Apoptosis markers in liver biopsy of non-alcoholic steatohepatitis in pediatric patients.

VALVA P; DE MATTEO E; GALOPPO M; PEDREIRA A; GIACOVE G; LEZAMA C; MARCO I; GALOPPO M.C; PRECIADO MV

HUMAN PATHOLOGY

Elsevier

Año: 2008 vol. 39 p. 1816 - 1822

0046-8177

The natural history of pediatric non-alcoholic steatohepatitis is still unknown, however there are differences between adult and pediatric presentation. Apoptosis may play an important role in pathophysiological 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, serological and histological characteristics in pediatric non-alcoholic steatohepatitis. Twenty five pediatric non-alcoholic steatohepatitis liver biopsies were evaluated by immunohistochemistry for presence of activated caspase-3 and cleaved cytokeratin-18. Biopsy specimens were semi-quantitatively graded for activity (steatosis, inflammation and ballooning) and fibrosis. Records were reviewed for serum AST, ALT, cholesterol, triglycerides and body mass index. The last one was elevated in 92% cases. Serum AST and ALT were elevated in 32% and 68% 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 = 0.02) and inflammation (p= 0.07), meanwhile there was no association with steatosis grade. Activated caspase-3 detection was also associated with low inflammatory grade (p = 0.03) but not with fibrosis and steatosis. This study reveals interesting differential features concerning non-alcoholic steatohepatitis histological characteristics and apoptosis markers compared with previous adult reports. Since 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.