Development and validation of an image biomarker to identify metabolic dysfunction associated steatohepatitis: MR–MASH score

Abstract Background and Aims Diagnosis of metabolic dysfunction‐associated steatohepatitis (MASH) requires histology. In this study, a magnetic resonance imaging (MRI) score was developed and validated to identify MASH in patients with metabolic dysfunction‐associated steatotic liver disease (MASLD). Secondarily, a screening strategy for MASH diagnosis was investigated. Methods This prospective multicentre study included 317 patients with biopsy‐proven MASLD and contemporaneous MRI. The discovery cohort (Spain, Portugal) included 194 patients. NAFLD activity score (NAS) and fibrosis were assessed with the NASH‐CRN histologic system. MASH was defined by the presence of steatosis, lobular inflammation, and ballooning, with NAS ≥4 with or without fibrosis. An MRI‐based composite biomarker of Proton Density Fat Fraction and waist circumference (MR–MASH score) was developed. Findings were afterwards validated in an independent cohort (United States, Spain) with different MRI protocols. Results In the derivation cohort, 51% ( n = 99) had MASH. The MR–MASH score identified MASH with an AUC = .88 (95% CI .83–.93) and strongly correlated with NAS ( r = .69). The MRI score lower cut‐off corresponded to 88% sensitivity with 86% NPV, while the upper cut‐off corresponded to 92% specificity with 87% PPV. MR–MASH was validated with an AUC = .86 (95% CI .77–.92), 91% sensitivity (lower cut‐off) and 87% specificity (upper cut‐off). A two‐step screening strategy with sequential MR–MASH examination performed in patients with indeterminate‐high FIB‐4 or transient elastography showed an 83–84% PPV to identify MASH. The AUC of MR–MASH was significantly higher than that of the FAST score ( p < .001). Conclusions The MR–MASH score has clinical utility in the identification and management of patients with MASH at risk of progression.