Yuping Chen, Bingtian Dong, Xinrui Jin, Chuan Liu, Ming-Hua Zheng, Xiao Liang, Yameng Sun, Hye Won Lee, Huapeng Lin, Emmanuel Tsochatzis, Salvatore Petta, Elisabetta Bugianesi, Masato Yoneda, Hannes Hagström, Jérôme Boursier, Calleja Jl, George Boon-Bee Goh, W. F. Chan, Rocio Gallego-Durán, Arun J Sanyal, Victor de Lédinghen, Philip N Newsome, Jian-Gao Fan, Laurent Castéra, Michelle Lai, Céline Fournier-Poizat, Grace Lai-Hung Wong, Grazia Pennisi, Angelo Armandi, A. Nakajima, Wen-Yue Liu, Ying Shang, Marc de Saint-Loup, Elba Llop, Kevin Teh, Carmen Lara-Romero, Amon Asgharpour, Sara Mahgoub, Mandy Sau-Wai Chan, Adrien Lannes, Manuel Romero-Gomez, Airong Hu, Yiling Li, Qinglei Zeng, Wei Gou, Hua Bian, Xiao Han, Chenlin Sun, Seung Up Kim, Terry Cheuk-Fung Yip, Gao‐Jun Teng, Vincent Wai-Sun Wong, Xiaolong Qi
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.