Markers of activated inflammatory cells correlate with severity of liver damage in children with nonalcoholic fatty liver disease

Int J Mol Med. 2012 Jul;30(1):49-56. doi: 10.3892/ijmm.2012.965. Epub 2012 Apr 10.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antigens, CD / analysis
  • Antigens, Differentiation, Myelomonocytic / analysis
  • Biomarkers
  • CD3 Complex / analysis
  • Child
  • Fatty Liver / immunology*
  • Fatty Liver / pathology
  • Female
  • Humans
  • Inflammation
  • Leukocyte Common Antigens / analysis
  • Liver / immunology*
  • Liver / pathology*
  • Liver Cirrhosis / pathology
  • Male
  • Natural Killer T-Cells / immunology
  • Non-alcoholic Fatty Liver Disease
  • Obesity
  • Receptors, Cell Surface / analysis

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Biomarkers
  • CD163 antigen
  • CD3 Complex
  • Receptors, Cell Surface
  • Leukocyte Common Antigens