Tips for Hepatologist Referral of Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease with Alanine Aminotransferase Levels ≤ 30 U/L.

The possibility of progressive liver fibrosis remains even when alanine aminotransferase (ALT) levels are <30 IU/L. Therefore, we aimed to investigate factors that can predict fibrosis progression in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) with ALT levels ≤ 30 U/L. This multicenter retrospective cohort study was conducted using data collected between December 1994 and December 2021. Among the 1381 patients with MASLD (CLIONE study) who underwent liver biopsy, we performed decision-tree analysis on factors for stage ≥ 3 in 115 with ALT levels ≤ 30 U/L. Of the 818 patients with MASLD (Kawasaki cohort) who underwent liver biopsy, we included 174 with ALT levels ≤ 30 U/L for validation. In the decision-tree analysis of patients with stage ≥ 3 with ALT levels ≤ 30 U/L, 57% of patients with a fibrosis-4 (FIB-4) index ≥ 2.67 and 70% with both FIB-4 index ≥ 2.67 and type-2 diabetes mellitus (DM) were detected. However, no cases of stage ≥ 3 were observed among patients without type-2 DM with ALT ≤ 30 U/L and a FIB-4 index < 2.67. After verifying the decision-tree analysis, the model construction and validation datasets showed a close correlation. Among patients with MASLD with ALT levels ≤ 30 U/L, those with an FIB-4 index ≥ 2.67, particularly with comorbid type-2 DM, should consider consultation with a hepatologist.