title: Apoptosis markers related to pathogenesis of pediatric chronic hepatitis C virus infection: M30 mirrors the severity of steatosis.
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.
authors.affiliation: Laboratory of Molecular Biology, Pathology Division, Ricardo Gutiérrez Children's Hospital, Buenos Aires, Argentina. valvapamela@yahoo.com
authors.forename: Pamela
authors.initials: P
authors.lastname: Valva
authors.forename: Elena
authors.initials: E
authors.lastname: De Matteo
authors.forename: María C
authors.initials: MC
authors.lastname: Galoppo
authors.forename: María I
authors.initials: MI
authors.lastname: Gismondi
authors.forename: María V
authors.initials: MV
authors.lastname: Preciado
mesh_terms: D000293:Adolescent; D017209:Apoptosis; D015415:Biomarkers; D001706:Biopsy; D053148:Caspase 3 / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D005218:Fat Necrosis / Q000175:diagnosis* / Q000473:pathology; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000175:diagnosis / Q000473:pathology*; D006651:Histocytochemistry; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007223:Infant; D053538:Keratin-18 / Q000032:analysis; D008099:Liver / Q000473:pathology* / Q000821:virology*; D008297:Male; D017361:Viral Nonstructural Proteins / Q000032:analysis; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D015415:Biomarkers; D053148:Caspase 3; D053538:Keratin-18; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases