Background and Aims:The aim was to determine if liver biochemistry indices can be used as biomarkers to help differentiate patients with neonatal Dubin–Johnson syndrome(nDJS)from those with biliary atresia(BA).Method...Background and Aims:The aim was to determine if liver biochemistry indices can be used as biomarkers to help differentiate patients with neonatal Dubin–Johnson syndrome(nDJS)from those with biliary atresia(BA).Methods:Patients with genetically-confirmed nDJS or cholangiographically confirmed BA were retrospectively enrolled and randomly assigned to discovery or verification cohorts.Their liver chemistries,measured during the neonatal period,were compared.Predictive values were calculated by receiver operating characteristic curve analysis.Results:A cohort of 53 nDJS patients was recruited,of whom 13 presented with acholic stools,and 14 underwent diagnostic cholangiography or needle liver biopsy to differentiate from BA.Thirty-five patients in the cohort,with complete biochemical information measured during the neonatal period,were compared with 133 infants with cholangiographically confirmed BA.Total and direct bilirubin,alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bile acids,alkaline phosphatase,and gamma-glutamyl transferase were significantly lower in nDJS than in BA.In the discovery cohort,the areas under the curve for ALT and AST were 0.908 and 0.943,respectively.In the validation cohort,13/15 patients in the nDJS group were classified as nDJS,and 10/53 in the BA control group were positive(p<0.00001)with an ALT biomarker cutoff value of 75 IU/L.Thirteen of 15 patients were classified as nDJS and none were classified positive in the BA group(13/15 vs.0/53,p<0.00001)with an AST cutoff of 87 IU/L.Conclusions:Having assembled and investigated the largest cohort of nDJS patients reported to date,we found that nDJS patients could be distinguished from BA patients using the serum AST level as a biomarker.The finding may be clinically useful to spare cholestatic nDJS patients unnecessary invasive procedures.展开更多
基金funded by the National Natural Science Foundation of China,Grants Number 81873543 and 82171853 (to JSW)supported by the Shanghai Sailing Program (20YF1402900 to TL)+3 种基金Chan-Xue Yan Program of Fudan University (FDEKCXY17 to TL)Canadian Institutes of Health Research (to VL&RW)support from The Metabolomics Innovation Center through the Genome Innovations Network,and from Genome Canada,Genome BC,and Genome Alberta for operations (205MET and 7203)technology development (215MET and MC3T).
文摘Background and Aims:The aim was to determine if liver biochemistry indices can be used as biomarkers to help differentiate patients with neonatal Dubin–Johnson syndrome(nDJS)from those with biliary atresia(BA).Methods:Patients with genetically-confirmed nDJS or cholangiographically confirmed BA were retrospectively enrolled and randomly assigned to discovery or verification cohorts.Their liver chemistries,measured during the neonatal period,were compared.Predictive values were calculated by receiver operating characteristic curve analysis.Results:A cohort of 53 nDJS patients was recruited,of whom 13 presented with acholic stools,and 14 underwent diagnostic cholangiography or needle liver biopsy to differentiate from BA.Thirty-five patients in the cohort,with complete biochemical information measured during the neonatal period,were compared with 133 infants with cholangiographically confirmed BA.Total and direct bilirubin,alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bile acids,alkaline phosphatase,and gamma-glutamyl transferase were significantly lower in nDJS than in BA.In the discovery cohort,the areas under the curve for ALT and AST were 0.908 and 0.943,respectively.In the validation cohort,13/15 patients in the nDJS group were classified as nDJS,and 10/53 in the BA control group were positive(p<0.00001)with an ALT biomarker cutoff value of 75 IU/L.Thirteen of 15 patients were classified as nDJS and none were classified positive in the BA group(13/15 vs.0/53,p<0.00001)with an AST cutoff of 87 IU/L.Conclusions:Having assembled and investigated the largest cohort of nDJS patients reported to date,we found that nDJS patients could be distinguished from BA patients using the serum AST level as a biomarker.The finding may be clinically useful to spare cholestatic nDJS patients unnecessary invasive procedures.
