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 outcomesOutcome 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 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 Research
2019
Bile‐Derived Organoids From Patients With Primary Sclerosing Cholangitis Recapitulate Their Inflammatory Immune Profile
Soroka CJ, Assis DN, Alrabadi LS, Roberts S, Cusack L, Jaffe AB, Boyer JL. Bile‐Derived Organoids From Patients With Primary Sclerosing Cholangitis Recapitulate Their Inflammatory Immune Profile. Hepatology 2019, 70: 871-882. PMID: 30561836, DOI: 10.1002/hep.30470.Peer-Reviewed Original ResearchMeSH KeywordsAdultBileCholangiopancreatography, Endoscopic RetrogradeCholangitis, SclerosingCytokinesFemaleFluorescent Antibody TechniqueGene Expression RegulationGenome-Wide Association StudyHumansImaging, Three-DimensionalMaleMiddle AgedOrganoidsRegistriesSensitivity and SpecificitySignal TransductionStem CellsTissue Culture TechniquesConceptsPSC patientsTumor necrosis factor alphaEpithelial cellular adhesion moleculePrimary sclerosing cholangitisChemokine ligand 20End-stage diseaseEndoscopic retrograde cholangiopancreatographyHuman leukocyte antigenT cell chemoattractantNecrosis factor alphaCellular adhesion moleculesGamma-glutamyl transferaseImmune-related genesSclerosing cholangitisClinical courseImmune profileInterleukin-17AProinflammatory mediatorsRetrograde cholangiopancreatographyLeukocyte antigenAnion exchanger 2Factor alphaInflammatory stimuliEffective treatmentBiliary-like cells
2018
Solute Carrier Organic Anion Transporter Family Member 3A1 Is a Bile Acid Efflux Transporter in Cholestasis
Pan Q, Zhang X, Zhang L, Cheng Y, Zhao N, Li F, Zhou X, Chen S, Li J, Xu S, Huang D, Chen Y, Li L, Wang H, Chen W, Cai SY, Boyer JL, Chai J. Solute Carrier Organic Anion Transporter Family Member 3A1 Is a Bile Acid Efflux Transporter in Cholestasis. Gastroenterology 2018, 155: 1578-1592.e16. PMID: 30063921, PMCID: PMC6221191, DOI: 10.1053/j.gastro.2018.07.031.Peer-Reviewed Original ResearchConceptsBile duct ligationLiver tissueBile acidsHepatic levelsHepatoma cell lineFibroblast growth factor 19Cholestatic liver tissuesEfflux transportersCholic acid dietDevelopment of cholestasisGrowth factor 19Sprague-Dawley ratsShorter survival timeBile acid homeostasisHealthy liver tissueReal-time quantitative polymerase chain reactionNuclear factor κBCell linesQuantitative polymerase chain reactionHuman primary hepatocytesMessenger RNALiver injuryCa dietControl miceC57BL/6J miceCenicriviroc, 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
Primary Sclerosing Cholangitis Is Not Rare Among Blacks in a Multicenter North American Consortium
Goldberg DS, Levy C, Yimam K, Gordon SC, Forman L, Verna E, Yu L, Rahimi R, Schwarz K, Eksteen B, Pratt D, Boyer JL, Assis D, Bowlus C. Primary Sclerosing Cholangitis Is Not Rare Among Blacks in a Multicenter North American Consortium. Clinical Gastroenterology And Hepatology 2017, 16: 591-593. PMID: 29102704, PMCID: PMC5860952, DOI: 10.1016/j.cgh.2017.10.028.Peer-Reviewed Original ResearchBile 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 areasCombination Therapy of All-Trans Retinoic Acid With Ursodeoxycholic Acid in Patients With Primary Sclerosing Cholangitis
Assis DN, Abdelghany O, Cai SY, Gossard AA, Eaton JE, Keach JC, Deng Y, Setchell KD, Ciarleglio M, Lindor KD, Boyer JL. Combination Therapy of All-Trans Retinoic Acid With Ursodeoxycholic Acid in Patients With Primary Sclerosing Cholangitis. Journal Of Clinical Gastroenterology 2017, 51: e11-e16. PMID: 27428727, PMCID: PMC5218875, DOI: 10.1097/mcg.0000000000000591.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overAlanine TransaminaseAlkaline PhosphataseBile Acids and SaltsCholagogues and CholereticsCholangitis, SclerosingCholestenonesDrug Therapy, CombinationFemaleHumansLiverLiver Function TestsMaleMiddle AgedPilot ProjectsTreatment OutcomeTretinoinUrsodeoxycholic AcidYoung AdultConceptsPrimary sclerosing cholangitisUrsodeoxycholic acidAlanine aminotransferaseUDCA monotherapyPrimary endpointSclerosing cholangitisMedian serum alanine aminotransferasePilot studyWeeks of therapyMarkers of inflammationSerum alanine aminotransferaseRetinoic acidAlkaline phosphataseAll-Trans Retinoic AcidSerum ALP levelsHuman pilot studyCombination of ATRAAddition of ATRABile acid synthesisTrans retinoic acidExploratory pilot studyALT levelsAccepted therapyWeek 12C4 levels
2016
Sirtuin 1 activation alleviates cholestatic liver injury in a cholic acid–fed mouse model of cholestasis
Kulkarni SR, Soroka CJ, Hagey LR, Boyer JL. Sirtuin 1 activation alleviates cholestatic liver injury in a cholic acid–fed mouse model of cholestasis. Hepatology 2016, 64: 2151-2164. PMID: 27639250, PMCID: PMC5115990, DOI: 10.1002/hep.28826.Peer-Reviewed Original ResearchConceptsCholestatic liver injuryLiver injurySRT1720 administrationSIRT1 expressionCa dietMouse modelFibroblast growth factor 15Proliferator-activated receptor gamma coactivator 1Multidrug resistance-associated protein 2Peroxisome proliferator-activated receptor gamma coactivator 1Hepatic BA compositionHepatic BA synthesisGrowth factor 15Receptor gamma coactivator 1Resistance-associated protein 2Plasma alanine aminotransferasePlasma BA concentrationsCultured primary human hepatocytesNovel therapeutic targetSirtuin 1 activationFarnesoid X receptorMiR-34a expressionSIRT1 messenger RNACytochrome P450 7A1Bile acid sensorCFTR-associated ligand is a negative regulator of Mrp2 expression
Li M, Soroka CJ, Harry K, Boyer JL. CFTR-associated ligand is a negative regulator of Mrp2 expression. American Journal Of Physiology - Cell Physiology 2016, 312: c40-c46. PMID: 27834195, PMCID: PMC5283898, DOI: 10.1152/ajpcell.00100.2016.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsCarrier ProteinsCells, CulturedChlorocebus aethiopsCOS CellsDown-RegulationGene Expression RegulationGolgi Matrix ProteinsHepatocytesHumansMaleMembrane ProteinsMembrane Transport ProteinsMiceMultidrug Resistance-Associated Protein 2Multidrug Resistance-Associated ProteinsRatsRats, Sprague-DawleySignal TransductionConceptsPull-down assaysGST pull-down assaysCOOH-terminal PDZNegative regulatorCotransfected COS-7 cellsGlutathione S-transferase fusion proteinS-transferase fusion proteinATP-binding cassette (ABC) transportersTrans-Golgi networkCystic fibrosis transmembrane conductance regulatorProtein-protein interactionsExchanger regulatory factor 1Fibrosis transmembrane conductance regulatorStreptavidin pull-down assaysTransmembrane conductance regulatorCOS-7 cellsRegulatory factor 1PDZ domainCell surface expressionPosttranscriptional regulationTransmembrane proteinPlasma membraneLLC-PK1 cellsCassette transportersCOS-7
2015
Na+/H+ exchanger regulatory factor 1 knockout mice have an attenuated hepatic inflammatory response and are protected from cholestatic liver injury
Li M, Mennone A, Soroka CJ, Hagey LR, Ouyang X, Weinman EJ, Boyer JL. Na+/H+ exchanger regulatory factor 1 knockout mice have an attenuated hepatic inflammatory response and are protected from cholestatic liver injury. Hepatology 2015, 62: 1227-1236. PMID: 26108984, PMCID: PMC4589453, DOI: 10.1002/hep.27956.Peer-Reviewed Original ResearchConceptsBile duct ligationLiver injuryInflammatory responseICAM-1BDL miceBDL-induced liver injuryNeutrophil-mediated liver injuryTotal bile acid concentrationTumor necrosis factor alphaIntercellular adhesion molecule-1Hepatic neutrophil accumulationAttenuated liver injuryCholestatic liver injuryHepatic inflammatory responseMouse liverSerum alanine aminotransferaseBile acid concentrationsHepatic inflammatory diseasesICAM-1 expressionNecrosis factor alphaAdhesion molecule-1Wild-type miceICAM-1 proteinNew therapeutic targetsMessenger RNA levelsFibrates 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 failureCanalicular membrane MRP2/ABCC2 internalization is determined by Ezrin Thr567 phosphorylation in human obstructive cholestasis
Chai J, Cai SY, Liu X, Lian W, Chen S, Zhang L, Feng X, Cheng Y, He X, He Y, Chen L, Wang R, Wang H, Boyer JL, Chen W. Canalicular membrane MRP2/ABCC2 internalization is determined by Ezrin Thr567 phosphorylation in human obstructive cholestasis. Journal Of Hepatology 2015, 63: 1440-1448. PMID: 26212029, PMCID: PMC4686151, DOI: 10.1016/j.jhep.2015.07.016.Peer-Reviewed Original ResearchMeSH KeywordsAdultBile CanaliculiCase-Control StudiesCholestasisCytoskeletal ProteinsFemaleGallstonesGene Knockdown TechniquesHep G2 CellsHumansLiverMaleMembrane ProteinsMiddle AgedModels, BiologicalMultidrug Resistance-Associated Protein 2Multidrug Resistance-Associated ProteinsPhosphorylationProtein Kinase CReceptors, Autocrine Motility FactorRNA, MessengerThreonineConceptsObstructive cholestasisCholestatic liverMRP2 expressionMrp2 internalizationHepG2 cellsHuman obstructive cholestasisMRP2 protein expressionMembrane expressionHepatic MRP2 expressionNon-cholestatic controlsExpression of PKCαTotal protein levelsBile ductCholestatic patientsCholestasisBile acidsPatientsAbstractTextHuman liverProtein expressionProtein levelsLiverMRP2JaundiceAIMS
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 polymorphismsAdult sea lamprey tolerates biliary atresia by altering bile salt composition and renal excretion
Cai S, Lionarons DA, Hagey L, Soroka CJ, Mennone A, Boyer JL. Adult sea lamprey tolerates biliary atresia by altering bile salt composition and renal excretion. Hepatology 2013, 57: 2418-2426. PMID: 23175353, PMCID: PMC3604052, DOI: 10.1002/hep.26161.Peer-Reviewed Original ResearchConceptsRenal excretionBile salt compositionBiliary atresiaBile saltsPlasma bile salt levelsEvidence of necrosisAdult liverBile salt levelsBile salt homeostasisNormal plasma levelsForms of cholestasisBile salt transportersCollection of urineAdult lampreysPredominant bile saltProgressive diseaseExogenous organic anionsBile ductPlasma levelsMajor bile saltsAnimal modelsC27 bile alcoholsCholestasisSalt transportersBile alcohols
2011
Ostα depletion protects liver from oral bile acid load
Soroka CJ, Velazquez H, Mennone A, Ballatori N, Boyer JL. Ostα depletion protects liver from oral bile acid load. AJP Gastrointestinal And Liver Physiology 2011, 301: g574-g579. PMID: 21719738, PMCID: PMC3174539, DOI: 10.1152/ajpgi.00141.2011.Peer-Reviewed Original ResearchConceptsExcess bile acidsCholic acid feedingWild-type miceBile acid overloadBile acidsLiver injuryAcid overloadLower serum ALT levelsIntestinal bile acid absorptionAcid feedingBile acid loadSerum ALT levelsBile acid absorptionBile acid lossBile duct ligationEffective therapeutic targetBile acid homeostasisWild-type controlsALT levelsUrinary eliminationIntestinal lossObstructive cholestasisIntestinal functionDuct ligationUrinary clearance
2010
Combination of retinoic acid and ursodeoxycholic acid attenuates liver injury in bile duct–ligated rats and human hepatic cells
He H, Mennone A, Boyer JL, Cai S. Combination of retinoic acid and ursodeoxycholic acid attenuates liver injury in bile duct–ligated rats and human hepatic cells. Hepatology 2010, 53: 548-557. PMID: 21274875, PMCID: PMC3069505, DOI: 10.1002/hep.24047.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBile Acids and SaltsBile DuctsCell ProliferationCells, CulturedCholestasis, IntrahepaticCholesterol 7-alpha-HydroxylaseCollagen Type ICollagen Type I, alpha 1 ChainDisease Models, AnimalHepatocytesHumansLigationLiverMaleMatrix Metalloproteinase 2RatsRats, Sprague-DawleySmad2 ProteinTretinoinUrsodeoxycholic AcidConceptsBile duct ligationBile salt pool sizeLX-2 cellsUrsodeoxycholic acidHepatic stellate cellsRetinoic acidLiver fibrosisStellate cellsPhosphate-buffered salineCommon bile duct ligationMale Sprague-Dawley ratsPrimary human hepatic stellate cellsTumor necrosis factor αBile duct-ligated ratsHuman hepatic stellate cellsBile duct proliferationHuman hepatocytesLiver hydroxyproline contentNecrosis factor αSprague-Dawley ratsAcute promyelocytic leukemiaΑ-SMA expressionDuct-ligated ratsSmooth muscle actinMatrix metalloproteinase-2
2006
The organic anion transport polypeptide 1d1 (Oatp1d1) mediates hepatocellular uptake of phalloidin and microcystin into skate liver
Meier-Abt F, Hammann-Hänni A, Stieger B, Ballatori N, Boyer J. The organic anion transport polypeptide 1d1 (Oatp1d1) mediates hepatocellular uptake of phalloidin and microcystin into skate liver. Toxicology And Applied Pharmacology 2006, 218: 274-279. PMID: 17198718, DOI: 10.1016/j.taap.2006.11.015.Peer-Reviewed Original ResearchConceptsSkate liverToxic liver injuryFunctional transport activityLiver-specific OATPsOrganic anion transporting polypeptidesLiver injuryOrganic anion transportersWater-injected oocytesXenobiotic toxinsHepatocellular uptakeBile saltsSkate hepatocytesOATP substratesHuman brainLiverPresent studyOatps/OATPsAnion transportersOATPDemethylphalloinHepatocytesTransport activityToxinCellular uptakeUptake