Elevated apoptosis-associated cytokeratin 18 fragments (CK18Asp386) in serum of patients with chronic liver diseases indicate hepatic and biliary inflammation

Objectives: During apoptosis, intermediate filament protein cytokeratin 18 (CK18) is cleaved by caspases at Asp396 which can be specifically detected by the monoclonal antibody M30 (M30-antigen). Design and methods: M30-antigen serum levels were analyzed in 76 chronic liver diseases (CLD) patients and 62 healthy controls. Results: M30-antigen levels were significantly elevated in CLD patients (median 296.3 U/L) compared with healthy controls (median 153.5 U/L, P < 0.001) and increased with disease severity (Child-Pugh or MELD score). M30-antigen correlated with aminotransferase activities and parameters indicating cholestasis such as bile acids. Highest serum M30-antigen was associated with histologically confirmed severe intrahepatic cholestasis (median 599.1 U/L) or biliary duct inflammation (median 648.0 U/L). Furthermore, in contrast to patients with liver cirrhosis, presence of hepatocellular carcinoma was associated with elevated M30-antigen in patients without cirrhosis. Conclusion: Serum M30-antigen levels are elevated in CLD and correlate with hepatic inflammation as well as cholangitis and cholestasis.