Tags

Type your tag names separated by a space and hit enter

Fenofibrate Improves Liver Function and Reduces the Toxicity of the Bile Acid Pool in Patients With Primary Biliary Cholangitis and Primary Sclerosing Cholangitis Who Are Partial Responders to Ursodiol.
Clin Pharmacol Ther. 2020 Jun 01 [Online ahead of print]CP

Abstract

Cholestatic liver diseases result in the hepatic retention of bile acids, causing subsequent liver toxicity. Peroxisome proliferator-activated receptor alpha (PPARα) regulates bile acid metabolism. In this retrospective observational study, we assessed the effects of fenofibrate (a PPARα agonist) therapy on bile acid metabolism when given to patients with primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) who have had an incomplete response to Ursodiol monotherapy. When fenofibrate was added to Ursodiol therapy there was a significant reduction and in some cases normalization of serum alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase abnormalities, as well as pro-inflammatory cytokines. Combination fenofibrate treatment also reduced 7α-hydroxy-4-cholesten-3-one (C4), the bile acid precursor, as well as total, primary, and conjugated bile acids. In addition, principal components analysis and heatmap analysis show that bile acid metabolites trended closer to that of healthy control subjects. These favorable effects of fenofibrate on bile acid metabolism may contribute to its beneficial clinical effects in patients with PBC and PSC experiencing a subtherapeutic response to Ursodiol monotherapy.

Authors+Show Affiliations

Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, Rhode Island, USA.Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, Rhode Island, USA.RI-INBRE Bioinformatics Core, University of Rhode Island, Kingston, Rhode Island, USA.Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, Rhode Island, USA.Liver Center, Yale University School of Medicine, New Haven, Connecticut, USA.Liver Center, Yale University School of Medicine, New Haven, Connecticut, USA.Liver Center, Yale University School of Medicine, New Haven, Connecticut, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32480421

Citation

Ghonem, Nisanne S., et al. "Fenofibrate Improves Liver Function and Reduces the Toxicity of the Bile Acid Pool in Patients With Primary Biliary Cholangitis and Primary Sclerosing Cholangitis Who Are Partial Responders to Ursodiol." Clinical Pharmacology and Therapeutics, 2020.
Ghonem NS, Auclair AM, Hemme CL, et al. Fenofibrate Improves Liver Function and Reduces the Toxicity of the Bile Acid Pool in Patients With Primary Biliary Cholangitis and Primary Sclerosing Cholangitis Who Are Partial Responders to Ursodiol. Clin Pharmacol Ther. 2020.
Ghonem, N. S., Auclair, A. M., Hemme, C. L., Gallucci, G. M., de la Rosa Rodriguez, R., Boyer, J. L., & Assis, D. N. (2020). Fenofibrate Improves Liver Function and Reduces the Toxicity of the Bile Acid Pool in Patients With Primary Biliary Cholangitis and Primary Sclerosing Cholangitis Who Are Partial Responders to Ursodiol. Clinical Pharmacology and Therapeutics. https://doi.org/10.1002/cpt.1930
Ghonem NS, et al. Fenofibrate Improves Liver Function and Reduces the Toxicity of the Bile Acid Pool in Patients With Primary Biliary Cholangitis and Primary Sclerosing Cholangitis Who Are Partial Responders to Ursodiol. Clin Pharmacol Ther. 2020 Jun 1; PubMed PMID: 32480421.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fenofibrate Improves Liver Function and Reduces the Toxicity of the Bile Acid Pool in Patients With Primary Biliary Cholangitis and Primary Sclerosing Cholangitis Who Are Partial Responders to Ursodiol. AU - Ghonem,Nisanne S, AU - Auclair,Adam M, AU - Hemme,Christopher L, AU - Gallucci,Gina M, AU - de la Rosa Rodriguez,Randolph, AU - Boyer,James L, AU - Assis,David N, Y1 - 2020/06/01/ PY - 2019/09/18/received PY - 2020/05/07/accepted PY - 2020/6/2/pubmed PY - 2020/6/2/medline PY - 2020/6/2/entrez JF - Clinical pharmacology and therapeutics JO - Clin. Pharmacol. Ther. N2 - Cholestatic liver diseases result in the hepatic retention of bile acids, causing subsequent liver toxicity. Peroxisome proliferator-activated receptor alpha (PPARα) regulates bile acid metabolism. In this retrospective observational study, we assessed the effects of fenofibrate (a PPARα agonist) therapy on bile acid metabolism when given to patients with primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) who have had an incomplete response to Ursodiol monotherapy. When fenofibrate was added to Ursodiol therapy there was a significant reduction and in some cases normalization of serum alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase abnormalities, as well as pro-inflammatory cytokines. Combination fenofibrate treatment also reduced 7α-hydroxy-4-cholesten-3-one (C4), the bile acid precursor, as well as total, primary, and conjugated bile acids. In addition, principal components analysis and heatmap analysis show that bile acid metabolites trended closer to that of healthy control subjects. These favorable effects of fenofibrate on bile acid metabolism may contribute to its beneficial clinical effects in patients with PBC and PSC experiencing a subtherapeutic response to Ursodiol monotherapy. SN - 1532-6535 UR - https://www.unboundmedicine.com/medline/citation/32480421/Fenofibrate_improves_liver_function_and_reduces_the_toxicity_of_the_bile_acid_pool_in_patients_with_primary_biliary_cholangitis_and_primary_sclerosing_cholangitis_who_are_partial_responders_to_Ursodiol L2 - https://doi.org/10.1002/cpt.1930 DB - PRIME DP - Unbound Medicine ER -
Try the Free App:
Prime PubMed app for iOS iPhone iPad
Prime PubMed app for Android
Prime PubMed is provided
free to individuals by:
Unbound Medicine.