Studies On Diagnostic Markers And Risk Of NOTCH2 Mutations For Biliary Atresia

Biliary atresia is one of the most serious hepatobiliary diseases in pediatric surgery.It is also the main liver disease that causes neonatal death.Its pathological features are progressive aggravation of inflammation of bile ducts inside and outside the liver and formation of fibrous obstruction,resulting in obstruction of bile drainage in the bile duct,and even progressive fibrosis and cirrhosis of the liver,which eventually lead to liver failure.If not treated in time,the patients usually die around the age of one.The only way to cure biliary atresia is taking surgery,including Kasai operation and liver transplantation.The main procedure of Kasai’s operation is to strip the fibrous tissue of the porta hepatis to provide direct connection with the intrahepatic ductule system to allow bile drainage.However,a percentage of infants still have progressive cirrhosis after Kasai operation,and about 67% of them need liver transplantation.Therefore,liver transplantation is the only effective treatment for congenital biliary atresia in the end stage.Early diagnosis and treatment of biliary atresia can significantly improve the survival rate of patients,but currently the diagnosis of biliary atresia is difficult and often leading to misdiagnosis.Children with biliary atresia are usually born without abnormalities,and gradually show jaundice symptoms 2-3 weeks after birth.In some cases,jaundice occurs several days after birth and is misdiagnosed as physiological jaundice.The main manifestations of blood tests are elevated serum bilirubin,which is easily misdiagnosed as neonatal hepatitis.Cholangiography and laparotomy must be performed to make the final diagnosis.New blood biochemical indicators will be helpful in the diagnosis of biliary atresia.This study studied the plasma AFP protein level in children with biliary atresia.It was found that the plasma AFP level in children with biliary atresia was significantly higher than that in normal infants.Based on AFP and other blood biochemical indicators,a diagnostic model was established to distinguish biliary atresia.The AUC of lock and neonatal hepatitis reached 0.939,which can provide a strong basis for early diagnosis of biliary atresia.Currently,the cause of biliary atresia is not clear.The existing theories include genetics,viral infection and immunological abnormality.In epidemiological studies,it has been found that the incidence of biliary atresia is significantly different among regions and populations.The incidence of biliary atresia in Asians is significantly higher than that in Europeans.On the other hand,pathological study found that there were abnormal proliferation of small bile ducts and abnormal morphology of common bile duct cells in the liver of children with biliary atresia.And biliary atresia is often accompanied by congenital heart malformation.A series of evidences indicate that biliary atresia is not caused by a single factor,and genetic factors may play an important role in this disease.According to previous studies,we believe that biliary atresia should be a complex hereditary disease.In this study,NOTCH2 gene,which plays an important role in hepatobiliary development,was studied by amplifier sequencing.Rare mutations of NOTCH2 gene were found in some children with biliary atresia.It was speculated that NOTCH2 gene might be related to the occurrence of biliary atresia.This study will provide some reference for the etiology and prenatal diagnosis of biliary atresia.