BACKGROUND/ PURPOSE: Although the precise pathogenesis for the destruction of the intrahepatic biliary tract in a patient with biliary atresia (BA) is still unclear, it is known that progressive destruction of the intrahepatic biliary tract is responsible for poor long-term outcome after surgical treatment. In this study, the authors evaluated the expression of HLA-DR in liver tissue of patients with BA to explore its role in the pathogenesis of this disease. METHODS: Liver biopsy specimens from patients with BA (n = 14) and normal liver biopsies (n = 12) were studied immunohistochemically and were assessed immune electron microscopically to detect the expression of HLA-DR. All patients underwent follow-up for at least 3 months after surgery evaluating the short-term postoperative outcome by monitoring the serum bilirubin level during jaundice persistency. RESULTS: The immunohistochemical examinations showed in 10 of 14 liver specimens in the BA group a positive expression of HLA-DR. This expression was mainly detected in bile ducts of the central portal area rather than in proliferated ones in more peripheral areas. None of the specimens from the control group showed positive expression. Eight of 14 specimens in the BA group showed immunoelectron microscopic depositions of colloidal gold in dull and swollen ductules microvilli. This was not observed in the control group. In patients with BA there was an inverse relationship between short-term postoperative outcome and expression of HLA-DR in intrahepatic ductules. CONCLUSIONS: Our findings show that there is an aberrant expression of HLA-DR in microvilli of the ductules in patients with BA, and this abnormal expression is inversely related to the short-term postoperative outcome. It is suggested that aberrant HLA-DR expression in bile ductules may play a pathogenic role in progressive damage to the intrahepatic bile ducts in BA.
BACKGROUND/ PURPOSE: Although the precise pathogenesis for the destruction of the intrahepatic biliary tract in a patient with biliary atresia (BA) is still unclear, it is known that progressive destruction of the intrahepatic biliary tract is responsible for poor long-term outcome after surgical treatment. In this study, the authors evaluated the expression of HLA-DR in liver tissue of patients with BA to explore its role in the pathogenesis of this disease. METHODS: Liver biopsy specimens from patients with BA (n = 14) and normal liver biopsies (n = 12) were studied immunohistochemically and were assessed immune electron microscopically to detect the expression of HLA-DR. All patients underwent follow-up for at least 3 months after surgery evaluating the short-term postoperative outcome by monitoring the serum bilirubin level during jaundice persistency. RESULTS: The immunohistochemical examinations showed in 10 of 14 liver specimens in the BA group a positive expression of HLA-DR. This expression was mainly detected in bile ducts of the central portal area rather than in proliferated ones in more peripheral areas. None of the specimens from the control group showed positive expression. Eight of 14 specimens in the BA group showed immunoelectron microscopic depositions of colloidal gold in dull and swollen ductules microvilli. This was not observed in the control group. In patients with BA there was an inverse relationship between short-term postoperative outcome and expression of HLA-DR in intrahepatic ductules. CONCLUSIONS: Our findings show that there is an aberrant expression of HLA-DR in microvilli of the ductules in patients with BA, and this abnormal expression is inversely related to the short-term postoperative outcome. It is suggested that aberrant HLA-DR expression in bile ductules may play a pathogenic role in progressive damage to the intrahepatic bile ducts in BA.
Authors: Elisabeth Schrumpf; Corey Tan; Tom H Karlsen; Jon Sponheim; Niklas K Björkström; Olav Sundnes; Kristian Alfsnes; Arthur Kaser; Douglas M Jefferson; Yoshiyuki Ueno; Tor J Eide; Guttorm Haraldsen; Sebastian Zeissig; Mark A Exley; Richard S Blumberg; Espen Melum Journal: Hepatology Date: 2015-05-20 Impact factor: 17.425
Authors: Jorge A Bezerra; Rebecca G Wells; Cara L Mack; Saul J Karpen; Jay H Hoofnagle; Edward Doo; Ronald J Sokol Journal: Hepatology Date: 2018-09 Impact factor: 17.425