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 junctionsBile Acid Induced Inflammation and the Role of β-Catenin
Boyer J. Bile Acid Induced Inflammation and the Role of β-Catenin. Cellular And Molecular Gastroenterology And Hepatology 2023, 16: 1033. PMID: 37690462, PMCID: PMC10685134, DOI: 10.1016/j.jcmgh.2023.08.009.Commentaries, Editorials and LettersOrganic Anion Transporting Polypeptide (OATP) 1B3 is a Significant Transporter for Hepatic Uptake of Conjugated Bile Acids in Humans
Pan Q, Zhu G, Xu Z, Zhu J, Ouyang J, Tong Y, Zhao N, Zhang X, Cheng Y, Zhang L, Tan Y, Li J, Zhang C, Chen W, Cai S, Boyer J, Chai J. Organic Anion Transporting Polypeptide (OATP) 1B3 is a Significant Transporter for Hepatic Uptake of Conjugated Bile Acids in Humans. Cellular And Molecular Gastroenterology And Hepatology 2023, 16: 223-242. PMID: 37146714, PMCID: PMC10394288, DOI: 10.1016/j.jcmgh.2023.04.007.Peer-Reviewed Original ResearchConceptsBA uptake transportersBile duct ligationHepatic neutrophil infiltrationCholestatic liver injuryProinflammatory cytokine productionCholic acid dietAdaptive protective responseLiver-specific overexpressionWild-type miceConjugated bile acidsUptake transportersPrimary hepatocytesUDCA feedingNeutrophil infiltrationBDL miceLiver injuryCytokine productionBile flowDuct ligationOrganic anion transporting polypeptide (OATP) 1B3Conjugated BAsTransgenic miceHepatic uptakeBile acidsProtective responseUnique DUOX2(+)ACE2(+) small cholangiocytes are pathogenic targets for primary biliary cholangitis.
Li X, Li Y, Xiao J, Wang H, Guo Y, Mao X, Shi P, Hou Y, Zhang X, Zhao N, Zheng M, He Y, Ding J, Tan Y, Liao M, Li L, Peng Y, Li X, Pan Q, Xie Q, Li Q, Li J, Li Y, Chen Z, Huang Y, Assis DN, Cai SY, Boyer JL, Huang X, Tang CE, Liu X, Peng S, Chai J. Unique DUOX2(+)ACE2(+) small cholangiocytes are pathogenic targets for primary biliary cholangitis. Nat Commun 2023, 14: 29. PMID: 36759512, DOI: 10.1038/s41467-022-34606-w.Peer-Reviewed Original ResearchRunt-related transcription factor-1 ameliorates bile acid–induced hepatic inflammation in cholestasis through JAK/STAT3 signaling
Zhang L, Pan Q, Zhang L, Xia H, Liao J, Zhang X, Zhao N, Xie Q, Liao M, Tan Y, Li Q, Zhu J, Li L, Fan S, Li J, Zhang C, Cai S, Boyer J, Chai J. Runt-related transcription factor-1 ameliorates bile acid–induced hepatic inflammation in cholestasis through JAK/STAT3 signaling. Hepatology 2023, 77: 1866-1881. PMID: 36647589, PMCID: PMC10921919, DOI: 10.1097/hep.0000000000000041.Peer-Reviewed Original ResearchConceptsJAK/STAT3Bile duct ligationInflammatory responseLiver injuryCholestatic patientsTranscription factor 1Duct ligationBile acidsLiver inflammatory responseCholestatic liver injuryHepatic inflammatory responseElevated bile acidsCholic acid dietFactor 1Cholic acid feedingLiver-specific ablationNew therapeutic targetsLiver-specific deletionCholestatic miceHepatic inflammationLiver inflammationInflammatory chemokinesHepatic expressionMouse modelAcid diet
2021
Adjunct Fenofibrate Up‐regulates Bile Acid Glucuronidation and Improves Treatment Response For Patients With Cholestasis
Gallucci GM, Trottier J, Hemme C, Assis DN, Boyer JL, Barbier O, Ghonem NS. Adjunct Fenofibrate Up‐regulates Bile Acid Glucuronidation and Improves Treatment Response For Patients With Cholestasis. Hepatology Communications 2021, 5: 2035-2051. PMID: 34558841, PMCID: PMC8631103, DOI: 10.1002/hep4.1787.Peer-Reviewed Original ResearchConceptsSerum bile acidsSerum alkaline phosphataseBile acidsTreatment responseIncomplete responseTotal serum bile acidsElevated serum alkaline phosphatasePeroxisome proliferator-activated receptor alphaProliferator-activated receptor alphaAlkaline phosphatasePrimary sclerosing cholangitisPrimary biliary cholangitisStandard of careSerum ALP levelsBile acid glucuronidationCytotoxic bile acidsPrimary human hepatocytesBA detoxificationFenofibrate therapySclerosing cholangitisAdult patientsBiliary cholangitisLiver failureCombination therapyImproved outcomesIn Memoriam: Peter J. Meier (1947–2021)
Stieger B, Boyer JL. In Memoriam: Peter J. Meier (1947–2021). Journal Of Hepatology 2021, 75: 761-762. DOI: 10.1016/j.jhep.2021.06.039.Peer-Reviewed Original ResearchOutcome 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 studyRole of Biliary Organoids in Cholestasis Research and Regenerative Medicine
Soroka CJ, Roberts SJ, Boyer JL, Assis DN. Role of Biliary Organoids in Cholestasis Research and Regenerative Medicine. Seminars In Liver Disease 2021, 41: 206-212. PMID: 33957696, DOI: 10.1055/s-0041-1728663.Peer-Reviewed Original ResearchConceptsHuman cholestatic diseasesCholestatic diseaseBiliary organoidsStudy of pathophysiologyCholestasis ResearchBiliary treeDisease stageIndividual patientsTranslational studiesPrimary cholangiocytesPersonalized approachBiliary tissueApplication of organoidsStandardization of terminologyTranslational medicineDiseaseOrganoidsMedicineOrganoid technologyPatientsPathophysiologyThe role of bile acids in cholestatic liver injury
Cai SY, Boyer JL. The role of bile acids in cholestatic liver injury. Annals Of Translational Medicine 2021, 9: 737-737. PMID: 33987435, PMCID: PMC8106037, DOI: 10.21037/atm-20-5110.Peer-Reviewed Original ResearchCholestatic liver injuryBile duct proliferationLiver injuryParenchymal cell deathBile acidsDuct proliferationImmune cellsStellate cellsProliferation of cholangiocytesSphingosine-1-phosphate receptor 2Bile acid receptorCell deathMajor cellular componentLiver inflammationClinical evidenceInflammatory cytokinesLiver fibrosisPathogenic rolePathologic effectsReceptor 2Mitochondrial injuryAcid receptorsClinical disordersInjuryOxidative stressBile formation and secretion: An update
Boyer JL, Soroka CJ. Bile formation and secretion: An update. Journal Of Hepatology 2021, 75: 190-201. PMID: 33617926, DOI: 10.1016/j.jhep.2021.02.011.Peer-Reviewed Original ResearchThe role of the retinoid receptor, RAR/RXR heterodimer, in liver physiology
Li B, Cai SY, Boyer JL. The role of the retinoid receptor, RAR/RXR heterodimer, in liver physiology. Biochimica Et Biophysica Acta (BBA) - Molecular Basis Of Disease 2021, 1867: 166085. PMID: 33497820, PMCID: PMC11152086, DOI: 10.1016/j.bbadis.2021.166085.Peer-Reviewed Original ResearchConceptsRAR/retinoid X receptorRetinoid X receptorRAR/RXR heterodimersRetinoic acid receptorsRXR heterodimersLiver physiologySpecific genesMetabolism of lipidsBiological processesDetailed signalingLiver genesEmbryo developmentFunctional roleHepatic stellate cellsCell proliferationRetinoid receptorsX receptorGenesMechanistic viewHeterodimersPhysiologyCholesterol transportAcid receptorsStellate cellsVitamin A
2020
Hepatic NFAT signaling regulates the expression of inflammatory cytokines in cholestasis
Cai SY, Yu D, Soroka CJ, Wang J, Boyer JL. Hepatic NFAT signaling regulates the expression of inflammatory cytokines in cholestasis. Journal Of Hepatology 2020, 74: 550-559. PMID: 33039404, PMCID: PMC7897288, DOI: 10.1016/j.jhep.2020.09.035.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsATP Binding Cassette Transporter, Subfamily BBile Acids and SaltsCells, CulturedCholangitis, SclerosingCytokinesDisease Models, AnimalFemaleGene Expression RegulationGene Knockdown TechniquesHepatocytesHumansLiverLiver Cirrhosis, BiliaryMiceMice, Inbred C57BLMice, KnockoutNFATC Transcription FactorsPyrazolesSignal TransductionTreatment OutcomeConceptsCholestatic liver injuryLiver injuryInflammatory genesIL-8NFAT activationCholestatic liver tissuesHepatic cytokine expressionReduced liver injurySpecific NFAT inhibitorsHepatic inflammatory responseInduces liver injuryMouse hepatocytesIL-8 expressionActivated T cellsIL-8 promoterElevated tissue levelsGene reporterInflammatory cytokinesCytokine expressionElevated mRNA levelsInflammatory responseCholestatic liverT cellsImmune responseNFAT inhibitorAS055 Co-culture of bile-derived organoids from primary sclerosing cholangitis patients with CD4+ T cells replicates pathogenic, CCL20 dependent biliary-immune interactions
Soroka C, Roberts S, Hohenester S, Boyer J, Assis D. AS055 Co-culture of bile-derived organoids from primary sclerosing cholangitis patients with CD4+ T cells replicates pathogenic, CCL20 dependent biliary-immune interactions. Journal Of Hepatology 2020, 73: s41. DOI: 10.1016/s0168-8278(20)30634-6.Peer-Reviewed Original ResearchFenofibrate 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 diseaseOrganic Solute Transporter Alpha Deficiency: A Disorder With Cholestasis, Liver Fibrosis, and Congenital Diarrhea
Gao E, Cheema H, Waheed N, Mushtaq I, Erden N, Nelson‐Williams C, Jain D, Soroka CJ, Boyer JL, Khalil Y, Clayton PT, Mistry PK, Lifton RP, Vilarinho S. Organic Solute Transporter Alpha Deficiency: A Disorder With Cholestasis, Liver Fibrosis, and Congenital Diarrhea. Hepatology 2020, 71: 1879-1882. PMID: 31863603, PMCID: PMC8577800, DOI: 10.1002/hep.31087.Peer-Reviewed Original ResearchHormonal Regulation of Cholangiocyte Secretion
Gigliozzi A, Fraioli F, Boyer J. Hormonal Regulation of Cholangiocyte Secretion. 2020, 89-95. DOI: 10.1201/9780367813888-8.Peer-Reviewed Original ResearchVasoactive intestinal peptideCholangiocyte secretionBicarbonate secretionBicarbonate-rich choleresisPost-prandial phaseExert inhibitory effectsCGMP-independent pathwayBicarbonate excretionIntestinal peptideParasympathetic systemPKA-dependent pathwayHepatic bileCholangiocyte proliferationActivation of calcineurinMaximal stimulationInhibitory effectSecretionBicarbonate requirementEnhanced expressionAdenylyl cyclaseHormonal regulationDigestive functionMajor determinantActivationCorticosteroidsThe 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 levelsCholangitisInflammationInjuryAdaptive Regulation of Hepatocyte Transporters in Cholestasis
Boyer J. Adaptive Regulation of Hepatocyte Transporters in Cholestasis. 2020, 378-389. DOI: 10.1002/9781119436812.ch31.Peer-Reviewed Original ResearchSignal transduction pathwaysAdaptive responseOrganic solute transporterSecretory polarityTranscription factorsTransduction pathwaysMolecular adaptationsSolute transportersCytoskeleton structureIntracellular vesiclesTarget genesMembrane transportersCellular eventsJunctional proteinsNuclear receptorsCanalicular domainCholestatic phenotypeTransportersTight junctionsVital functionsRegulationAdaptive regulationImportant ligandsEnzymatic reactionsBile salt synthesis