Serum apoptosis markers related to liver damage in chronic hepatitis C: sFas as a marker of advanced fibrosis in children and adults while M30 of severe steatosis only in children

PLoS One. 2013;8(1):e53519. doi: 10.1371/journal.pone.0053519. Epub 2013 Jan 11.

Abstract

Background: Liver biopsy represents the gold standard for evaluating damage and progression in patients with chronic hepatitis C (CHC); however, developing noninvasive tests that can predict liver injury represents a growing medical need. Considering that hepatocyte apoptosis plays a role in CHC pathogenesis; the aim of our study was to evaluate the presence of different apoptosis markers that correlate with liver injury in a cohort of pediatric and adult patients with CHC.

Methods: Liver biopsies and concomitant serum samples from 22 pediatric and 22 adult patients with CHC were analyzed. Histological parameters were evaluated. In serum samples soluble Fas (sFas), caspase activity and caspase-generated neoepitope of the CK-18 proteolytic fragment (M30) were measured.

Results: sFas was associated with fibrosis severity in pediatric (significant fibrosis p = 0.03, advanced fibrosis p = 0.01) and adult patients (advanced fibrosis p = 0.02). M30 levels were elevated in pediatric patients with severe steatosis (p = 0.01) while in adults no relation with any histological variable was observed. Caspase activity levels were higher in pediatric samples with significant fibrosis (p = 0.03) and they were associated with hepatitis severity (p = 0.04) in adult patients. The diagnostic accuracy evaluation demonstrated only a good performance for sFas to evaluate advanced fibrosis both in children (AUROC: 0.812) and adults (AUROC: 0.800) as well as for M30 to determine steatosis severity in children (AUROC: 0.833).

Conclusions: Serum sFas could be considered a possible marker of advanced fibrosis both in pediatric and adult patient with CHC as well as M30 might be a good predictor of steatosis severity in children.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Apoptosis*
  • Biomarkers / blood
  • Biopsy
  • Case-Control Studies
  • Caspases / metabolism
  • Child
  • Child, Preschool
  • Disease Progression*
  • Fatty Liver / blood*
  • Fatty Liver / complications
  • Fatty Liver / diagnosis
  • Fatty Liver / pathology
  • Female
  • Hepatitis C, Chronic / blood*
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / pathology
  • Hepatitis C, Chronic / virology
  • Humans
  • Infant
  • Keratin-18 / blood*
  • Liver / pathology
  • Liver Cirrhosis / blood*
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / diagnosis
  • Liver Cirrhosis / pathology
  • Male
  • Middle Aged
  • Peptide Fragments / blood*
  • Solubility
  • fas Receptor / blood*

Substances

  • Biomarkers
  • FAS protein, human
  • Keratin-18
  • M30 cytokeratin-18 peptide, human
  • Peptide Fragments
  • fas Receptor
  • Caspases

Grants and funding

This study was funded by grants from the International Society for Infectious Diseases, the National Agency for Scientific and Technology Promotion (PICT 2004 N°25344) National Research Council (CONICET) (PIP2010 1392/11). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding received for this study.