{
  "abstract": "Background Current guidelines recommend a two-step approach for risk stratification of metabolic dysfunction-associated steatotic liver disease (MASLD), starting with Fibrosis-4 index (FIB-4) followed by liver stiffness measurement (LSM) using vibration-controlled transient elastography (VCTE).Objective To evaluate this approach for predicting advanced fibrosis and liver-related events (LREs) in patients with type 2 diabetes (T2D).Design A prospective liver biopsy cohort of T2D patients with histologically confirmed MASLD from seven centres in China was used to assess diagnostic performance for advanced fibrosis. The international VCTE-Prognosis cohort, including T2D patients with MASLD who underwent VCTE at 16 centres in the USA, Europe and Asia, with longitudinal follow-up, was used to assess LREs, defined as hepatic decompensation or hepatocellular carcinoma.Results 4781 participants were included. In the liver biopsy cohort (n=352; 22.2% with advanced fibrosis), applying LSM thresholds of <8 kPa and >12 kPa after FIB-4 classified patients into 63.4% low-risk, 9.4% intermediate-risk and 27.3% high-risk, with a correct classification rate of 71%. In the VCTE-Prognosis cohort (n=4429; median follow-up 51.3 (IQR 27.4–70.7) months), 140 (3.2%) patients developed LREs (110 (2.5%) with hepatic decompensation and 59 (1.3%) with hepatocellular carcinoma). The two-step approach classified 72.6%, 6.8% and 20.6% of patients into low-risk, intermediate-risk and high-risk groups, with corresponding 5-year cumulative LRE incidences of 0.7%, 0.9% and 11.8%. Refining classification of intermediate FIB-4 patients using LSM <10 kPa (low-risk) and >15 kPa (high-risk) reduced the intermediate-risk group to 5.6% while preserving predictive accuracy.Conclusion The non-invasive two-step approach of FIB-4 followed by LSM effectively stratifies MASLD-related advanced fibrosis and LREs risk in T2D. Applying LSM cut-offs of 10 and 15 kPa further optimises risk stratification for future LREs.",
  "authors": [
    {
      "affiliations": [
        "Liver Disease Center of Integrated Traditional Chinese and Western Medicine, Department of Radiology, Zhongda Hospital, Medical School, Southeast University",
        "Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Nanjing, China",
        "Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University",
        "State Key Laboratory of Digital Medical Engineering, Nanjing, China"
      ],
      "name": "Yuping Chen"
    },
    {
      "affiliations": [
        "Department of Ultrasound, The First Affiliated Hospital of Anhui Medical University, Hefei, China"
      ],
      "name": "Bingtian Dong"
    },
    {
      "affiliations": [
        "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"
      ],
      "name": "Xinrui Jin"
    },
    {
      "affiliations": [
        "Liver Disease Center of Integrated Traditional Chinese and Western Medicine, Department of Radiology, Zhongda Hospital, Medical School, Southeast University",
        "Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Nanjing, China",
        "Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University",
        "State Key Laboratory of Digital Medical Engineering, Nanjing, China"
      ],
      "name": "Chuan Liu"
    },
    {
      "affiliations": [
        "MAFLD Research Center, Department of Hepatology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China"
      ],
      "name": "Ming-Hua Zheng"
    },
    {
      "affiliations": [
        "Zhejiang Key Laboratory of Multi-omics Precision Diagnosis and Treatment of Liver Diseases, Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China"
      ],
      "name": "Xiao Liang"
    },
    {
      "affiliations": [
        "Liver Research Center, Beijing Friendship Hospital, Capital Medical University, State Key Lab of Digestive Health, National Clinical Research Center of Digestive Diseases, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, Beijing, China"
      ],
      "name": "Yameng Sun"
    },
    {
      "affiliations": [
        "Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea"
      ],
      "name": "Hye Won Lee"
    },
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Huapeng Lin"
    },
    {
      "affiliations": [
        "University College London Institute for Liver and Digestive Health, University College London and Royal Free Hospital, London, UK"
      ],
      "name": "Emmanuel Tsochatzis"
    },
    {
      "affiliations": [
        "Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine, and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy"
      ],
      "name": "Salvatore Petta"
    },
    {
      "affiliations": [
        "Department of Medical Sciences, Division of Gastroenterology, A.O.U. Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy"
      ],
      "name": "Elisabetta Bugianesi"
    },
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan"
      ],
      "name": "Masato Yoneda"
    },
    {
      "affiliations": [
        "Department of Medicine, Karolinska Institutet, Huddinge, Sweden",
        "Division of Hepatology, Department of Upper Gastrointestinal Diseases, Karolinska University Hospital, Huddinge, Stockholm, Sweden"
      ],
      "name": "Hannes Hagström"
    },
    {
      "affiliations": [
        "Department of Hepato-Gastroenterology and Digestive Oncology, Angers University Hospital, Angers, France",
        "HIFIH Laboratory, SFR ICAT 4208, Angers University, Angers, France"
      ],
      "name": "Jérôme Boursier"
    },
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, Hospital Universitario Puerta de Hierro, Universidad Autonoma de Madrid, Madrid, Spain"
      ],
      "name": "José Luis Calleja"
    },
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore"
      ],
      "name": "George Boon-Bee Goh"
    },
    {
      "affiliations": [
        "Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia"
      ],
      "name": "Wah-Kheong Chan"
    },
    {
      "affiliations": [
        "Digestive Diseases Unit, Virgen del Rocio University Hospital",
        "SeLiver Group, Institute of Biomedicine of Seville (HUVR/CSIC/US)",
        "Ciberehd, ISCIII, Madrid, Department of Medicine, University of Seville, Seville, Spain"
      ],
      "name": "Rocio Gallego-Durán"
    },
    {
      "affiliations": [
        "Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA"
      ],
      "name": "Arun J Sanyal"
    },
    {
      "affiliations": [
        "Echosens, Paris, France"
      ],
      "name": "Victor de Lédinghen"
    },
    {
      "affiliations": [
        "Roger Williams Institute of Liver Studies, Faculty of Life Sciences and Medicine, King’s College London, Foundation for Liver Research & King’s College Hospital, London, UK"
      ],
      "name": "Philip N Newsome"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine",
        "Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China"
      ],
      "name": "Jian-Gao Fan"
    },
    {
      "affiliations": [
        "Université Paris Cité, UMR1149 (CRI), INSERM, Paris, France",
        "Service d'Hépatologie, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris (AP-HP), Clichy, France"
      ],
      "name": "Laurent Castéra"
    },
    {
      "affiliations": [
        "Division of Gastroenterology & Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA"
      ],
      "name": "Michelle Lai"
    },
    {
      "affiliations": [
        "Echosens, Paris, France"
      ],
      "name": "Céline Fournier-Poizat"
    },
    {
      "affiliations": [
        "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"
      ],
      "name": "Grace Lai-Hung Wong"
    },
    {
      "affiliations": [
        "Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine, and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy"
      ],
      "name": "Grazia Pennisi"
    },
    {
      "affiliations": [
        "Department of Medical Sciences, Division of Gastroenterology, A.O.U. Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy"
      ],
      "name": "Angelo Armandi"
    },
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan"
      ],
      "name": "Atsushi Nakajima"
    },
    {
      "affiliations": [
        "Department of Endocrinology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China"
      ],
      "name": "Wen-Yue Liu"
    },
    {
      "affiliations": [
        "Department of Medicine, Karolinska Institutet, Huddinge, Sweden"
      ],
      "name": "Ying Shang"
    },
    {
      "affiliations": [
        "Department of Hepato-Gastroenterology and Digestive Oncology, Angers University Hospital, Angers, France"
      ],
      "name": "Marc de Saint-Loup"
    },
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, Hospital Universitario Puerta de Hierro, Universidad Autonoma de Madrid, Madrid, Spain"
      ],
      "name": "Elba Llop"
    },
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore"
      ],
      "name": "Kevin Kim Jun Teh"
    },
    {
      "affiliations": [
        "Digestive Diseases Unit, Virgen del Rocio University Hospital",
        "SeLiver Group, Institute of Biomedicine of Seville (HUVR/CSIC/US)",
        "Ciberehd, ISCIII, Madrid, Department of Medicine, University of Seville, Seville, Spain"
      ],
      "name": "Carmen Lara-Romero"
    },
    {
      "affiliations": [
        "Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA"
      ],
      "name": "Amon Asgharpour"
    },
    {
      "affiliations": [
        "National Institute for Health Research, Biomedical Research Centre University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, UK"
      ],
      "name": "Sara Mahgoub"
    },
    {
      "affiliations": [
        "Echosens, Paris, France"
      ],
      "name": "Mandy Sau-Wai Chan"
    },
    {
      "affiliations": [
        "Department of Hepato-Gastroenterology and Digestive Oncology, Angers University Hospital, Angers, France",
        "HIFIH Laboratory, SFR ICAT 4208, Angers University, Angers, France"
      ],
      "name": "Adrien Lannes"
    },
    {
      "affiliations": [
        "Digestive Diseases Unit, Virgen del Rocio University Hospital",
        "SeLiver Group, Institute of Biomedicine of Seville (HUVR/CSIC/US)",
        "Ciberehd, ISCIII, Madrid, Department of Medicine, University of Seville, Seville, Spain"
      ],
      "name": "Manuel Romero-Gomez"
    },
    {
      "affiliations": [
        "Ningbo Institute of Liver Diseases, Ningbo No. 2 Hospital, Ningbo, China"
      ],
      "name": "Airong Hu"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, The First Hospital of China Medical University, Shenyang, China"
      ],
      "name": "Yiling Li"
    },
    {
      "affiliations": [
        "Department of Infectious Diseases, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China"
      ],
      "name": "Qing-Lei Zeng"
    },
    {
      "affiliations": [
        "Department of Metabolic Hepatology, Qingdao Sixth People’s Hospital, Qingdao, China"
      ],
      "name": "Wei Gou"
    },
    {
      "affiliations": [
        "Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China"
      ],
      "name": "Hua Bian"
    },
    {
      "affiliations": [
        "Liver Research Center, Beijing Friendship Hospital, Capital Medical University, State Key Lab of Digestive Health, National Clinical Research Center of Digestive Diseases, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, Beijing, China"
      ],
      "name": "Xiao Han"
    },
    {
      "affiliations": [
        "Liver Research Center, Beijing Friendship Hospital, Capital Medical University, State Key Lab of Digestive Health, National Clinical Research Center of Digestive Diseases, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, Beijing, China"
      ],
      "name": "Chenlin Sun"
    },
    {
      "affiliations": [
        "Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea"
      ],
      "name": "Seung Up Kim"
    },
    {
      "affiliations": [
        "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"
      ],
      "name": "Terry Cheuk-Fung Yip"
    },
    {
      "affiliations": [
        "Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University",
        "State Key Laboratory of Digital Medical Engineering, Nanjing, China",
        "Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China"
      ],
      "name": "Gao-Jun Teng"
    },
    {
      "affiliations": [
        "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"
      ],
      "name": "Vincent Wai-Sun Wong"
    },
    {
      "affiliations": [
        "Liver Disease Center of Integrated Traditional Chinese and Western Medicine, Department of Radiology, Zhongda Hospital, Medical School, Southeast University",
        "Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Nanjing, China",
        "Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University",
        "State Key Laboratory of Digital Medical Engineering, Nanjing, China"
      ],
      "name": "Xiaolong Qi"
    },
    {
      "affiliations": [],
      "name": "DiabetesLiver Integrated Management (DLIM) Consortium"
    }
  ],
  "title": "Two-step clinical care pathway to predict MASLD-related advanced fibrosis and long-term outcomes in type 2 diabetes",
  "uid": "78ebf340-2c1a-5462-9800-dee06681d8c2"
}