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Distinct Plasma Bile Acid Profiles of Biliary Atresia and Neonatal Hepatitis Syndrome Kejun Zhou, Jun Wang, Guoxiang Xie, Ying Zhou, Weihui Yan, Weihua Pan, Yanran Che, Ting Zhang, Linda Wong, Sandi Kwee, Yongtao Xiao, Jie Wen, Wei Cai, and Wei Jia J. Proteome Res., Just Accepted Manuscript • DOI: 10.1021/acs.jproteome.5b00676 • Publication Date (Web): 09 Oct 2015 Downloaded from http://pubs.acs.org on October 12, 2015
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Journal of Proteome Research is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.
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Journal of Proteome Research
Distinct Plasma Bile Acid Profiles of Biliary Atresia and Neonatal Hepatitis Syndrome Kejun Zhou,1,2 # Jun Wang,1 # Guoxiang Xie,3,4 Ying Zhou,1 Weihui Yan,2 Weihua Pan,1 Yanran Che,5 Ting Zhang,5 Linda Wong,4 Sandi Kwee,4 Yongtao Xiao,2 Jie Wen,2 Wei Cai,1,2 * Wei Jia,3,4 * 1
Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine,
Shanghai Jiao Tong University (SJTU), Shanghai, China 2
Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition,
Shanghai Institute for Pediatric Research, Shanghai, China 3
Center for Translational Medicine, Six People's Hospital, SJTU School of
Medicine, Shanghai, China 4
University of Hawaii Cancer Center, Honolulu, HI 96813, United States of
America 5
Department of Infection and Gastroenterology, Shanghai Children's Hospital,
SJTU School of Medicine, Shanghai, China #
These authors contributed equally to the work.
* Corresponding author:
Wei Cai. 1665 Kong Jiang Road, Shanghai, China. Tel & Fax: 86-21-65791316. Email:
[email protected] 1
ACS Paragon Plus Environment
Journal of Proteome Research
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Wei Jia. 701 Ilalo Street, Honolulu, Hawaii, USA. Tel & Fax: 01-808-5645823. Email:
[email protected] 2
ACS Paragon Plus Environment
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Journal of Proteome Research
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 non-tumour liver tissues taken from hepatoblastoma patients as controls. Both BA and NHS 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 the plasma TCDCA to CDCA was significantly higher in BA compared to healthy infants (p
