. Electronic address: wongv@cuhk.edu.hk.

⁷⁵Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, Oxford, UK. Electronic address: michael.pavlides@cardiov.ox.ac.uk.

⁷⁶MAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China; Key Laboratory of Diagnosis and Treatment for The Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, Zhejiang, China. Electronic address: zhengmh@wmu.edu.cn.

Abstract

Background & aims: Metabolic dysfunction-associated steatohepatitis (MASH) and fibrotic MASH are significant health challenges. This multi-national study aimed to validate the acMASH index (including serum creatinine and aspartate aminotransferase concentrations) for MASH diagnosis and develop a new index (acFibroMASH) for non-invasively identifying fibrotic MASH and exploring its predictive value for liver-related events (LREs).

Methods: We analyzed data from 3,004 individuals with biopsy-proven metabolic dysfunction-associated fatty liver disease (MAFLD) across 29 Chinese and nine international cohorts to validate the acMASH index and develop the acFibroMASH index. Additionally, we utilized the independent external data from a multi-national cohort of 9,034 patients with MAFLD to examine associations between the acFibroMASH index and the risk of LREs.

Results: In the pooled global cohort, the acMASH index identified MASH with an AUROC of 0.802 (95%CI 0.786-0.818). The acFibroMASH index (including the acMASH index plus liver stiffness measurement) accurately identified fibrotic MASH with an AUROC of 0.808 in the derivation cohort and 0.800 in the validation cohort. Notably, the AUROC for the acFibroMASH index was 0.835 (95% CI 0.786-0.882), superior to that of the FAST score at 0.750 (95% CI 0.693-0.800, P<0.01) in predicting the 5-year risk of LREs. Patients with acFibroMASH >0.39 had a higher risk of LREs than those with acFibroMASH <0.15 (adjusted-hazard ratio: 11.23 95%CI 3.98-31.66).

Conclusions: This multi-ethnic study validates the acMASH index as a reliable, non-invasive test for identifying MASH. The newly proposed acFibroMASH index is a reliable test for identifying fibrotic MASH and predicting the risk of LREs.