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
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 inhibitorFenofibrate 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
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
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 ResearchCombination 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
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 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 alcoholsBiosynthesis and trafficking of the bile salt export pump, BSEP: Therapeutic implications of BSEP mutations
Soroka CJ, Boyer JL. Biosynthesis and trafficking of the bile salt export pump, BSEP: Therapeutic implications of BSEP mutations. Molecular Aspects Of Medicine 2013, 37: 3-14. PMID: 23685087, PMCID: PMC3784619, DOI: 10.1016/j.mam.2013.05.001.Peer-Reviewed Original ResearchConceptsBenign recurrent intrahepatic cholestasis type 2Progressive familial intrahepatic cholestasis type 2Cell biological aspectsBile salt export pumpTranslational regulationCell biologyMembrane transportersPrimary transporterBile salt-dependent bile flowType 2Bile acidsRate-limiting stepExport pumpDrug-induced cholestasisBiological aspectsBiosynthesisTraffickingTransportersBSEP mutationsMutationsCholestatic diseaseIntrahepatic cholestasisBile flowBiliary systemEnterohepatic circulation
2007
Clinical trial: modulation of human placental multidrug resistance proteins in cholestasis of pregnancy by ursodeoxycholic acid
AZZAROLI F, MENNONE A, FELETTI V, SIMONI P, BAGLIVO E, MONTAGNANI M, RIZZO N, PELUSI G, DE ALOYSIO D, LODATO F, FESTI D, COLECCHIA A, RODA E, BOYER J, MAZZELLA G. Clinical trial: modulation of human placental multidrug resistance proteins in cholestasis of pregnancy by ursodeoxycholic acid. Alimentary Pharmacology & Therapeutics 2007, 26: 1139-1146. PMID: 17894656, DOI: 10.1111/j.1365-2036.2007.03462.x.Peer-Reviewed Original ResearchConceptsUrsodeoxycholic acid administrationBile acid levelsUrsodeoxycholic acidBile acidsAcid administrationIntrahepatic cholestasisCord bloodMaternal serum bile acidsCord blood bilirubinAcid levelsRNA expressionCholestasis of pregnancySerum bile acidsTotal bile acidsMRP3 protein expressionPregnancy patientsPhysiological pregnancyPregnant womenMultidrug resistance proteinBlood bilirubinMRP2 expressionMRP4 expressionCholestasisMultidrug resistancePregnancy
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
1999
Hepatic Toxicity and Persistence of ser/thr Protein Phosphatase Inhibition by Microcystin in the Little Skate Raja erinacea
Runnegar M, Seward D, Ballatori N, Crawford J, Boyer J. Hepatic Toxicity and Persistence of ser/thr Protein Phosphatase Inhibition by Microcystin in the Little Skate Raja erinacea. Toxicology And Applied Pharmacology 1999, 161: 40-49. PMID: 10558922, DOI: 10.1006/taap.1999.8783.Peer-Reviewed Original ResearchConceptsDose-dependent inhibitionSkate hepatocytesUptake of microcystinNear complete inhibitionPP activityInflammatory changesHepatic toxicityHepatocyte necrosisHistological changesAccompanying inhibitionHepatic lesionsBile acidsHigh dosesOnly organSignificant inhibitionSkate Raja erinaceaLittle skate Raja erinaceaInhibitionLiverRectal glandBiliary bile acids in primary biliary cirrhosis: Effect of ursodeoxycholic acid
Combes B, Carithers R, Maddrey W, Munoz S, Garcia‐Tsao G, Bonner G, Boyer J, Luketic V, Shiffman M, Peters M, White H, Zetterman R, Risser R, Rossi S, Hofmann A. Biliary bile acids in primary biliary cirrhosis: Effect of ursodeoxycholic acid. Hepatology 1999, 29: 1649-1654. PMID: 10347103, PMCID: PMC4004074, DOI: 10.1002/hep.510290618.Peer-Reviewed Original ResearchMeSH KeywordsBileBile Acids and SaltsChenodeoxycholic AcidCholic AcidChromatography, GasChromatography, High Pressure LiquidDeoxycholic AcidDouble-Blind MethodDrug Administration ScheduleFemaleHumansLithocholic AcidLiver Cirrhosis, BiliaryMaleMiddle AgedPlacebosRegression AnalysisReproducibility of ResultsTime FactorsUrsodeoxycholic AcidConceptsPrimary biliary cirrhosisBile acid compositionUrsodeoxycholic acidBile acidsBiliary cirrhosisSeverity of PBCSingle bedtime dosePlacebo-controlled trialBiliary bile acidsEndogenous bile acidsMajor bile acidsBedtime dosePlacebo medicationDuodenal bileHigh-pressure liquid chromatography methodPatientsNormal personsBileSignificant decreaseCirrhosisAcid compositionCDCATaurineLiquid chromatography methodYears
1998
Maternal cholestasis does not affect the ontogenic pattern of expression of the Na+/Taurocholate cotransporting polypeptide (ntcp) in the fetal and neonatal rat liver
Arrese M, Trauner M, Ananthanarayanan M, Boyer J, Suchy F. Maternal cholestasis does not affect the ontogenic pattern of expression of the Na+/Taurocholate cotransporting polypeptide (ntcp) in the fetal and neonatal rat liver. Hepatology 1998, 28: 789-795. PMID: 9731574, DOI: 10.1002/hep.510280328.Peer-Reviewed Original ResearchConceptsBile duct ligationWeeks of ageBile acid transporterFetal lifeCommon bile duct ligationOntogenic patternMaternal obstructive cholestasisBile acid excretionMRNA levelsEffect of cholestasisSham-operated animalsSteady-state mRNA levelsFunction of NTCPAcid transportersNeonatal rat liverPostnatal time pointsDays of ageMaternal cholestasisBasolateral bile acid transportersPregnant ratsCholestatic ratsLiver weightObstructive cholestasisDuct ligationMC group
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. PMID: 7657280, DOI: 10.1002/hep.1840220311.Peer-Reviewed Original ResearchConceptsPrimary biliary cirrhosisSerum bilirubinBiliary cirrhosisStratum 1Advanced primary biliary cirrhosisPlacebo-controlled trialBile acid poolLiver histologyPrognostic factorsTreatment failureSingle doseUrsodeoxycholic acidSevere symptomsPatientsUrsodiolLaboratory testsPlaceboHistologyBilirubinCirrhosisBiochemical testsGood responseStratum 3Acid poolLess effectHyperammonemic coma due to parenteral nutrition in a woman with heterozygous ornithine transcarbamylase deficiency
Felig D, Brusilow S, Boyer J. Hyperammonemic coma due to parenteral nutrition in a woman with heterozygous ornithine transcarbamylase deficiency. Gastroenterology 1995, 109: 282-284. PMID: 7797025, DOI: 10.1016/0016-5085(95)90295-3.Peer-Reviewed Original ResearchConceptsOrnithine transcarbamylase deficiencyParenteral nutritionNormal liver function test resultsLiver function test resultsLow plasma citrullineTotal parenteral nutritionFunction test resultsTolerance test resultsPartial enzyme deficiencyPartial ornithine transcarbamylase deficiencyUlcerative colitisParenteral alimentationHyperammonemic encephalopathyCase reportPlasma citrullineHyperammonemic comaPlasma glutamineAdult womenUnique caseSimilar episodesElevated levelsEnzyme deficiencySymptomatic expressionHemizygous malesWomenExpression of sodium-independent organic anion uptake systems of skate liver in Xenopus laevis oocytes
Jacquemin E, Hagenbuch B, Wolkoff A, Meier P, Boyer J. Expression of sodium-independent organic anion uptake systems of skate liver in Xenopus laevis oocytes. American Journal Of Physiology 1995, 268: g18-g23. PMID: 7840202, DOI: 10.1152/ajpgi.1995.268.1.g18.Peer-Reviewed Original ResearchConceptsBSP uptakeSkate liverTaurocholate uptakeXenopus laevis oocytesOrganic anion transport systemInjection of oocytesLaevis oocytesLiverAnion transport systemRat liverSulfobromophthalein uptakeUptake systemOocytesMRNADisulfonic acidUptake activityFunctional expressionLiver mRNAUptakeExpressionSerum albuminLower vertebrates