Total Keratin-18 (M65) as a Potential, Early, Non-Invasive Biomarker of Hepatocyte Injury in Alcohol Intoxicated Adolescents-A Preliminary Study

Biomolecules. 2021 Jun 18;11(6):911. doi: 10.3390/biom11060911.

Abstract

Background: Underage drinking is associated with health risk behaviors. Serum keratin-18 (CK18) levels are increased in liver diseases and may be biomarkers of outcome. The purpose of this study was to determine if the total CK18 (M65) or caspase-cleaved CK18 (M30) levels were different in adolescents admitted to hospital because of alcohol intoxication and controls with excluded liver diseases.

Methods: A prospective study included 57 adolescents after alcohol use and 23 control subjects. The concentrations of M30 and M65 in the serum samples were evaluated using an enzyme-linked immunosorbent assay.

Results: The median age was 15 (14-17) years and 49% were male. There were significant differences in M65 levels between the study and control groups (p = 0.03). The concentrations of M30 and M65 were insignificant in adolescents divided into subgroups according to blood alcohol concentrations (BAC). Significant positive correlations were found between BAC and M65 levels (p = 0.038; r = 0.3). In receiver operating characteristic (ROC) analysis M65 (cut-off = 125.966 IU/l, Se = 70.2%, Sp = 43.5%) allowed to differentiate between patients with and without alcohol intoxication (AUC = 0.66, p = 0.03).

Conclusion: M65 appears to be a promising non-invasive biomarker of hepatocyte injury during alcohol intoxication in adolescents. Moreover, a higher concentration of M65 may indicate early organ injury before the increase in the activity of liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST).

Keywords: Keratin-18; M65; adolescents; apoptosis; ethanol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Alanine Transaminase / blood
  • Alcoholic Intoxication / blood
  • Alcoholic Intoxication / physiopathology
  • Apoptosis
  • Aspartate Aminotransferases / blood
  • Biomarkers / blood
  • Chemical and Drug Induced Liver Injury / blood
  • Chemical and Drug Induced Liver Injury / diagnosis*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Hepatocytes / metabolism
  • Hepatocytes / pathology*
  • Humans
  • Keratin-18 / analysis*
  • Keratin-18 / blood
  • Male
  • Peptide Fragments / blood
  • Poland
  • Preliminary Data
  • Prospective Studies
  • ROC Curve
  • Underage Drinking

Substances

  • Biomarkers
  • KRT18 protein, human
  • Keratin-18
  • Peptide Fragments
  • Aspartate Aminotransferases
  • Alanine Transaminase