Two-step clinical care pathway to predict MASLD-related advanced fibrosis and long-term outcomes in type 2 diabetes
Chen, Yuping Dong, Bingtian Jin, Xinrui Liu, Chuan Zheng, Ming-Hua Liang, Xiao Sun, Yameng Lee, Hye Won Lin, Huapeng Tsochatzis, Emmanuel
Chen, Yuping
Dong, Bingtian
Jin, Xinrui
Liu, Chuan
Zheng, Ming-Hua
Liang, Xiao
Sun, Yameng
Lee, Hye Won
Lin, Huapeng
Tsochatzis, Emmanuel
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.
MIDER Authors
Affiliations
Zhongda Hospital; Southeast University; State Key Laboratory of Digital Medical Engineering; The First Affiliated Hospital of Anhui Medical University; The Chinese University of Hong Kong; First Affiliated Hospital of Wenzhou Medical University; Sir Run-Run Shaw Hospital; Zhejiang University; Beijing Friendship Hospital; Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis; Yonsei University; Shanghai Ninth People's Hospital; Shanghai Jiao Tong University; University College London; Royal Free London NHS Foundation Trust; University of Palermo; University of Turin; Yokohama City University; Karolinska Institutet; Karolinska University Hospital; Angers University Hospital; Angers University; Hospital Universitario Puerta de Hierro; Universidad Autonoma de Madrid; Singapore General Hospital; Universiti Malaya; Virgen del Rocio University Hospital; University of Seville; Virginia Commonwealth University; Echosens; King's College London; Foundation for Liver Research; King's College Hospital NHS Foundation Trust; Xinhua Hospital; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition; Université Paris Cité; Assistance Publique-Hôpitaux de Paris; Beth Israel Deaconess Medical Center; Harvard Medical School; University Hospitals Birmingham NHS Foundation Trust; University of Birmingham; Ningbo No. 2 Hospital; The First Hospital of China Medical University; First Affiliated Hospital of Zhengzhou University; Qingdao Sixth People's Hospital; Zhongshan Hospital; Fudan University
Date
2026-02-09
Type
Article
Collections
Citation
Chen Y, Dong B, Jin X, Liu C, Zheng MH, Liang X, Sun Y, Lee HW, Lin H, Tsochatzis E, Petta S, Bugianesi E, Yoneda M, Hagström H, Boursier J, Calleja JL, Goh GB, Chan WK, Gallego-Durán R, Sanyal AJ, de Lédinghen V, Newsome PN, Fan JG, Castéra L, Lai M, Fournier-Poizat C, Wong GL, Pennisi G, Armandi A, Nakajima A, Liu WY, Shang Y, Saint-Loup M, Llop E, Teh KKJ, Lara-Romero C, Asgharpour A, Mahgoub S, Chan MS, Lannes A, Romero-Gomez M, Hu A, Li Y, Zeng QL, Gou W, Bian H, Han X, Sun C, Kim SU, Yip TC, Teng GJ, Wong VW, Qi X; DiabetesLiver Integrated Management (DLIM) Consortium. Two-step clinical care pathway to predict MASLD-related advanced fibrosis and long-term outcomes in type 2 diabetes. Gut. 2026 Feb 9;75(3):576-587. doi: 10.1136/gutjnl-2025-337506.