Non-invasive blood biomarkers for assessment of liver fibrosis in metabolic dysfunction-associated steatotic liver disease

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) requires accurate liver fibrosis assessment for management. While liver biopsy remains the gold standard, its invasiveness drives demand for non-invasive biomarkers. This review evaluates blood biomarkers for MASLD fibrosis staging. Established scores (fibrosis-4, non-alcoholic fatty liver disease fibrosis score) offer accessible screening but exhibit variable performance influenced by age, obesity, and comorbidities. Patented panels (e.g., enhanced liver fibrosis test, FibroMeter) improve accuracy by integrating extracellular matrix or metabolic markers, though context-specific thresholds are essential. Emerging biomarkers like propeptide of type 3 collagen, Mac-2 binding protein glycosylation isomer, epigenetic markers (proliferator-activated receptor-γ methylation), and angiopoietin-like proteins a family of eight glycoproteins show promise but require large-scale validation. Genetic risk scores and multi-omics approaches face generalizability challenges. Integration strategies, such as combining serum biomarkers with liver stiffness measurement via Agile scores, enhance diagnostic precision and reduce indeterminate classifications. Current tools aid risk stratification, but no single biomarker replicates biopsy-level precision. Future efforts must prioritize MASLD-specific diagnostic frameworks, standardized protocols, and multi-modal integration to enhance clinical utility and address MASLD’s growing burden.

Keywords: Metabolic dysfunction-associated steatotic liver disease; Non-invasive test; Blood biomarkers; Liver fibrosis; Patented panel

Core Tip: Current biomarkers (fibrosis-4, non-alcoholic fatty liver disease fibrosis score) provide accessible first-line screening for metabolic dysfunction-associated steatotic liver disease (MASLD) fibrosis but require age/obesity-adjusted thresholds. Patented panels (enhanced liver fibrosis, FibroMeter) enhance precision through metabolic/extracellular matrix markers yet need MASLD-specific validation. Emerging biomarkers (propeptide of type 3 collagen, Mac-2 binding protein glycosylation isomer, epigenetic regulators like proliferator-activated receptor-γ methylation, angiopoietin-like proteins such as angiopoietin-like protein a family of eight glycoproteins) show monitoring potential but need validation. No single biomarker replaces biopsy. Combining existing tools with novel multi-omics approaches and MASLD-specific diagnostic frameworks is critical for improving clinical outcomes in this epidemic.