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Parameter
Biomarker CK-18 Full name Cytokeratin-18 Molecular Type Cellular structural proteins (intermediate filament proteins)
Molecular Formula Varies by species (human CK-18: C₄₇₉H₇₄₃N₁₂₅O₁₄₀S₃) Molecular Weight ~53 kDa Core Functional Dimensions Assessment of hepatocyte apoptosis and liver injury
Disease Metabolic Associated Fatty Liver Disease (MASLD) Disease Subtypes /
Organ Liver Test Sample / Technology Platform Serum
Pathobiological Mechanisms Three serum markers (HA, PIIINP, TIMP-1) were calculated by the algorithm. HA reflects the function of hepatic sinusoidal endothelial cells and the degree of fibrosis. PIIINP reflects the rate of collagen synthesis, which is related to the early formation of liver fibrosis. TIMP-1 inhibits matrix metalloproteinase activity, inhibits collagen degradation, and promotes the progression of fibrosis. The ELF score can quantify the degree of liver fibrosis, and the higher the value, the more severe the fibrosis CK-18 is the main cytoskeletal protein in the cytoplasm of hepatocytes, which maintains the structural integrity of hepatocytes. When hepatocyte apoptosis occurs in MASLD patients, caspases cleave CK-18 to produce M30 fragment. Intact CK-18 (M65 fragment) was released in necrotic hepatocytes. In NASH, hepatocyte apoptosis is the core pathological feature. The level of M30 fragment is positively correlated with the degree of hepatic steatosis, lobular inflammation and fibrosis, and can specifically reflect the activity of hepatocyte apoptosis. M65 fragment can reflect the total hepatocyte injury of apoptosis and necrosis comprehensively
Clinical Availability Status In the clinical research stage, serum has been widely used in disease stratification, prognosis evaluation and drug clinical trials of MASLD (especially NASH). For example, evaluating the inhibitory effect of drugs such as toagliflozin and pioglitazone on hepatocyte apoptosis is also used to distinguish simple fatty liver from NASH
Notes and Dynamics CK-18 (M30 fragment) is a specific biomarker reflecting hepatocyte apoptosis, which makes up for the deficiency of ALT/AST and other traditional indicators that are difficult to distinguish the types of hepatocyte injury (apoptosis/necrosis), and can indicate the occurrence and progression risk of NASH at an early stage. The detection is convenient and minimally invasive, but the current detection methods have not been fully standardized, and there are differences in the reference ranges of different laboratories. In the severe stage of liver fibrosis, the level may be false negative due to the reduction of the number of hepatocytes, which needs to be comprehensively interpreted in combination with ELF score, LSM and other indicators

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This study was supported by the Scientific Research Innovation Capability Support Project for Young Faculty (SRICSPYF-ZY2025112), the Fundamental and Interdisciplinary Disciplines Breakthrough Plan of the Ministry of Education of China (JYB2025XDXM612)

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