Immunohistochemical Expression of HLA Classes I and II in Neonatal Cholestatic Liver Disease

Neonatal cholestasis (NC) is a significant clinical condition involving hepatobiliary dysfunction, often accompanied by immunological alterations regardless of etiology. Human leukocyte antigens (HLA) molecules, particularly classes I and II, play roles in autoimmune liver diseases. Previous studies showed inconsistent results regarding their expression in hepatocytes and cholangiocytes under normal and pathological conditions. This study aimed to evaluate immunohistochemical expression of HLA I and II in NC.

A retrospective analysis included 45 pediatric NC cases: 27 with biliary atresia (BA), 13 with progressive familial intrahepatic cholestasis (PFIC), and 5 with idiopathic neonatal hepatitis (INH). Twenty normal liver samples from adult transplant donors served as controls. Immunohistochemistry was used to evaluate HLA I and II expression in hepatocytes and cholangiocytes.

Control livers lacked detectable HLA I and II expression. In NC cases, HLA I was expressed in hepatocytes (84.4%) and all cholangiocytes, while HLA II was expressed in both cell types across all cases. BA cases showed significantly higher cholangiocyte expression of HLA I (p = 0.001) and II (p < 0.001) compared to PFIC and INH. HLA I expression was linked to cholangiocyte proliferation (p = 0.005) and inversely with lobular inflammation (p = 0.027). Strong HLA II expression in hepatocytes correlated with severe portal inflammation (p = 0.048), while in cholangiocytes, to proliferation, neutrophilic cholangitis (p = 0.05), and mild lobular inflammation (p = 0.043).

HLA I and II are upregulated in NC, especially in BA, which correlates with disease severity, suggesting a role in pathogenesis.