title: Histamine is correlated with liver fibrosis in biliary atresia.
abstract: OBJECTIVE
  Biliary atresia (BA) is a severe neonatal cholestasis disease that is caused by obstruction of extra bile ducts. Liver fibrosis progresses dramatically in BA, and the underlying molecular mechanism is largely unknown.
  
  
  METHODS
  Amino acids and biogenic amines were quantified by targeted metabolomic methods in livers of 52 infants with BA and 16 infants with neonatal hepatitis syndrome (NHS). Normal adjacent nontumor liver tissues from 5 hepatoblastoma infants were used as controls. Orthogonal partial least-squares discriminant analysis was used to identify the differences between BA, NHS, and control tissues. Histamine metabolism enzymes and receptors were analyzed by immunohistochemistry and Western blot.
  
  
  RESULTS
  The orthogonal partial least-squares discriminant analysis clearly separated BA from NHS and the controls using amino acid and biogenic amine profiles. Histamine was significantly increased in the livers of BA infants and was positively correlated with the severity of fibrosis. This finding was supported by the elevated l-histidine decarboxylase and reduced monoamine oxidase type B expressions in the BA infants with severe fibrosis. Furthermore, histamine receptor H1 was observed in the cholangiocytes of BA livers.
  
  
  CONCLUSIONS
  Histamine was positively correlated with fibrosis and may be a potential target to prevent liver fibrosis in BA.
authors.affiliation: Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University (SJTU), Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai Institute for Pediatric Research, Shanghai, China.
authors.forename: Kejun
authors.initials: K
authors.lastname: Zhou
authors.affiliation: University of Hawaii Cancer Center, Honolulu, HI, United States.
authors.forename: Guoxiang
authors.initials: G
authors.lastname: Xie
authors.affiliation: Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai Institute for Pediatric Research, Shanghai, 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, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University (SJTU), Shanghai, China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Pan
authors.affiliation: Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University (SJTU), Shanghai, 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, 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, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: University of Hawaii Cancer Center, Honolulu, HI, United States. Electronic address: wjia@cc.hawaii.edu.
authors.forename: Wei
authors.initials: W
authors.lastname: Jia
authors.affiliation: Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University (SJTU), Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai Institute for Pediatric Research, Shanghai, China. Electronic address: caiw1978@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Cai
mesh_terms: D000597:Amino Acids, Branched-Chain / Q000097:blood*; D001656:Biliary Atresia / Q000150:complications*; D016022:Case-Control Studies; D002681:China; D005260:Female; D006505:Hepatitis / Q000150:complications*; D006632:Histamine / Q000032:analysis*; D006801:Humans; D007223:Infant; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000473:pathology*; D008297:Male; D055432:Metabolomics; D015999:Multivariate Analysis
chemical_list: D000597:Amino Acids, Branched-Chain; D006632:Histamine
keywords: Biliary atresia; Fibrosis; Histamine