Plasma fetal bile acids 7α-hydroxy-3-oxochol-4-en-24-oic acid and 3-oxachola-4,6-dien-24-oic acid indicate severity of liver cirrhosis

Abstract Two 3-oxo-Δ4 fetal bile acids, 3-oxachola-4,6-dien-24-oic acid (1) and 7α-hydroxy-3-oxochol-4-en-24-oic acid (2), occur normally in the human fetus but remain elevated in neonates and children with severe cholestatic liver disease due to an autosomal recessive inborn error of metabolism aff...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Tudor Mocan, Dong Wook Kang, Billy J. Molloy, Hyeonho Jeon, Zeno A. Spârchez, Diren Beyoğlu, Jeffrey R. Idle
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/633c4a068637462d9ae0786632ba2dc0
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:633c4a068637462d9ae0786632ba2dc0
record_format	dspace
spelling	oai:doaj.org-article:633c4a068637462d9ae0786632ba2dc02021-12-02T15:51:13ZPlasma fetal bile acids 7α-hydroxy-3-oxochol-4-en-24-oic acid and 3-oxachola-4,6-dien-24-oic acid indicate severity of liver cirrhosis10.1038/s41598-021-87921-52045-2322https://doaj.org/article/633c4a068637462d9ae0786632ba2dc02021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87921-5https://doaj.org/toc/2045-2322Abstract Two 3-oxo-Δ4 fetal bile acids, 3-oxachola-4,6-dien-24-oic acid (1) and 7α-hydroxy-3-oxochol-4-en-24-oic acid (2), occur normally in the human fetus but remain elevated in neonates and children with severe cholestatic liver disease due to an autosomal recessive inborn error of metabolism affecting Δ4-3-oxo-steroid 5β-reductase (AKR1D1). Relatively little is known about 1 and 2 in adult patients with liver disease. The chemical synthesis of 1 and 2 is therefore described and their quantitation in plasma by ultrarapid chromatography-triple quadrupole mass spectrometry. Plasma concentrations of 1 and 2 were investigated in 25 adult patients with varying degrees of liver cirrhosis with and without hepatocellular carcinoma (HCC). Highly statistically significant correlations (P < 0.0001) were found between severity of liver cirrhosis, determined by the Child–Pugh and MELD scores, with plasma 1 and 2 concentrations, both alone and combined. The presence of HCC did not influence these correlations. Plasma cholic, chenodeoxycholic, deoxycholic, lithocholic or ursodeoxycholic acids, free and as their glycine or taurine conjugates, did not correlate with Child–Pugh or MELD score when corrected for multiple comparisons. These findings demonstrate that plasma levels of fetal bile acids 3-oxachola-4,6-dien-24-oic acid and 7α-hydroxy-3-oxochol-4-en-24-oic acid and likely deteriorating AKR1D1 activity indicate the severity of liver cirrhosis measured by the Child–Pugh and MELD scores.Tudor MocanDong Wook KangBilly J. MolloyHyeonho JeonZeno A. SpârchezDiren BeyoğluJeffrey R. IdleNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tudor Mocan Dong Wook Kang Billy J. Molloy Hyeonho Jeon Zeno A. Spârchez Diren Beyoğlu Jeffrey R. Idle Plasma fetal bile acids 7α-hydroxy-3-oxochol-4-en-24-oic acid and 3-oxachola-4,6-dien-24-oic acid indicate severity of liver cirrhosis
description	Abstract Two 3-oxo-Δ4 fetal bile acids, 3-oxachola-4,6-dien-24-oic acid (1) and 7α-hydroxy-3-oxochol-4-en-24-oic acid (2), occur normally in the human fetus but remain elevated in neonates and children with severe cholestatic liver disease due to an autosomal recessive inborn error of metabolism affecting Δ4-3-oxo-steroid 5β-reductase (AKR1D1). Relatively little is known about 1 and 2 in adult patients with liver disease. The chemical synthesis of 1 and 2 is therefore described and their quantitation in plasma by ultrarapid chromatography-triple quadrupole mass spectrometry. Plasma concentrations of 1 and 2 were investigated in 25 adult patients with varying degrees of liver cirrhosis with and without hepatocellular carcinoma (HCC). Highly statistically significant correlations (P < 0.0001) were found between severity of liver cirrhosis, determined by the Child–Pugh and MELD scores, with plasma 1 and 2 concentrations, both alone and combined. The presence of HCC did not influence these correlations. Plasma cholic, chenodeoxycholic, deoxycholic, lithocholic or ursodeoxycholic acids, free and as their glycine or taurine conjugates, did not correlate with Child–Pugh or MELD score when corrected for multiple comparisons. These findings demonstrate that plasma levels of fetal bile acids 3-oxachola-4,6-dien-24-oic acid and 7α-hydroxy-3-oxochol-4-en-24-oic acid and likely deteriorating AKR1D1 activity indicate the severity of liver cirrhosis measured by the Child–Pugh and MELD scores.
format	article
author	Tudor Mocan Dong Wook Kang Billy J. Molloy Hyeonho Jeon Zeno A. Spârchez Diren Beyoğlu Jeffrey R. Idle
author_facet	Tudor Mocan Dong Wook Kang Billy J. Molloy Hyeonho Jeon Zeno A. Spârchez Diren Beyoğlu Jeffrey R. Idle
author_sort	Tudor Mocan
title	Plasma fetal bile acids 7α-hydroxy-3-oxochol-4-en-24-oic acid and 3-oxachola-4,6-dien-24-oic acid indicate severity of liver cirrhosis
title_short	Plasma fetal bile acids 7α-hydroxy-3-oxochol-4-en-24-oic acid and 3-oxachola-4,6-dien-24-oic acid indicate severity of liver cirrhosis
title_full	Plasma fetal bile acids 7α-hydroxy-3-oxochol-4-en-24-oic acid and 3-oxachola-4,6-dien-24-oic acid indicate severity of liver cirrhosis
title_fullStr	Plasma fetal bile acids 7α-hydroxy-3-oxochol-4-en-24-oic acid and 3-oxachola-4,6-dien-24-oic acid indicate severity of liver cirrhosis
title_full_unstemmed	Plasma fetal bile acids 7α-hydroxy-3-oxochol-4-en-24-oic acid and 3-oxachola-4,6-dien-24-oic acid indicate severity of liver cirrhosis
title_sort	plasma fetal bile acids 7α-hydroxy-3-oxochol-4-en-24-oic acid and 3-oxachola-4,6-dien-24-oic acid indicate severity of liver cirrhosis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/633c4a068637462d9ae0786632ba2dc0
work_keys_str_mv	AT tudormocan plasmafetalbileacids7ahydroxy3oxochol4en24oicacidand3oxachola46dien24oicacidindicateseverityoflivercirrhosis AT dongwookkang plasmafetalbileacids7ahydroxy3oxochol4en24oicacidand3oxachola46dien24oicacidindicateseverityoflivercirrhosis AT billyjmolloy plasmafetalbileacids7ahydroxy3oxochol4en24oicacidand3oxachola46dien24oicacidindicateseverityoflivercirrhosis AT hyeonhojeon plasmafetalbileacids7ahydroxy3oxochol4en24oicacidand3oxachola46dien24oicacidindicateseverityoflivercirrhosis AT zenoasparchez plasmafetalbileacids7ahydroxy3oxochol4en24oicacidand3oxachola46dien24oicacidindicateseverityoflivercirrhosis AT direnbeyoglu plasmafetalbileacids7ahydroxy3oxochol4en24oicacidand3oxachola46dien24oicacidindicateseverityoflivercirrhosis AT jeffreyridle plasmafetalbileacids7ahydroxy3oxochol4en24oicacidand3oxachola46dien24oicacidindicateseverityoflivercirrhosis
_version_	1718385635636543488

Plasma fetal bile acids 7α-hydroxy-3-oxochol-4-en-24-oic acid and 3-oxachola-4,6-dien-24-oic acid indicate severity of liver cirrhosis

Ejemplares similares