Background and aim: Steatotic liver disease (SLD) is now the most common chronic liver disease, with the potential to progress to cirrhosis and hepatocellular carcinoma (HCC). Although alanine aminotransferase (ALT) is commonly used for screening patients with SLD, disease progression can occur despite normal ALT levels. Therefore, we investigated the prevalence and clinical characteristics of SLD in patients with normal ALT levels and assessed the diagnostic performance of the fatty liver index (FLI), fibrosis-4 index (FIB-4), and AST-to-platelet ratio index (APRI) in diagnosing steatosis and fibrosis.
Methods: A total of 2394 adults undergoing health checkups were assessed for steatosis and fibrosis using attenuation imaging (ATT) and point shear wave elastography (pSWE). SLD and significant fibrosis were defined as ≥ S1 steatosis and ≥ F2 fibrosis, respectively.
Results: Of the 2394 adults, 35.5% had SLD. Among them, 70.5% had normal ALT levels (< 30 IU/L), of which 6.4% had significant fibrosis. The FLI demonstrated good diagnostic accuracy for steatosis regardless of ALT levels. However, the FIB-4 index and APRI showed poor accuracy for detecting significant fibrosis in patients with normal ALT (area under the receiver operating characteristics curve: 0.527 and 0.557, respectively). Multivariate analysis showed that older age, male sex, and diabetes were independently associated with significant fibrosis in these patients.
Conclusions: A considerable proportion of patients with SLD and with normal ALT levels have unrecognized significant fibrosis. These findings highlight the diagnostic limitations of ALT and conventional indices and the urgent need for alternative strategies incorporating noninvasive imaging and direct fibrosis biomarkers.
Keywords: alanine aminotransferase; attenuation imaging; point shear wave elastography; significant fibrosis; steatotic liver disease.
© 2025 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.