Identifying MASLD Patients with MASH or Significant Fibrosis: The Role of Lower ALT Thresholds

Background: Serum ALT is widely used to assess liver inflammation and fibrosis, yet metabolic steatohepatitis (MASH) and significant fibrosis can still occur in metabolic dysfunction-associated steatotic liver disease (MASLD) patients with normal ALT. However, liver histology in patients with ALT below the cutoffs remains poorly characterized. This study aimed to compare the diagnostic performance of conventional and lower ALT thresholds for assessing MASH and significant fibrosis, using liver biopsy as the reference standard. Materials: This retrospective cross-sectional, two-center study included 404 patients with MASLD, without concurrent viral hepatitis, who underwent liver biopsy at two hospitals in Tianjin between October 2012 and October 2024. The assessment of inflammation and fibrosis was based on liver biopsy histology. Patients were stratified using both conventional and lower ALT thresholds (30 U/L for men, 19 U/L for women). Results: Among the 404 patients, 70.3% had MASH and 67.1% had significant fibrosis. Of those with conventionally normal ALT levels (n = 130), the prevalence of MASH and significant fibrosis was 49.23% and 50.00%, respectively. Using a lower ALT threshold, patients with ALT between the conventional and lower thresholds had significantly higher rates of significant fibrosis compared to those with ALT below the lower threshold (56.18% vs. 36.59%, p = 0.002). The incidence of MASH also showed a decreasing trend in the lower ALT group (53.93% vs. 39.02%, p = 0.082). Multivariate analysis showed that the application of a lower ALT ULN was independently associated with MASH (OR = 5.188, 95% CI: 1.494–18.018, p < 0.001). Conclusions: The study evaluated the association between liver histology and ALT under alternative externally proposed ALT thresholds. The lower ALT threshold was independently associated with MASH, but its diagnostic performance was limited; further prospective evaluation is warranted.