title: Apoptosis markers in liver biopsy of nonalcoholic steatohepatitis in pediatric patients.
abstract: The natural history of pediatric nonalcoholic steatohepatitis is still unknown; however, there are differences between adult and pediatric presentation. Apoptosis may play an important role in pathophysiologic pathways involved in liver damage and progression. Our aim was to detect early apoptosis markers, activated caspase-3 and cleaved cytokeratin-18, in hepatocytes and to correlate their presence with clinical, serologic, and histologic characteristics in pediatric nonalcoholic steatohepatitis. Twenty-five pediatric nonalcoholic steatohepatitis liver biopsies were evaluated by immunohistochemistry for presence of activated caspase-3 and cleaved cytokeratin-18. Biopsy specimens were semiquantitatively graded for activity (steatosis, inflammation, and ballooning) and fibrosis. Records were reviewed for serum aspartate aminotransferase, alanine aminotransferase, cholesterol, triglycerides, and body mass index, which was elevated in 92% of cases. Serum aspartate aminotransferase and alanine aminotransferase were elevated in 32% and 68% of cases, respectively. Sixty percent of biopsies exhibited lobular steatosis grade 3, 84% lobular inflammatory activity grade 1, 72% ballooning grade 1, and 76% fibrosis stage 3. Cleaved cytokeratin-18 was associated with milder fibrosis (P = .02) and inflammation (P = .07), although there was no association with steatosis grade. Activated caspase-3 detection was also associated with low inflammatory grade (P = .03) but not with fibrosis and steatosis. This study reveals interesting differential features concerning nonalcoholic steatohepatitis histologic characteristics and apoptosis markers compared with adult cases. Because, in this pediatric series, apoptosis seemed to be an early event in the cascade of liver injury steps, it would be useful to consider caspase inhibitors as potential therapeutic strategies to prevent liver damage progression.
authors: Laboratory of Molecular Biology, Pathology Division, Ricardo Gutiérrez Children Hospital, C1425EFD Buenos Aires, Argentina. valvapamela@yahoo.com
authors: Pamela
authors: P
authors: Valva
authors: Elena
authors: E
authors: De Matteo
authors: Marcela
authors: M
authors: Galoppo
authors: Alejandra
authors: A
authors: Pedreira
authors: Gisela
authors: G
authors: Giacove
authors: Carol
authors: C
authors: Lezama
authors: Irene
authors: I
authors: Marco
authors: Maria C
authors: MC
authors: Galoppo
authors: Maria V
authors: MV
authors: Preciado
mesh_terms: D000293:Adolescent; D000410:Alanine Transaminase / Q000097:blood; D017209:Apoptosis; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D053148:Caspase 3 / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005234:Fatty Liver / Q000145:classification / Q000378:metabolism / Q000473:pathology*; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007223:Infant; D053538:Keratin-18 / Q000378:metabolism*; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008111:Liver Function Tests; D008297:Male
chemical_list: D015415:Biomarkers; D053538:Keratin-18; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D053148:Caspase 3