title: Distinct Plasma Bile Acid Profiles of Biliary Atresia and Neonatal Hepatitis Syndrome.
abstract: Biliary atresia (BA) is a severe chronic cholestasis disorder of infants that leads to death if not treated on time. Neonatal hepatitis syndrome (NHS) is another leading cause of neonatal cholestasis confounding the diagnosis of BA. Recent studies indicate that altered bile acid metabolism is closely associated with liver injury and cholestasis. In this study, we systematically measured the bile acid metabolome in plasma of BA, NHS, and healthy controls. Liver bile acids were also measured using biopsy samples from 48 BA and 16 NHS infants undergoing operative cholangiography as well as 5 normal adjacent nontumor liver tissues taken from hepatoblastoma patients as controls. Both BA and NHS samples had significantly elevated bile acid levels in plasma compared to normal controls. BA patients showed a distinct bile acid profile characterized by the higher taurochenodeoxycholic acid (TCDCA) level and lower chenodeoxycholic acid (CDCA) level than those in NHS patients. The ratio of TCDCA to CDCA in plasma was significantly higher in BA compared to healthy infants (p < 0.001) or NHS (p < 0.001). The area under receiver operating characteristic curve for TCDCA/CDCA to differentiate BA from NHS was 0.923 (95% CI: 0.862-0.984). These findings were supported by significantly altered expression levels of bile acid transporters and nuclear receptors in liver including farnesoid X receptor (FXR), small heterodimer partner (SHP), bile salt export pump (BSEP), and multidrug resistant protein 3 (MDR3) in BA compared to NHS. Taken together, the plasma bile acid profiles are distinct in BA, NHS, and normal infants, as characterized by the ratio of TCDCA/CDCA differentially distributed among the three groups of infants.
authors.affiliation: Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University (SJTU) , Shanghai 200092, China.|Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai Institute for Pediatric Research , Shanghai 200092, China.
authors.forename: Kejun
authors.initials: K
authors.lastname: Zhou
authors.affiliation: Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University (SJTU) , Shanghai 200092, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Center for Translational Medicine, Six People's Hospital, SJTU School of Medicine , Shanghai 200092, China.|University of Hawaii Cancer Center , Honolulu, Hawaii 96813, United States.
authors.forename: Guoxiang
authors.initials: G
authors.lastname: Xie
authors.affiliation: Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University (SJTU) , Shanghai 200092, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai Institute for Pediatric Research , Shanghai 200092, China.
authors.forename: Weihui
authors.initials: W
authors.lastname: Yan
authors.affiliation: Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University (SJTU) , Shanghai 200092, China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Pan
authors.affiliation: Department of Infection and Gastroenterology, Shanghai Children's Hospital, SJTU School of Medicine , Shanghai 200092, China.
authors.forename: Yanran
authors.initials: Y
authors.lastname: Che
authors.affiliation: Department of Infection and Gastroenterology, Shanghai Children's Hospital, SJTU School of Medicine , Shanghai 200092, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: University of Hawaii Cancer Center , Honolulu, Hawaii 96813, United States.
authors.forename: Linda
authors.initials: L
authors.lastname: Wong
authors.affiliation: University of Hawaii Cancer Center , Honolulu, Hawaii 96813, United States.
authors.forename: Sandi
authors.initials: S
authors.lastname: Kwee
authors.affiliation: Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai Institute for Pediatric Research , Shanghai 200092, China.
authors.forename: Yongtao
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai Institute for Pediatric Research , Shanghai 200092, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wen
authors.affiliation: Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University (SJTU) , Shanghai 200092, China.|Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai Institute for Pediatric Research , Shanghai 200092, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cai
authors.affiliation: Center for Translational Medicine, Six People's Hospital, SJTU School of Medicine , Shanghai 200092, China.|University of Hawaii Cancer Center , Honolulu, Hawaii 96813, United States.
authors.forename: Wei
authors.initials: W
authors.lastname: Jia
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000097:blood / Q000235:genetics; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000097:blood / Q000235:genetics; D000410:Alanine Transaminase / Q000097:blood / Q000235:genetics; D019540:Area Under Curve; D001219:Aspartate Aminotransferases / Q000097:blood / Q000235:genetics; D001647:Bile Acids and Salts / Q000097:blood* / Q000145:classification; D001656:Biliary Atresia / Q000097:blood / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D016022:Case-Control Studies; D002635:Chenodeoxycholic Acid / Q000097:blood*; D002758:Cholangiography; D002779:Cholestasis / Q000097:blood / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D005260:Female; D005786:Gene Expression Regulation; D006505:Hepatitis / Q000097:blood / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D055442:Metabolome; D018160:Receptors, Cytoplasmic and Nuclear / Q000097:blood / Q000235:genetics; D013655:Taurochenodeoxycholic Acid / Q000097:blood*; D005723:gamma-Glutamyltransferase / Q000097:blood / Q000235:genetics; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; D000410:Alanine Transaminase; D001219:Aspartate Aminotransferases; D001647:Bile Acids and Salts; D002635:Chenodeoxycholic Acid; D018160:Receptors, Cytoplasmic and Nuclear; D013655:Taurochenodeoxycholic Acid; D005723:gamma-Glutamyltransferase; D000099150:Receptor, Farnesoid X-Activated; C093491:ABCB11 protein, human; C099713:nuclear receptor subfamily 0, group B, member 2; C095122:multidrug resistance protein 3
keywords: TCDCA/CDCA; bile acids; biliary atresia; neonatal hepatitis syndrome