Apoptosis markers related to pathogenesis of pediatric chronic hepatitis C virus infection: M30 mirrors the severity of steatosis

J Med Virol. 2010 May;82(6):949-57. doi: 10.1002/jmv.21699.

Abstract

Apoptosis involvement in liver damage related to hepatitis C virus (HCV) chronic infection has been suggested. Although liver biopsy represents the gold standard for evaluating disease severity, non-invasive tests are a growing medical need. The aim of this study was to detect apoptosis markers in liver and serum from pediatric HCV-infected patients and to assess its utility to predict liver damage progression. Twenty-three patients were included. Liver biopsies were used for histological analysis as well as for immunodetection of a viral protein (NS3) and apoptosis markers (activated caspase-3 [casp-3a], caspase-generated CK-18 fragment [M30] and TUNEL). M30 was quantified in paired serum and biopsy samples. NS3 correlated both with casp-3a (r = 0.83, P < 0.0001) and TUNEL (r = 0.61, P < 0.0017). Casp-3a and TUNEL also displayed a correlation (r = 0.56, P = 0.005). Both NS3 and casp-3a were associated with fibrosis stage (P = 0.03). Serum M30 [median: 122.15 UL-1 (86.68-794.58)] was higher in patients than in controls [median: 81.44 UL-1 (41.17-129.30)], (P < 0.0001). M30 showed a correlation with steatosis, and indeed it was linked to severe grade (P = 0.004). In children, HCV would be involved in liver damage through apoptosis induction. The apoptosis markers detected reflect liver injury. Serum M30 might be useful as a marker to detect the extent of liver steatosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Apoptosis*
  • Biomarkers
  • Biopsy
  • Caspase 3 / analysis
  • Child
  • Child, Preschool
  • Fat Necrosis / diagnosis*
  • Fat Necrosis / pathology
  • Female
  • Hepatitis C, Chronic / complications*
  • Hepatitis C, Chronic / diagnosis
  • Hepatitis C, Chronic / pathology*
  • Histocytochemistry
  • Humans
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Infant
  • Keratin-18 / analysis
  • Liver / pathology*
  • Liver / virology*
  • Male
  • Viral Nonstructural Proteins / analysis

Substances

  • Biomarkers
  • Keratin-18
  • NS3 protein, hepatitis C virus
  • Viral Nonstructural Proteins
  • Caspase 3