Peripheral Blood CD177~+ Cells As An Early Diagnostic Marker For Biliary Atresia: A Prospective Multicentre Study In Pediatric Patients With Cholestasis

Background:Biliary atresia(BA)is an extrahepatic and intrahepatic cholangiopathy and induces a rapidly progressive hepatic fibrosis,ultimately,liver failure.BA is difficult to distinguish from other chronic cholestasis in infants and other young children.Thus,new markers for early diagnosis are urgently needed.Our recent result shows that a large number of CD177~+cells infiltrated the intrahepatic portal area in children with BA,and these cells damaged biliary duct in early stage.Thus,this study aims to demonstrate that CD177~+cells can be used as a biomarker for the early diagnosis of BA.Method:In this prospective multicenter study,cholestatic subjects with initial admission were recruited and excluded in the pediatric cholestasis cohort.The proportion of CD177~+cells in peripheral blood was determined by flow cytometry.This study involved a diagnostic cohort for exploring CD177~+cell and a prospective validation study to assess the generalisability and clinical applicability of the system.This marker performances were evaluated using area under the curve(AUC),sensitivity,specificity,accuracy,positive predictive value(PPV),and negative predictive value(NPV).Result:Between Aug 2018,and Apr 2017,153 patients were recruited in the diagnostic cohort.113 eligible cholestatic patients were enrolled in prospective validation cohort1 between Aug 2020 and May 2022,and 69 eligible cholestatic patients were enrolled in prospective validation cohort 2 between Mar 2021 and Mar 2022;The proportion of CD177~+cell had favorable accuracy for the prediction of BA in the diagnostic cohort(AUC 0·9601[95%CI 0·9218–0·9983]),and in validation cohort 1(AUC 0·982[95%CI 0·9004–0·9559])and validation cohort 2(AUC 0·9211[95%CI0·8529–0·9892]).Combined with CD177~+cells and GGT also significantly outperformed single prediction marker(AUC 0.9558[95%CI 0.9319-0.9797])for the proportion of CD177~+cell.For subgroup of less than 45 days,the diagnostic accuracy of CD177~+cell was significantly greater than GGT(AUC 0.9189[95%CI 0.8266-1.000]).Conclusion:The proportion of CD177~+cells in peripheral blood has high sensitivity and specificity for differentiating biliary atresia from other infantile cholestatic diseases,and can be used as a reliable indicator for the early diagnosis of biliary atresia.It has good diagnostic performance for BA diseases,and also maintains good diagnostic ability in patients with age≤45d,which is expected to help early diagnosis of BA in clinical applications.