Caspase-cleaved cytokeratin 18 and 20S proteasome in liver degeneration

Apoptosis of epithelial hepatocytes plays a pivotal role in acute as well as in chronic liver diseases. The cleavage of cytokeratin-18 (CK-18) by caspases is an early event in the apoptotic process. We therefore sought to investigate serum levels of CK-18 and 20S proteasome in patients with liver cirrhosis, primary graft dysfunction (PDF), and acute liver failure (ALF), and in healthy volunteers. Enzyme-linked immunosorbent assay (ELISA) was utilized to measure the concentration of M30, a fragment of CK-18 cleaved at Asp396 (M30 neoantigen), and the concentration of 20S proteasome. Serum levels of the CK-18 neoepitope M30 were significantly increased in ALF, primary graft dysfunction, and liver cirrhosis vs. healthy controls (1,993.6 +/- 124.7 U/L, 2,238.1 +/- 235.9 U/L, and 673.6 +/- 86.5 U/L vs. 66.8 +/- 29.1 U/L, respectively, P < 0.001). Similar results were detected with the evaluation of 20S proteasome (124,014.5 +/- 13,235.6ng/mL, 76,993.2 +/- 15,720.1 ng/mL, and 2,395.9 +/- 1,098.2 ng/mL vs. 1,074.5 +/- 259.4 ng/mL, respectively; P < 0.001). Detection of CK-18 neoepitope M30 and 20S proteasome may represent a novel marker of tracing apoptotic epithelium, respectively mirroring degenerative liver processes in affected patient population.