ABSTRACT Background & Aims Identifying at‐risk metabolic dysfunction‐associated steatohepatitis (MASH with ≥ stage 2 fibrosis) is critical. While the steatosis‐associated fibrosis estimator (SAFE) score effectively stages significant fibrosis (≥ stage 2 fibrosis) and the MR‐MASH score detects MASH, their combined performance remains unclear. Methods This two‐part study evaluated serial combinations of non‐invasive tests for at‐risk MASH in clinical and population‐based settings. In part 1, we analysed 286 patients with metabolic dysfunction‐associated steatotic liver disease (MASLD) from an Asian center with biopsy‐proven diagnoses. Four two‐step strategies were compared. In part 2, 495 MASLD patients from the UK Biobank with corrected T1 values were used to validate selected strategies. Results In part 1, the combination of SAFE followed by the MR‐MASH for at‐risk MASH (strategy A) showed higher accuracy than SAFE followed by FibroScan‐AST (FAST) score and FIB‐4 followed by FAST (87.8% vs. 69.1% and 71.2%, both p < 0.01) and similar misclassification rates (10.1% vs. 11.5% and 11.5%, both p = 0.83). Compared with Fibrosis‐4 followed by magnetic resonance‐based model (strategy B), strategy A had a higher accuracy (88.5% vs. 83.9%, p < 0.01) and a lower misclassification rate (9.1% vs. 12.9%, p < 0.01). In part 2, strategy A maintained a high negative predictive value (99.7%) and showed lower misclassification than strategy B (3.6% vs. 5.7%, p = 0.03), with similar accuracy (82.6% vs. 82.0%, p = 0.74) and indeterminate rates (13.7% vs. 12.3%, p = 0.19). Conclusions Serial combination of SAFE and MR‐MASH performs well in predicting at‐risk MASH.
Li et al. (Thu,) studied this question.