2024
PPAR-Mediated Bile Acid Glucuronidation: Therapeutic Targets for the Treatment of Cholestatic Liver Diseases
Gallucci G, Hayes C, Boyer J, Barbier O, Assis D, Ghonem N. PPAR-Mediated Bile Acid Glucuronidation: Therapeutic Targets for the Treatment of Cholestatic Liver Diseases. Cells 2024, 13: 1296. PMID: 39120326, PMCID: PMC11312002, DOI: 10.3390/cells13151296.Peer-Reviewed Original ResearchPrimary biliary cholangitisPrimary sclerosing cholangitisPeroxisome proliferator-activated receptorCholestatic liver diseaseUrsodeoxycholic acidUridine 5'-diphospho-glucuronosyltransferaseObeticholic acidBile acid metabolismAdjunctive therapyIncomplete response to UDCAProgression of primary biliary cholangitisResponse to UDCALiver diseasePeroxisome proliferator-activated receptor agonistsSecond-line treatmentMarkers of cholestasisImpairment of bile flowTherapeutic targetTreatment of cholestatic liver diseasesRetention of bile acidsAlternative treatment strategiesProgression to fibrosisProliferator-activated receptorsAcid metabolismBiliary cholangitis
2023
Human vascularized bile duct-on-a chip: a multi-cellular micro-physiological system for studying cholestatic liver disease
Du Y, de Jong I, Gupta K, Waisbourd-Zinman O, Har-Zahav A, Soroka C, Boyer J, Llewellyn J, Liu C, Naji A, Polacheck W, Wells R. Human vascularized bile duct-on-a chip: a multi-cellular micro-physiological system for studying cholestatic liver disease. Biofabrication 2023, 16: 015004. PMID: 37820623, PMCID: PMC10587873, DOI: 10.1088/1758-5090/ad0261.Peer-Reviewed Original ResearchConceptsCholestatic liver diseasePrimary sclerosing cholangitisLiver diseaseBile ductBile duct tissuesDuct tissuePeripheral blood mononuclear cellsEndothelial cellsBlood mononuclear cellsNormal bile duct tissuesHuman vascular endothelial cellsVascular endothelial cellsPSC patientsSclerosing cholangitisIL-17ATh17 cellsMononuclear cellsVascular channelsBiliary organoidsCholangiocyte organoidsBlood vesselsCholangiocytesDiseaseFlow of bloodTight junctions
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
Ghonem NS, Auclair AM, Hemme CL, Gallucci GM, de la Rosa Rodriguez R, Boyer JL, Assis DN. 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 & Therapeutics 2020, 108: 1213-1223. PMID: 32480421, PMCID: PMC7886378, DOI: 10.1002/cpt.1930.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedBile Acids and SaltsBiomarkersCholangitis, SclerosingCytokinesDrug Therapy, CombinationFemaleFenofibrateHumansInflammation MediatorsLiverLiver Cirrhosis, BiliaryLiver Function TestsMaleMiddle AgedPPAR alphaPrincipal Component AnalysisRetrospective StudiesTreatment OutcomeUrsodeoxycholic AcidYoung AdultConceptsPrimary sclerosing cholangitisPrimary biliary cholangitisBile acid metabolismSclerosing cholangitisBiliary cholangitisBile acidsAcid metabolismPeroxisome proliferator-activated receptor alphaProliferator-activated receptor alphaRetrospective observational studyBeneficial clinical effectsCholestatic liver diseasePro-inflammatory cytokinesBile acid metabolitesHealthy control subjectsBile acid poolSerum alkaline phosphataseAminotransferase abnormalitiesUrsodiol therapyFenofibrate therapyPartial respondersBile acid precursorsClinical effectsFenofibrate treatmentLiver disease
2018
Cenicriviroc, a cytokine receptor antagonist, potentiates all‐trans retinoic acid in reducing liver injury in cholestatic rodents
Yu D, Cai S, Mennone A, Vig P, Boyer JL. Cenicriviroc, a cytokine receptor antagonist, potentiates all‐trans retinoic acid in reducing liver injury in cholestatic rodents. Liver International 2018, 38: 1128-1138. PMID: 29356312, PMCID: PMC6032984, DOI: 10.1111/liv.13698.Peer-Reviewed Original ResearchConceptsBile acid pool sizeTrans retinoic acidAcid pool sizePlasma liver enzymesLiver injurySuperior therapeutic effectLiver necrosisLiver enzymesT cellsTherapeutic effectRetinoic acidAntagonist of CCR2Hepatic inflammatory cellsCholestatic liver injuryBile duct proliferationBody weight ratioCholestatic liver diseasePro-inflammatory cytokinesCytokine receptor antagonistsHepatic hydroxyproline contentExpression of cytokinesDuct-ligated ratsBile acid synthesisHepatic infiltrationLiver disease
2017
Bile acids initiate cholestatic liver injury by triggering a hepatocyte-specific inflammatory response
Cai SY, Ouyang X, Chen Y, Soroka CJ, Wang J, Mennone A, Wang Y, Mehal WZ, Jain D, Boyer JL. Bile acids initiate cholestatic liver injury by triggering a hepatocyte-specific inflammatory response. JCI Insight 2017, 2: e90780. PMID: 28289714, PMCID: PMC5333973, DOI: 10.1172/jci.insight.90780.Peer-Reviewed Original ResearchConceptsLiver injuryInflammatory responseBile acid-induced liver injuryCholestatic liver injuryInflammatory liver injuryProinflammatory cytokine expressionCholestatic liver diseaseBile duct ligationVivo mouse modelHepatic infiltrationInflammatory injurySerum aminotransferasesLiver diseaseCholestatic patientsCytokine expressionChemokine inductionPathophysiologic concentrationsNeutrophil chemotaxisDuct ligationPathophysiologic levelsMouse modelNew therapiesInnate immunityInjuryPeriportal areas
2015
Fibrates and cholestasis
Ghonem NS, Assis DN, Boyer JL. Fibrates and cholestasis. Hepatology 2015, 62: 635-643. PMID: 25678132, PMCID: PMC4515188, DOI: 10.1002/hep.27744.BooksConceptsPrimary sclerosing cholangitisPrimary biliary cirrhosisCholestatic liver diseaseUDCA therapyLiver diseaseUrsodeoxycholic acidNuclear receptorsProgression of PBCHepatic transportersPeroxisome proliferator-activated receptor alphaProliferator-activated receptor alphaToxic bile constituentsApical sodium-dependent bile salt transporterOnly therapeutic optionCholestatic liver disordersBile acid homeostasisBile acid synthesisBile salt transportersMultidrug resistance protein 3Cytochrome P450PPARα effectLiver transplantationSclerosing cholangitisBiliary cirrhosisLiver failure
2010
Cholestasis: Genetic and Acquired
Boyer J. Cholestasis: Genetic and Acquired. Seminars In Liver Disease 2010, 30: 113-115. PMID: 20422493, DOI: 10.1055/s-0030-1253220.Peer-Reviewed Original ResearchConceptsBile salt export pumpCholestatic liver diseaseMultidrug resistance protein 3Cholestatic liver injuryLiver diseaseBile acidsBile salt transportersIssue of SeminarsLiver injuryCholestatic disordersBile flowSulfate conjugatesSodium taurocholate co-transporting polypeptideBile duct-cannulated animalsBile formationExport pumpProtein 3Bile acid-independent bile flowSalt transportersTaurocholate co-transporting polypeptideOrganic solute transporters alphaDependent bile salt transporterApical sodium-dependent bile salt transporterFamilial intrahepatic cholestasis-1Drug-induced cholestasisThe Bile Salt Export Pump: Clinical and Experimental Aspects of Genetic and Acquired Cholestatic Liver Disease
Lam P, Soroka C, Boyer J. The Bile Salt Export Pump: Clinical and Experimental Aspects of Genetic and Acquired Cholestatic Liver Disease. Seminars In Liver Disease 2010, 30: 125-133. PMID: 20422495, PMCID: PMC3008346, DOI: 10.1055/s-0030-1253222.Peer-Reviewed Original ResearchConceptsBenign recurrent intrahepatic cholestasis type 2Progressive familial intrahepatic cholestasis type 2Bile salt export pumpDrug-induced cholestasisType 2Export pumpCholestatic liver diseaseBile salt secretionForms of cholestasisDifferent genetic formsLiver diseaseCholestatic disordersIntrahepatic cholestasisBSEP expressionPathophysiologic processesBSEP deficiencyAnimal modelsCholestasisGenetic formsBile saltsSalt secretionMolecular characteristicsPivotal roleCell culturesPrimary transporter
2001
Cholestatic syndromes
Trauner M, Boyer J. Cholestatic syndromes. Current Opinion In Gastroenterology 2001, 17: 242-256. PMID: 17031165, DOI: 10.1097/00001574-200105000-00007.Peer-Reviewed Original ResearchCholestatic syndromeTotal parenteral nutrition-induced cholestasisParenteral nutrition-induced cholestasisHereditary cholestatic syndromesPrimary biliary cirrhosisCholestasis of pregnancyCholestatic liver diseaseDrug-induced cholestasisHepatobiliary transport proteinsBiliary cirrhosisClinical featuresLiver diseaseBile secretionCholestasisSyndromePathogenesisImportant new studiesNew studiesCholangitisCirrhosisPregnancyDiseaseSecretionTransporter gene
1999
Cholestatic syndromes
Trauner M, Boyer J. Cholestatic syndromes. Current Opinion In Gastroenterology 1999, 15: 217-228. PMID: 17023948, DOI: 10.1097/00001574-199905000-00006.Peer-Reviewed Original ResearchCholestatic syndromeBile duct lossPathogenesis of pruritusCholestatic liver injuryPrimary biliary cirrhosisCholestasis of pregnancyCholestatic liver diseaseDrug-induced cholestasisNew treatment strategiesHepatobiliary transport systemsBiliary cirrhosisLiver injuryClinical featuresLiver diseaseTreatment strategiesDuct lossCholestasisSyndromePathogenesisImportant new studiesNew studiesImportant mechanismCholangitisCirrhosisPruritus
1996
Tauroursodeoxycholic acid activates protein kinase C in isolated rat hepatocytes
Beuers U, Throckmorton D, Anderson, Isales C, Thasler W, Kullak-Ublick G, Sauter G, Koebe H, Paumgartner G, Boyer J. Tauroursodeoxycholic acid activates protein kinase C in isolated rat hepatocytes. Gastroenterology 1996, 110: 1553-1563. PMID: 8613063, DOI: 10.1053/gast.1996.v110.pm8613063.Peer-Reviewed Original ResearchConceptsEffect of TUDCATauroursodeoxycholic acidProtein kinase CHepatocellular Ca2Chronic cholestatic liver diseaseCholestatic liver diseaseAlpha-PKCPKC activityLiver diseaseLiver functionRadioenzymatic techniqueExperimental cholestasisPhorbol ester phorbolActivation of PKCKinase CTaurocholic acidImmunofluorescence techniqueAbstractTextMembrane-associated PKC activitySignificant increaseAIMSStimulation of exocytosisUnknown mechanismParticulate membrane fractionHepatocytes