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
2022
Fenofibrate Downregulates NF-κB Signaling to Inhibit Pro-inflammatory Cytokine Secretion in Human THP-1 Macrophages and During Primary Biliary Cholangitis
Gallucci GM, Alsuwayt B, Auclair AM, Boyer JL, Assis DN, Ghonem NS. Fenofibrate Downregulates NF-κB Signaling to Inhibit Pro-inflammatory Cytokine Secretion in Human THP-1 Macrophages and During Primary Biliary Cholangitis. Inflammation 2022, 45: 2570-2581. PMID: 35838934, PMCID: PMC10853883, DOI: 10.1007/s10753-022-01713-1.Peer-Reviewed Original ResearchConceptsPrimary biliary cholangitisPrimary sclerosing cholangitisAnti-inflammatory mechanismsChronic liver diseaseNF-κB signalingBiliary cholangitisLiver diseaseNF-κB p50IL-1βIL-8Peroxisome proliferator-activated receptor alphaPro-inflammatory cytokine secretionProliferator-activated receptor alphaIncomplete biochemical responseAnti-inflammatory effectsAddition of fenofibratePro-inflammatory cytokinesPPARα-dependent mannerHuman THP-1 macrophagesP65 protein expressionLabel therapeutic optionTHP-1 macrophagesTHP-1 cellsSclerosing cholangitisAdult patientsPrimary biliary cholangitis: 2021 practice guidance update from the American Association for the Study of Liver Diseases
Lindor KD, Bowlus CL, Boyer J, Levy C, Mayo M. Primary biliary cholangitis: 2021 practice guidance update from the American Association for the Study of Liver Diseases. Hepatology 2022, 75: 1012-1013. PMID: 34431119, DOI: 10.1002/hep.32117.Peer-Reviewed Original Research
2021
Outcome of COVID‐19 in Patients With Autoimmune Hepatitis: An International Multicenter Study
Efe C, Dhanasekaran R, Lammert C, Ebik B, la Tijera F, Aloman C, Calışkan A, Peralta M, Gerussi A, Massoumi H, Catana AM, Torgutalp M, Purnak T, Rigamonti C, Aldana A, Khakoo N, Kacmaz H, Nazal L, Frager S, Demir N, Irak K, Ellik ZM, Balaban Y, Atay K, Eren F, Cristoferi L, Batıbay E, Urzua Á, Snijders R, Kıyıcı M, Akyıldız M, Ekin N, Carr RM, Harputluoğlu M, Hatemi I, Mendizabal M, Silva M, Idilman R, Silveira M, Drenth JPH, Assis DN, Björnsson E, Boyer JL, Invernizzi P, Levy C, Schiano TD, Ridruejo E, Wahlin S. Outcome of COVID‐19 in Patients With Autoimmune Hepatitis: An International Multicenter Study. Hepatology 2021, 73: 2099-2109. PMID: 33713486, PMCID: PMC8250536, DOI: 10.1002/hep.31797.Peer-Reviewed Original ResearchConceptsSevere COVID-19Chronic liver diseaseAutoimmune hepatitisLiver injuryMulticenter studyCOVID-19Causes of CLDPropensity score-matched cohortSevere COVID-19 outcomesContinuation of immunosuppressionMaintenance of immunosuppressionOutcomes of patientsIntensive care admissionUse of antiviralsInternational multicenter studyCOVID-19 outcomesCOVID-19 diagnosisContinued immunosuppressionCare admissionCause mortalityIndependent predictorsMedian ageLiver diseaseMechanical ventilationRetrospective study
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 diseaseThe Role of Bile Acid‐Mediated Inflammation in Cholestatic Liver Injury
Cai S, Li M, Boyer J. The Role of Bile Acid‐Mediated Inflammation in Cholestatic Liver Injury. 2020, 728-736. DOI: 10.1002/9781119436812.ch56.Peer-Reviewed Original ResearchCholestatic liver injuryBile acidsLiver injuryProinflammatory mediatorsInflammatory responseCauses of cholestasisAlcoholic liver diseasePrimary biliary cholangitisConjugated bile acidsEffects of drugsHepatic infiltrationBile acid transporterLiver transplantationViral hepatitisBiliary cholangitisBiliary cirrhosisMetabolic syndromeDuct obstructionLiver diseaseImmune cellsNeutrophil activationPathophysiological levelsCholangitisInflammationInjuryPrimary Biliary Cholangitis: 2018 Practice Guidance From the American Association for the Study of Liver Diseases
Lindor K, Bowlus C, Boyer J, Levy C, Mayo M. Primary Biliary Cholangitis: 2018 Practice Guidance From the American Association for the Study of Liver Diseases. Clinical Liver Disease 2020, 15: 1-2. PMCID: PMC7041951, DOI: 10.1002/cld.874.Peer-Reviewed Original Research
2019
Primary Biliary Cholangitis: 2018 Practice Guidance from the American Association for the Study of Liver Diseases
Lindor KD, Bowlus CL, Boyer J, Levy C, Mayo M. Primary Biliary Cholangitis: 2018 Practice Guidance from the American Association for the Study of Liver Diseases. Hepatology 2019, 69: 394-419. PMID: 30070375, DOI: 10.1002/hep.30145.Peer-Reviewed Original Research
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 areasFRI-393 Macrophage migration inhibitory factor (MIF) modulates T-cell proliferation and hepatic inflammation in a model of autoimmune liver disease
Roberts S, Leng L, Soroka C, Boyer J, Bucala R, Assis D. FRI-393 Macrophage migration inhibitory factor (MIF) modulates T-cell proliferation and hepatic inflammation in a model of autoimmune liver disease. Journal Of Hepatology 2017, 66: s363-s364. DOI: 10.1016/s0168-8278(17)31067-x.Peer-Reviewed Original Research
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
2013
The role of macrophage migration inhibitory factor in autoimmune liver disease
Assis DN, Leng L, Du X, Zhang CK, Grieb G, Merk M, Garcia AB, McCrann C, Chapiro J, Meinhardt A, Mizue Y, Nikolic‐Paterson D, Bernhagen J, Kaplan MM, Zhao H, Boyer JL, Bucala R. The role of macrophage migration inhibitory factor in autoimmune liver disease. Hepatology 2013, 59: 580-591. PMID: 23913513, PMCID: PMC3877200, DOI: 10.1002/hep.26664.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntigens, Differentiation, B-LymphocyteBiomarkersBiopsyCase-Control StudiesCohort StudiesFemaleGene FrequencyHepatitis, AutoimmuneHistocompatibility Antigens Class IIHumansIntramolecular OxidoreductasesLiverLiver Cirrhosis, BiliaryMacrophage Migration-Inhibitory FactorsMaleMicrosatellite RepeatsMiddle AgedPhenotypePolymorphism, Single NucleotideConceptsMacrophage migration inhibitory factorPrimary biliary cirrhosisAutoimmune hepatitisMigration inhibitory factorMIF receptorHealthy controlsInhibitory factorAutoimmune liver diseaseMIF promoter polymorphismsHepatic stellate cellsEnzyme-linked immunosorbentCATT7 alleleImmunopathogenic basisMIF expressionMIF locusBiliary cirrhosisLiver diseaseInflammatory phenotypeReceptor profileStellate cellsPromoter polymorphismPatientsSerum samplesCD74Single nucleotide polymorphisms
2010
The 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 transporterCholestasis: 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 cholestasis
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
1995
A randomized, double-blind, placebo-controlled trial of ursodeoxycholic acid in primary biliary cirrhosis
Combes B, Carithers R, Maddrey W, Lin D, Mcdonald M, Wheeler D, Eigenbrodt E, Muñoz S, Rubin R, Garcia-tsao G, Bonner G, West A, Boyer J, Luketic V, Shiffman M, Mills A, Peters M, White H, Zetterman R, Rossi S, Hofmann A, Markin R. A randomized, double-blind, placebo-controlled trial of ursodeoxycholic acid in primary biliary cirrhosis. Hepatology 1995, 22: 759-766. DOI: 10.1016/0270-9139(95)90294-5.Peer-Reviewed Original ResearchPrimary biliary cirrhosisSerum bilirubinBiliary cirrhosisMajor complicationsStratum 1Liver diseaseTreatment failureAdvanced primary biliary cirrhosisPlacebo-treated patientsPlacebo-controlled trialBile acid poolStratum 3Advanced diseaseLiver histologyPrognostic factorsMilder diseaseSingle doseUrsodeoxycholic acidUrsodiolSevere symptomsPatientsPlaceboLaboratory testsComplicationsBilirubin