Direct serum biomarkers of liver fibrosis in metabolic dysfunction-associated steatotic liver disease: A scoping review.

No systematic reviews assessing the accuracy of direct serum biomarkers of liver fibrosis have been published, and the evidence about their accuracy in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) remains controversial. To systematically summarize and assess existing evidence on the accuracy of direct serum biomarkers of liver fibrosis in MASLD, a scoping review was conducted according to the Joanna Briggs Institute methodology and PRISMA-ScR guidelines. Three databases were systematically searched up to May 2025 for studies reporting the sensitivity, specificity and area under the curve (AUC) for direct serum biomarkers of liver fibrosis (hyaluronic acid [HA], collagen IV [CIV] and CIV7S, procollagen III N-terminal peptide [PIIIP-NP], laminin [LN], cholylglycine [CG]) in biopsy-confirmed MASLD patients. Narrative synthesis of the evidence was conducted. We included 15 studies (12 cohort and 3 cross-sectional studies), involving 1,389 MASLD patients (39.7% with metabolic dysfunction-associated steatohepatitis [MASH]). HA was the most studied biomarker (14 studies), followed by CIV (10), PIIIP-NP (4), CIV7S (5), LN (2) and CG (1). Most studies reported elevated HA, CIV, CIV7S and LN levels in advanced fibrosis (≥F3), with moderate diagnostic accuracy (AUC 0.7-0.97). PIIIP-NP and CG demonstrated inconsistent results. Significant heterogeneity in populations, assays and fibrosis definitions limited cross-study comparability. Direct serum biomarkers seem promising for non-invasive fibrosis assessment in MASLD, but current evidence is limited. Larger, prospective studies integrating HA, CIV and LN into currently available liver disease diagnostic algorithms are required to assess the feasibility of broad clinical implementation for improved value-based healthcare frameworks.