Optimal ALT threshold for the automated diagnosis of MASLD: A population-based study using iLFT

Area of Science:

• Hepatology
• Primary Care Medicine
• Diagnostic Biomarkers

Background:

• Metabolic dysfunction-associated steatotic liver disease (MASLD) diagnosis, particularly advanced fibrosis, is critical for patient outcomes.
• Conventional alanine aminotransferase (ALT) thresholds (<55 U/L) may miss MASLD patients with significant liver disease.
• Intelligent liver function testing (iLFT) offers a pathway for improved diagnostic strategies.

Purpose of the Study:

• To evaluate the clinical utility of a lower ALT cut-off (>30 U/L) for identifying MASLD patients with and without advanced fibrosis in primary care.
• To assess the proportion of MASLD patients with advanced fibrosis missed by the standard ALT range.
• To investigate the diagnostic yield of iLFT in a primary care setting for MASLD.

Main Methods:

• A cohort of 16,373 patients undergoing iLFT between March 2016 and April 2022 were analyzed.
• Patients with MASLD were stratified based on ALT levels (31-41 U/L, 42-54 U/L, and ≥55 U/L) and fibrosis status.
• Proportions of patients with and without advanced fibrosis were compared across different ALT thresholds.

Main Results:

• Out of 16,373 patients, 762 (5%) had MASLD with abnormal fibrosis scores and 908 (6%) had MASLD with normal fibrosis scores.
• Among patients assessed in liver clinics, 145 (86%) had advanced fibrosis or cirrhosis.
• A significant proportion (33%) of MASLD patients with advanced fibrosis or cirrhosis had ALT levels between 31-54 U/L, falling within the conventional normal range.

Conclusions:

• Lowering the ALT cut-off to >30 U/L significantly improves the detection of MASLD patients with advanced fibrosis in primary care.
• The conventional ALT range (<55 U/L) fails to identify a substantial number of MASLD patients with advanced liver disease.
• Implementing a lower ALT threshold within iLFT pathways can enhance early diagnosis and management of MASLD.