Distinctive intrahepatic characteristics of paediatric and adult pathogenesis of chronic hepatitis C infection. (1st August 2014)

• Record Type: Journal Article
• Authors: Valva, P.; Gismondi, M. I.; Casciato, P. C.; Galoppo, M.; Lezama, C.; Galdame, O.; Gadano, A.; Galoppo, M. C.; Mullen, E.; De Matteo, E. N.; Preciado, M. V.; Antonelli, G.
• Is Part Of: Clinical microbiology and infection. Volume 20:Number 12(2014:Dec.)
• Page Start: O998
• Page End: O1009
• Publication Date: 2014-08-01
• Subjects: Medical microbiology -- Periodicals; Diagnostic microbiology -- Periodicals; Communicable diseases -- Periodicals; Infection -- Periodicals; 616.01
• DOI: 10.1111/1469-0691.12728
• Languages: English
• ISSNs: 1198-743X

Abstract

<abstract abstract-type="main" id="clm12728-abs-0001"> <title>Abstract</title> <p>Mechanisms leading to liver damage in chronic hepatitis C (CHC) are being discussed, but both the immune system and the virus are involved. The aim of this study was to evaluate intrahepatic viral infection, apoptosis and portal and periportal/interface infiltrate in paediatric and adult patients to elucidate the pathogenesis of chronic hepatitis C. HCV‐infected, activated caspase‐3<sup>+</sup> and TUNEL<sup>+</sup> hepatocytes, as well as total, CD4<sup>+</sup>, CD8<sup>+</sup>, Foxp3<sup>+</sup> and CD20<sup>+</sup> lymphocytes infiltrating portal and periportal/interface tracts were evaluated in 27 paediatric and 32 adult liver samples by immunohistochemistry or immunofluorescence. The number of infected hepatocytes was higher in paediatric than in adult samples (p<italic> </italic>0.0078). In children, they correlated with apoptotic hepatocytes (activated caspase‐3<sup>+</sup><italic>r</italic> = 0.74, p<italic> </italic><<italic> </italic>0.0001; TUNEL<sup>+</sup><italic>r</italic> = 0.606, p<italic> </italic>0.0017). Also, infected (p<italic> </italic>=<italic> </italic>0.026) and apoptotic hepatocytes (p<italic> </italic>=<italic> </italic>0.03) were associated with the severity of fibrosis. In adults, activated caspase‐3<sup>+</sup> cell count was increased in severe hepatitis (p<italic> </italic>=<italic> </italic>0.009). Total, CD4<sup>+</sup>, CD8<sup>+</sup> and Foxp3<sup>+</sup> lymphocyte count was higher in adult samples (p<italic> </italic><<italic> </italic>0.05). Paediatric CD8<sup>+</sup> cells correlated with infected (<italic>r</italic> = 0.495, p<italic> </italic>0.04) and TUNEL<sup>+</sup> hepatocytes (<italic>r</italic> = 0.474, p<italic> </italic>=<italic> </italic>0.047), while adult ones correlated with activated caspase‐3<sup>+</sup> hepatocytes (<italic>r</italic> = 0.387, p<italic> </italic>0.04). In adults, CD8<sup>+</sup> was associated with hepatitis severity (p<italic> </italic><<italic> </italic>0.0001) and correlated with inflammatory activity (CD8<sup>+</sup><italic>r</italic> = 0.639, p<italic> </italic>0.0003). HCV, apoptosis and immune response proved to be involved in CHC pathogenesis of both paediatric and adult patients. However, liver injury in paediatric CHC would be largely associated with a viral cytopathic effect mediated by apoptosis, while in adults it would be mainly associated with an exacerbated immune response.</p> </abstract>