Prognostic Value of Serum Caspase-Cleaved Cytokeratin-18 Levels before Liver Transplantation for One-Year Survival of Patients with Hepatocellular Carcinoma

Int J Mol Sci. 2016 Sep 9;17(9):1524. doi: 10.3390/ijms17091524.

Abstract

Cytokeratin (CK)-18 is the major intermediate filament protein in the liver and during hepatocyte apoptosis is cleaved by the action of caspases; the resulting fragments are released into the blood as caspase-cleaved cytokeratin (CCCK)-18. Higher circulating levels of CCCK-18 have been found in patients with hepatocellular carcinoma (HCC) than in healthy controls and than in cirrhotic patients. However, it is unknown whether serum CCCK-18 levels before liver transplantation (LT) in patients with HCC could be used as a prognostic biomarker of one-year survival, and this was the objective of our study with 135 patients. At one year after LT, non-survivors showed higher serum CCCK-18 levels than survivors (p = 0.001). On binary logistic regression analysis, serum CCCK-18 levels >384 U/L were associated with death at one year (odds ratio = 19.801; 95% confidence interval = 5.301-73.972; p < 0.001) after controlling for deceased donor age. The area under the receiver operating characteristic (ROC) curve of serum CCCK-18 levels to predict death at one year was 77% (95% CI = 69%-84%; p < 0.001). The new finding of our study was that serum levels of CCCK-18 before LT in patients with HCC could be used as prognostic biomarker of survival.

Keywords: cytokeratin; hepatocellular carcinoma; liver transplantation; mortality; outcome.

MeSH terms

  • Biomarkers / blood
  • Carcinoma, Hepatocellular / blood*
  • Carcinoma, Hepatocellular / therapy
  • Caspases / metabolism
  • Female
  • Humans
  • Keratin-18 / blood
  • Keratin-18 / chemistry*
  • Liver Neoplasms / blood*
  • Liver Neoplasms / therapy
  • Liver Transplantation
  • Male
  • Middle Aged
  • Peptide Fragments / blood*
  • Prognosis
  • ROC Curve
  • Survival Analysis

Substances

  • Biomarkers
  • KRT18 protein, human
  • Keratin-18
  • Peptide Fragments
  • Caspases