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.