Abstract
Primary biliary cholangitis (PBC) is an autoimmune disease characterized by chronic destruction of the bile ducts. A major unanswered question regarding the pathogenesis of PBC is the precise mechanisms of small bile duct injury. Emperipolesis is one of cell‐in‐cell structures that is a potential histological hallmark associated with chronic hepatitis B. This study aimed to clarify the pathogenesis and characteristics of emperipolesis in PBC liver injury. Sixty‐six PBC patients, diagnosed by liver biopsy combined with laboratory test, were divided into early‐stage PBC (stages I and II, n = 39) and late‐stage PBC (stages III and IV, n = 27). Emperipolesis was measured in liver sections stained with haematoxylin‐eosin. The expressions of CK19, CD3, CD4, CD8, CD20, Ki67 and apoptosis of BECs were evaluated by immunohistochemistry or immunofluorescence double labelling. Emperipolesis was observed in 62.1% of patients with PBC, and BECs were predominantly host cells. The number of infiltrating CD3+ and CD8+ T cells correlated with the advancement of emperipolesis (R 2 = 0.318, P < .001; R 2 = 0.060, P < .05). The cell numbers of TUNEL‐positive BECs and double staining for CK19 and Ki67 showed a significant positive correlation with emperipolesis degree (R 2 = 0.236, P < .001; R 2 = 0.267, P < .001). We conclude that emperipolesis mediated by CD8+ T cells appears to be relevant to apoptosis of BEC and thus may aggravate the further injury of interlobular bile ducts.
Highlights
Primary biliary cholangitis (PBC) is an autoimmune disease characterized by chronic destruction of the bile ducts resulting in cholestasis, portal inflammation and fibrosis that leads to progressive ductopenia and cirrhosis.[1]
Our present study aims to define the role of emperipolesis in bile duct injury in PBC and to identify the cell types entering biliary epithelial cell (BEC) concerning the chronic nonsuppurative destructive cholangitis by analysing the infiltrating cells around the damaged bile duct in PBC patient samples
The main immune cells in liver tissues were CD3+, CD4+, CD8+ lymphocytes, and CD8+ T cells were predominant around the damaged interlobular bile ducts in early stage of PBC
Summary
Primary biliary cholangitis (PBC) is an autoimmune disease characterized by chronic destruction of the bile ducts resulting in cholestasis, portal inflammation and fibrosis that leads to progressive ductopenia and cirrhosis.[1] Orthotopic liver transplantation is to date the only definitive treatment approach for end-stage PBC. A major unanswered question regarding the pathogenesis of PBC is the precise mechanisms of small duct injury and destruction. Several findings suggest that biliary epithelial cell (BEC) apoptosis may be of considerable importance for understanding PBC,[2,3,4] the exact mechanism of cellular destruction remains to be elucidated. Our present study aims to define the role of emperipolesis in bile duct injury in PBC and to identify the cell types entering BEC concerning the chronic nonsuppurative destructive cholangitis by analysing the infiltrating cells around the damaged bile duct in PBC patient samples
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