Apoptosis involvement in the pathogenesis of Hepatitis C virus (HCV) chronic infection. Comparative analysis of two series of pediatrics and adults patients.

VALVA P; DE MATTEO E; GIACOVE G; GALOPPO MC; GUMA C; PRECIADO MV

Brasil

Congreso; III World Congress of Pediatric Gastroenterology, Hepatology and Nutrition.; 2008

European Society for Paediatric Gastroenterology Hepatology and Nutrition y North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.

Histological evidences suggest apoptosis involvement in HCV chronic infection derived liver damage. Many of the changes in apoptotic cells are due caspases activation. Caspase substrates include cytoskeleton proteins, being cytokeratin-18 (CK18) predominant of hepatocytes. The CK18 cleavage constitutes an early event of apoptosis and contributes to cellular collapse. Our aim was to determine the presence of early apoptosis markers, activated caspase-3 (casp-3a) and caspase-generated CK-18 fragment (M30) in liver biopsies of patients with HCV chronic infection and to relate them to biochemical, virological and histological parameters. Twenty children (median age: 8.5 years [range 1-17 yrs]), 12 adults (median age: 46.5 years [range 35-57 yrs]) and 8 controls (congenital liver fibrosis) were analyzed. Stage of fibrosis (F), hepatitis (H), steatosis, lymphoid follicles and bile duct damage were assessed in liver biopsies. Casp-3a and M30 were evaluated by immunohistochemistry. Results were expressed as n° positive hepatocytes/n° total hepatocytes in 20 high-power fields (1000). In both groups genotype 1 was predominant. ALT values (high ALT: 67% in children vs. 100% in adults) did not show differences between series. Adults? histological profile displayed 8% F1, 42% F2, 33% F3 and 17% cirrhosis; 42% moderate H and 42% severe H, meanwhile in children neither cirrhosis nor severe hepatitis were observed (5% F0, 40% F1, 45% F2 and 10% F3; 40% mild H and 60% moderate H). Casp-3a staining was higher in adult than in children (median: 0.16 vs. 0.05), as well as M30 (median: 0.01 vs. 0.007), but only casp-3a was associated with worse fibrosis stages in children (p=0.01). Steatosis was present in both series, but it was more severe and comprised higher n° cases in adults (92% versus 60%). An association between casp-3a and the severity of steatosis was observed in adults (p= 0.05). Association between apoptosis and histological parameters like hepatitis, lymphoid follicles and bile duct damage was not observed in any group. Controls did show neither M30 nor casp-3a labeling. Apoptosis was linked to HCV infection pathogenesis in both series. In children the virus would be directly involved in apoptosis activation, which in turn would contribute to fibrosis development. Meanwhile, in adults apart from direct virus effect, enhanced oxidative stress induced by steatosis may also play a role in apoptosis activation, reflecting altogether a more severe liver damage.