Letter to the Editor: Evaluating cytokeratin 18 fragment as a non-invasive marker of fibrosis and lipid alterations in steatotic liver disease

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) arises from the interplay between disordered lipid metabolism, hepatocellular injury, and systemic inflammation. Ichikawa et al published a study in the recent issue of the World Journal of Hepatology, explored the clinical value of circulating cytokeratin 18 fragment (CK18F), a marker of hepatocyte apoptosis, among individuals with steatotic liver disease. The study found that CK18F concentrations were closely linked to biochemical indicators of liver injury and lipid abnormalities-most notably elevated triglycerides and reduced high-density lipoprotein; cholesterol-while showing little association with conventional fibrosis scores such as fibrosis-4 index or liver stiffness measurements. Conversely, CK18F demonstrated strong alignment with integrative non-invasive indices, including the FibroScan-aspartate aminotransferase and Steatosis-Associated Fibrosis Estimator scores. These results indicate that CK18F primarily reflects active hepatic injury and metabolic stress rather than established fibrosis. Incorporating CK18F into existing non-invasive evaluation frameworks could improve the early detection of metabolically active MASLD, refine patient risk stratification, and support targeted lifestyle and therapeutic interventions aimed at preventing disease progression.

Keywords: Cytokeratin 18 fragment; Steatotic liver disease; Metabolic dysfunction-associated steatotic liver disease; Hepatocyte apoptosis; FibroScan-aspartate aminotransferase score; Steatosis-Associated Fibrosis Estimator score; Non-invasive biomarkers; Lipid metabolism; Liver injury; Metabolic dysfunction

Core Tip: Ichikawa et al examined the diagnostic utility of serum cytokeratin 18 fragment (CK18F) in patients with steatotic liver disease (SLD). Their findings demonstrated that CK18F-a marker of hepatocyte apoptosis-shows a strong relationship with liver injury markers and lipid disturbances, particularly elevated triglycerides, but not with conventional fibrosis indices. Notably, CK18F correlated closely with non-invasive composite scores such as FibroScan-aspartate aminotransferase and Steatosis-Associated Fibrosis Estimator, emphasizing its ability to reflect active hepatic inflammation and metabolic stress rather than fibrotic burden. These results suggest that incorporating CK18F into existing non-invasive assessment tools could enhance early detection and clinical stratification of individuals at metabolic and hepatic risk within the spectrum of metabolic dysfunction-associated SLD.