Hepatic progenitor cells in children with chronic hepatitis C

Abstract

OBJECTIVE: Hepatic progenitor cells (HPCs) are bipotential stem cells that can differentiate towards the hepatocytic and cholangiocytic lineages. Many studies have investigated HPCs in adults with hepatitis C virus infection; however, none has been carried out in the pediatric population. Therefore, this work aimed to investigate HPCs expansion in children with chronic hepatitis C (CHC) and its correlation with histopathology, viremia, and treatment response. PATIENTS AND METHODS: Eighty children with CHC, 73 of whom received interferon-based therapy, were recruited. Sections of their liver biopsies were prepared for immunostaining of HPCs using cytokeratin-7 antibody. RESULTS: HPCs were expanded in most children (81.3%) with CHC. Expansion occurred in two forms: intraparenchymal isolated hepatic progenitor cell form and periportal ductular reaction form. There was a significant increase in HPCs expansion in higher stages of fibrosis (50, 81.8, and 100% in no, mild, and moderate fibrosis, respectively, with P=0.029). Also, HPCs expansion increased with increased grade of necroinflammatory activity (0, 77.8, 81.8, and 100%, in no, minimal, mild, and moderate activity, respectively), although this was statistically insignificant. Moreover, a significant positive correlation was found between the isolated hepatic progenitor cell number and ductular reaction grade (r=0.755, P<0.0001), and both were significantly correlated with the level of viremia and the grade of necroinflammatory activity. Finally, HPCs expansion was not related to the treatment response. CONCLUSION: The relationship of HPCs with both the severity of hepatitis and the stage of fibrosis may be because of a role of HPCs in their pathogenesis.