Serum Biomarkers for the Non-Invasive Assessment of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): An Update

Clin Chem. 2026 Jul 10:hvag077. doi: 10.1093/clinchem/hvag077. Online ahead of print.

ABSTRACT

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease, represents the leading cause of chronic liver disease globally. The increasing prevalence of the metabolic syndrome has driven a parallel rise in MASLD-related morbidity and mortality. Accurate assessment of liver fibrosis remains crucial, as liver fibrosis stage is the strongest predictor of adverse clinical outcomes. Liver biopsy, considered the gold standard for assessing liver fibrosis, is invasive and has limitations, prompting the need for reliable noninvasive alternatives.

CONTENT: Serum-based biomarkers have emerged as practical tools for assessing liver fibrosis in MASLD. Conventional indices, including the Fibrosis-4 Index, Nonalcoholic Fatty Liver Disease Fibrosis Score, and aspartate aminotransferase-to-platelet ratio index, are widely used for initial risk stratification due to their simplicity and accessibility. Advanced panels, such as the Enhanced Liver Fibrosis test and the PRO-C3-based ADAPT score, offer improved diagnostic performance but face barriers of cost and limited availability. Novel assays, including the NIS2+™ panel, demonstrate high accuracy for identifying patients with at-risk metabolic dysfunction-associated steatohepatitis. Some biomarkers are currently incorporated in clinical guidelines, though many emerging biomarkers need further validation. There is promise that serum biomarkers can be effectively used to monitor long-term liver disease progression and regression in the future.

SUMMARY: Serum biomarkers provide an effective, noninvasive approach for evaluating liver fibrosis in MASLD. Continued refinement and validation of these assays are essential to standardize cutoff thresholds and improve clinical applicability.

PMID:42429374 | DOI:10.1093/clinchem/hvag077

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