Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD): Biochemical Pathways, Clinical Spectrum, and Biomarker Profiling: A Comprehensive Review

Abstract

Metabolic Dysfunction–Associated Steatotic Liver Disease (MASLD) is the most common chronic liver disease in the world. The nomenclature was changed lately to stress its strong metabolic basis.   It has a high risk of morbidity in the liver and outside of it, and it is significantly linked to being overweight, having type 2 diabetic mellitus (T2DM), and having high cholesterol. This review attempts to provide a thorough rundown of MASLD, emphasizing biochemical pathways, clinical spectrum, and current and emerging biomarkers relevant for diagnosis and prognosis. There was a review of narrative literature undertaken using peer-reviewed articles indexed in Scopus and PubMed (2014–2024). Priority was given to Q1 journals and international consensus guidelines. MASLD pathogenesis is driven by insulin resistance, lipotoxicity, oxidative stress, and immunometabolic dysregulation. Genetic and epigenetic modifiers, alongside gut microbiota alterations, further modulate disease progression. Biochemical pathways involve impaired lipid metabolism, mitochondrial dysfunction, and fibrogenic signaling. Biomarker profiling, including cytokeratin-18, fibrosis panels (FIB-4, ELF), imaging modalities (FibroScan, MRI-PDFF), and emerging molecular biomarkers (microRNAs, metabolomics), has improved noninvasive diagnosis. The mainstay of treatment is still lifestyle change, although there is hope for pharmacological treatments such pioglitazone, GLP-1 receptor agonists, and experimental drugs including FXR agonists and FGF21 analogs. MASLD represents a multisystem disease with substantial health and economic burden. Advances in biomarker discovery and therapeutic strategies highlight the importance of integrating biochemical and molecular insights into clinical practice. Precision medicine strategies to enhance risk assessment and patient outcomes should be the main focus of future studies.