Obeticholic acid for the treatment of primary biliary cholangitis in adult patients: clinical utility and patient selection

Christopher L Bowlus Division of Gastroenterology and Hepatology, University of California Davis, Davis, CA, USA Abstract: Primary biliary cholangitis (PBC), previously known as primary biliary “cirrhosis”, is a rare autoimmune liver disease characterized by the hallmark autoanti...

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Autor principal:	Bowlus CL
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	Primary biliary cholangitis (PBC) nuclear receptors (NRs) farnesoid X receptor (FXR) bile acid (BA) obeticholic acid (OCA) ursodeoxycholic acid (UDCA) Diseases of the digestive system. Gastroenterology RC799-869
Acceso en línea:	https://doaj.org/article/02b78315543141608ce2fe1b8e43b326
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spelling	oai:doaj.org-article:02b78315543141608ce2fe1b8e43b3262021-12-02T00:59:47ZObeticholic acid for the treatment of primary biliary cholangitis in adult patients: clinical utility and patient selection1179-1535https://doaj.org/article/02b78315543141608ce2fe1b8e43b3262016-09-01T00:00:00Zhttps://www.dovepress.com/obeticholic-acid-for-the-treatment-of-primary-biliary-cholangitis-in-a-peer-reviewed-article-HMERhttps://doaj.org/toc/1179-1535Christopher L Bowlus Division of Gastroenterology and Hepatology, University of California Davis, Davis, CA, USA Abstract: Primary biliary cholangitis (PBC), previously known as primary biliary “cirrhosis”, is a rare autoimmune liver disease characterized by the hallmark autoantibodies to mitochondrial antigens and immune-mediated destruction of small bile duct epithelial cells leading to cholestasis and cirrhosis. Surprisingly, while immune modulators have not been effective in the treatment of PBC, supplementation with the hydrophilic bile acid (BA) ursodeoxycholic acid (UDCA) has been demonstrated to slow the disease progression. However, a significant minority of PBC patients do not have a complete response to UDCA and remain at risk of continued disease progression. Although the mechanisms of action are not well understood, UDCA provided proof of concept for BA therapy in PBC. Obeticholic acid (OCA), a novel derivative of the human BA chenodeoxycholic acid, is a potent agonist of the nuclear hormone receptor farnesoid X receptor, which regulates BA synthesis and transport. A series of clinical trials of OCA in PBC, primarily in combination with UDCA, have established that OCA leads to significant reductions in serum alkaline phosphatase that are predicted to lead to improved clinical outcomes, while dose-dependent pruritus has been the most common adverse effect. On the basis of these studies, OCA was given conditional approval by the US Food and Drug Administration with plans to establish the long-term clinical efficacy of OCA in patients with advanced PBC. Keywords: primary biliary cholangitis, nuclear receptors, farnesoid X receptor, bile acid, obeticholic acid, ursodeoxycholic acidBowlus CLDove Medical PressarticlePrimary biliary cholangitis (PBC)nuclear receptors (NRs)farnesoid X receptor (FXR)bile acid (BA)obeticholic acid (OCA)ursodeoxycholic acid (UDCA)Diseases of the digestive system. GastroenterologyRC799-869ENHepatic Medicine: Evidence and Research, Vol Volume 8, Pp 89-95 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Primary biliary cholangitis (PBC) nuclear receptors (NRs) farnesoid X receptor (FXR) bile acid (BA) obeticholic acid (OCA) ursodeoxycholic acid (UDCA) Diseases of the digestive system. Gastroenterology RC799-869
spellingShingle	Primary biliary cholangitis (PBC) nuclear receptors (NRs) farnesoid X receptor (FXR) bile acid (BA) obeticholic acid (OCA) ursodeoxycholic acid (UDCA) Diseases of the digestive system. Gastroenterology RC799-869 Bowlus CL Obeticholic acid for the treatment of primary biliary cholangitis in adult patients: clinical utility and patient selection
description	Christopher L Bowlus Division of Gastroenterology and Hepatology, University of California Davis, Davis, CA, USA Abstract: Primary biliary cholangitis (PBC), previously known as primary biliary “cirrhosis”, is a rare autoimmune liver disease characterized by the hallmark autoantibodies to mitochondrial antigens and immune-mediated destruction of small bile duct epithelial cells leading to cholestasis and cirrhosis. Surprisingly, while immune modulators have not been effective in the treatment of PBC, supplementation with the hydrophilic bile acid (BA) ursodeoxycholic acid (UDCA) has been demonstrated to slow the disease progression. However, a significant minority of PBC patients do not have a complete response to UDCA and remain at risk of continued disease progression. Although the mechanisms of action are not well understood, UDCA provided proof of concept for BA therapy in PBC. Obeticholic acid (OCA), a novel derivative of the human BA chenodeoxycholic acid, is a potent agonist of the nuclear hormone receptor farnesoid X receptor, which regulates BA synthesis and transport. A series of clinical trials of OCA in PBC, primarily in combination with UDCA, have established that OCA leads to significant reductions in serum alkaline phosphatase that are predicted to lead to improved clinical outcomes, while dose-dependent pruritus has been the most common adverse effect. On the basis of these studies, OCA was given conditional approval by the US Food and Drug Administration with plans to establish the long-term clinical efficacy of OCA in patients with advanced PBC. Keywords: primary biliary cholangitis, nuclear receptors, farnesoid X receptor, bile acid, obeticholic acid, ursodeoxycholic acid
format	article
author	Bowlus CL
author_facet	Bowlus CL
author_sort	Bowlus CL
title	Obeticholic acid for the treatment of primary biliary cholangitis in adult patients: clinical utility and patient selection
title_short	Obeticholic acid for the treatment of primary biliary cholangitis in adult patients: clinical utility and patient selection
title_full	Obeticholic acid for the treatment of primary biliary cholangitis in adult patients: clinical utility and patient selection
title_fullStr	Obeticholic acid for the treatment of primary biliary cholangitis in adult patients: clinical utility and patient selection
title_full_unstemmed	Obeticholic acid for the treatment of primary biliary cholangitis in adult patients: clinical utility and patient selection
title_sort	obeticholic acid for the treatment of primary biliary cholangitis in adult patients: clinical utility and patient selection
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/02b78315543141608ce2fe1b8e43b326
work_keys_str_mv	AT bowluscl obeticholicacidforthetreatmentofprimarybiliarycholangitisinadultpatientsclinicalutilityandpatientselection
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Obeticholic acid for the treatment of primary biliary cholangitis in adult patients: clinical utility and patient selection

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