A blood-based biomarker panel for non-invasive diagnosis of metabolic dysfunction-associated steatohepatitis

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. [Display omitted] •We establish N3-MASH panel that discriminates MASLD from healthy controls, AUROC 0.950•N3-MASH distinguishes MASH in MASLD patients with AUROC 0.823 in the discovery cohort•N3-MASH performance is validated in 3 independent cohorts across Asia and America•N3-MASH identifies patients with MASH improvement with an AUROC of 0.857 Zhang et al. developed a robust blood-based biomarker panel for the non-invasive diagnosis of metabolic dysfunction-associated steatohepatitis (MASH) among patients with metabolic dysfunction-associated steatotic liver disease (MASLD). The biomarker panel demonstrates high diagnostic accuracy with three independent cohort validations in Asia and America, thus highlighting its potential clinical utility in non-invasive diagnosis of MASH in MASLD patients.