Does Sirtuin 1 have a Role in Neonatal Cholestasis of Egyptian Pediatric Patients?

Objectives: To evaluate the role of Silent Information Regulator Sirtuin 1 (SIRT1) in neonatal cholestasis (NC). Background: The incidence of NC is around 1 in 2500 live births. Cholestasis is frequently classified as intrahepatic (involving hepatocytes, bile canaliculi, or intrahepatic bile ducts) or extrahepatic (affecting extrahepatic ducts, common hepatic duct or common bile duct). SIRT1 modulates the farnesoid X receptor (FXR) to regulate bile acid metabolism and liver regeneration. Methods: This retrospective study was conducted on liver biopsy from 74 patients who presented with NC. SIRT1 immunohistochemical expression was evaluated in hepatocytes and the biliary epithelium. Results: A significant association between intrahepatic NC and the overexpression of SIRT1 in hepatocytes zone II was noted (P=0.04). Intrahepatic NC showed a significant association between the overexpression of SIRT1 in hepatocytes and a mild degree of fibrosis (P=0.042). However, extrahepatic NC showed a significant association between overexpression of SIRT1 in the biliary epithelium and the absence of bile duct proliferation and the presence of extramedullary hematopoiesis (P=0.031 and P=0.039 respectively). Conclusion: SIRT1 has a role in the pathogenesis of Egyptian pediatric NC. That could open the gate for new treatment modalities.