Zhang Xiang, Zheng Ming-Hua, Liu Dehua, Lin Yufeng, Song Sherlot Juan, Chu Eagle Siu-Hong, Liu Dabin, Singh Seema, Berman Michael, Lau Harry Cheuk-Hay, Gou Hongyan, Wong Grace Lai-Hung, Zhang Ni, Yuan Hai-Yang, Loomba Rohit, Wong Vincent Wai-Sun, Yu Jun
Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shenzhen Research Institute, Hong Kong SAR, China.
MAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Cell Metab. 2025 Jan 7;37(1):59-68.e3. doi: 10.1016/j.cmet.2024.10.008. Epub 2024 Nov 4.
The current diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD) and its severe form, metabolic dysfunction-associated steatohepatitis (MASH), is suboptimal. Here, we recruited 700 individuals, including 184 from Hong Kong as a discovery cohort and 516 from San Diego, Wenzhou, and Hong Kong as three validation cohorts. A panel of 3 parameters (C-X-C motif chemokine ligand 10 [CXCL10], cytokeratin 18 fragments M30 [CK-18], and adjusted body mass index [BMI]) was formulated (termed N3-MASH), which discriminated patients with MASLD from healthy controls with an area under the receiver operating characteristic (AUROC) of 0.954. Among patients with MASLD, N3-MASH could identify patients with MASH with an AUROC of 0.823, achieving 90.0% specificity, 62.9% sensitivity, and 88.6% positive predictive value. The diagnostic performance of N3-MASH was confirmed in three validation cohorts with AUROC of 0.802, 0.805, and 0.823, respectively. Additionally, N3-MASH identifies patients with MASH improvement with an AUROC of 0.857. In summary, we developed a robust blood-based panel for the non-invasive diagnosis of MASH, which might help clinicians reduce unnecessary liver biopsies.
目前对代谢功能障碍相关脂肪性肝病（MASLD）及其严重形式代谢功能障碍相关脂肪性肝炎（MASH）的诊断并不理想。在此，我们招募了700名个体，其中包括来自香港的184名作为发现队列，以及来自圣地亚哥、温州和香港的516名作为三个验证队列。制定了一个由3个参数组成的指标（C-X-C基序趋化因子配体10 [CXCL10]、细胞角蛋白18片段M30 [CK-18]和校正体重指数[BMI]）（称为N3-MASH），其在受试者操作特征曲线下面积（AUROC）为0.954，可将MASLD患者与健康对照区分开来。在MASLD患者中，N3-MASH能够识别MASH患者，AUROC为0.823，特异性达到90.0%，敏感性为62.9%，阳性预测值为88.6%。N3-MASH的诊断性能在三个验证队列中得到证实，AUROC分别为0.802、0.805和0.823。此外，N3-MASH能够识别MASH病情改善的患者，AUROC为0.857。总之，我们开发了一种强大的基于血液的指标用于MASH的非侵入性诊断，这可能有助于临床医生减少不必要的肝脏活检。
