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. (c) 2007 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.