A study aimed to develop a noninvasive tool to diagnose high-risk metabolic dysfunction-associated steatohepatitis (MASH) using proteomics-derived serum markers and clinical variables. In the discovery phase, a multi-protein predictor was created using SOMAscan proteomics to quantify 1305 serum proteins from 57 US patients. Four key proteins—THBS2, GDF15, SELE, and IGFBP7—were identified and verified through ELISA testing in a larger cohort of 168 US patients. These proteins, combined with clinical factors like age, BMI, ALT levels, diabetes, and hypertension, formed the MASH Dx score, which successfully predicted MASH and high-risk MASH (F2+).

The MASH Dx score showed strong predictive performance, with an AUC of 0.93 in the discovery phase and 0.87 in the validation cohort from the US. External validation in cohorts from Germany (N = 139) and Brazil (N = 177) yielded similar results (AUC: 0.83). This score effectively distinguished MASH from metabolic dysfunction-associated steatotic fatty liver disease without MASH and identified high-risk MASH (F2-4 vs. F0-1). The MASH Dx score provides a reliable, noninvasive method for detecting high-risk MASH, combining novel biomarkers and clinical parameters across diverse patient cohorts from the US, Brazil, and Europe.

Reference: Lai M, Dillon ST, Gu X, et al. Serum protein risk stratification score for diagnostic evaluation of metabolic dysfunction-associated steatohepatitis. Hepatol Commun. 2024 Nov 29;8(12):e0586. doi: 10.1097/HC9.0000000000000586. PMID: 39621304; PMCID: PMC11608748.