Liver function tests and metabolic-associated fatty liver disease: Changes in upper normal limits, does it really...

Area of Science:

• Hepatology
• Biochemistry
• Clinical Diagnostics

Background:

• Metabolic-associated fatty liver disease (MAFLD) is the most prevalent cause of abnormal liver function tests (LFTs).
• Current upper normal limits (UNLs) for LFTs may not accurately reflect disease presence, potentially masking undiagnosed MAFLD or viral hepatitis.
• The diagnostic utility of LFTs in MAFLD requires re-evaluation.

Purpose of the Study:

• To evaluate the implications of altering the upper normal limit (UNL) for alanine aminotransferase (ALT) in patients with MAFLD.
• To assess the impact of revised LFT UNLs on the detection of significant liver disease, including advanced fibrosis and metabolic-associated steato-hepatitis (MASH).

Main Methods:

• Retrospective analysis of 436 patients diagnosed with MAFLD between 2010 and 2017.
• Comparison of diagnostic outcomes using conventional LFT UNLs versus a proposed lower UNL for ALT.
• Liver biopsy data was available for 288 patients to confirm fibrosis and MASH staging.

Main Results:

• A lower ALT UNL decreased the proportion of patients with significant disease (advanced fibrosis or MASH) who had normal ALT levels.
• Conversely, a lower ALT UNL increased the proportion of patients with elevated ALT but without advanced fibrosis or MASH.
• Liver function tests demonstrated poor performance in distinguishing MASH from simple steatosis, with low AUC values for both ALT and AST.

Conclusions:

• Liver function tests may inaccurately overestimate or underestimate the severity of MASH-related liver disease.
• Reducing LFT UNLs may not be clinically beneficial and could increase healthcare costs.
• Risk stratification for MAFLD should integrate multiple risk factors rather than relying solely on LFTs.