title: Markers of activated inflammatory cells correlate with severity of liver             damage in children with nonalcoholic fatty liver disease.
abstract: Concomitantly to the obesity epidemic, nonalcoholic fatty liver disease (NAFLD) has become the leading cause of liver disease in children. NAFLD encompasses a spectrum of histological damage ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), with possible progression to cirrhosis. There is growing evidence that the immune system plays a pivotal role in the initiation and progression to NASH but the cellular nature of the hepatic inflammation is still unknown. The present study includes 34 children with biopsy-proven NAFLD. Liver damage was evaluated by the NAFLD activity score (NAS), and the inflammatory infiltrate was characterized by immunohistochemistry for CD45, CD3 and CD163 which are markers of leukocytes, T cells and activated Kupffer cells/macrophages, respectively. Our results have shown that CD45+ (P<0.0001) and CD163+ (P<0.0001) cells were markedly increased in children with severe histological activity (NAS≥5) compared to children with lower activity (NAS<5), whereas CD3+ cells were significantly lower (P<0.01) in children with severe histological activity. There was a significant association between the numbers of CD45+, CD3+ and CD163+ cells, regarding both the portal tract and liver lobule, and the severity of steatosis, ballooning and fibrosis (P<0.01). These data suggest that the severity and composition of the inflammatory infiltrate correlate with steatosis and the severity of disease in children with NAFLD. Moreover, a decrease in CD3+ cells may be involved in the pathogenesis of liver damage. Future studies should evaluate whether it can predict the progression of liver disease independently of established histological scores.
authors.affiliation: Unit of Pathology, IRCCS, Rome, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: De Vito
authors.forename: Anna
authors.initials: A
authors.lastname: Alisi
authors.forename: Andrea
authors.initials: A
authors.lastname: Masotti
authors.forename: Sara
authors.initials: S
authors.lastname: Ceccarelli
authors.forename: Nadia
authors.initials: N
authors.lastname: Panera
authors.forename: Arianna
authors.initials: A
authors.lastname: Citti
authors.forename: Michele
authors.initials: M
authors.lastname: Salata
authors.forename: Luca
authors.initials: L
authors.lastname: Valenti
authors.forename: Ariel E
authors.initials: AE
authors.lastname: Feldstein
authors.forename: Valerio
authors.initials: V
authors.lastname: Nobili
mesh_terms: D000293:Adolescent; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D015415:Biomarkers; D017252:CD3 Complex / Q000032:analysis; D002648:Child; D005234:Fatty Liver / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D007249:Inflammation; D017493:Leukocyte Common Antigens / Q000032:analysis; D008099:Liver / Q000276:immunology* / Q000473:pathology*; D008103:Liver Cirrhosis / Q000473:pathology; D008297:Male; D055611:Natural Killer T-Cells / Q000276:immunology; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity; D011956:Receptors, Cell Surface / Q000032:analysis; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D000098902:CD163 Antigen; D017252:CD3 Complex; D011956:Receptors, Cell Surface; D017493:Leukocyte Common Antigens