Distinctive intrahepatic characteristics of pediatric and adult pathogenesis of chronic hepatitis C infection

PAMELA VALVA ; MARÍA I GISMONDIA; PAOLA C CASCIATO; MARCELA GALOPPO; CAROL LEZAMA; OMAR GALDAME; ADRIAN GADANO; MARÍA C GALOPPO; EDUARDO MULLEN; ELENA B DE MATTEO; MARÍA V PRECIADO

CLINICAL MICROBIOLOGY AND INFECTION

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2014 vol. 20 p. 998 - 1009

1198-743X

Mechanisms leading to liver damage in chronic hepatitis C (CHC) are being discussed, but both immune system and virus are involved. The aim was to evaluate intrahepatic viral infection, apoptosis as well as portal and periportal/interface infiltrate in pediatric and adult patients to elucidate the pathogenesis of chronic hepatitis C. HCV infected, activated caspase-3+ and TUNEL+ hepatocytes, as well as total, CD4+, CD8+, Foxp3+ and CD20+ lymphocytes infiltrating portal and periportal/interface tracts were evaluated in 27 pediatric and 32 adult liver samples by immunohistochemistry or immunofluorescence. Infected hepatocytes number was higher in pediatric than adult samples (p=0.0078). In children, they correlated with apoptotic hepatocytes (activated caspase-3+ r=0.74, p 0.0001; TUNEL+ r=0.606, p=0.0017). Besides, infected (p=0.026) and apoptotic hepatocytes (p=0.03) were associated with fibrosis severity. In adults, activated caspase-3+ cell count was increased in severe hepatitis (p=0.009). Total, CD4+, CD8+ and Foxp3+ lymphocyte count was higher in adult samples (p menor a 0.05). Pediatric CD8+ cells correlated with infected (r=0.495, p=0.04) and TUNEL+ hepatocytes (r=0.474, p=0.047); while adult ones with activated caspase-3+ hepatocytes (r=0.387, p=0.04). In adults, CD8+ was associated with hepatitis severity (p 0.0001) and correlated with inflammatory activity (CD8+ r=0.639, p=0.0003). HCV, apoptosis and immune response proved to be involved in CHC pathogenesis of both pediatric and adult patients. However, liver injury in pediatric CHC would be largely associated with viral cytopathic effect mediated by apoptosis, while in adults would be mainly associated with an exacerbated immune response.