Histamine is correlated with liver fibrosis in biliary atresia

Background and aims: 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. (C) 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.