2023
Unique 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 D, Cai S, Boyer J, Huang X, Tang C, Liu X, Peng S, Chai J. Unique DUOX2+ACE2+ small cholangiocytes are pathogenic targets for primary biliary cholangitis. Nature Communications 2023, 14: 29. PMID: 36759512, PMCID: PMC9911648, DOI: 10.1038/s41467-022-34606-w.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme 2AnimalsDual OxidasesEpithelial CellsHumansLiver Cirrhosis, BiliaryMiceConceptsPrimary biliary cholangitisPrimary biliary cholangitis patientsBiliary cholangitisEtiology of primary biliary cholangitisScRNA-seqPathogenic targetsSeverity of diseaseSingle-cell RNA sequencingAMA-M2PBC patientsAutoantibody levelsPolymeric immunoglobulin receptorMemory BMultiplex immunofluorescenceCholangiocyte injuryPlasma cellsAutoimmune diseasesRNAscope analysisCholangiocytesImmunoglobulin receptorBile formationPatientsTherapeutic interventionsMultiplexed IFRNA sequencing
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
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 outcomes
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
2018
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 2018, 69: 394-419. PMID: 30070375, DOI: 10.1002/hep.30145.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
1999
The effect of ursodeoxycholic acid on the florid duct lesion of primary biliary cirrhosis
Combes B, Markin R, Wheeler D, Rubin R, West A, Mills A, Eigenbrodt E, Maddrey W, Munoz S, Garcia‐Tsao G, Bonner G, Boyer J, Luketic V, Shiffman M, Peters M, White H, Zetterman R, Carithers R. The effect of ursodeoxycholic acid on the florid duct lesion of primary biliary cirrhosis. Hepatology 1999, 30: 602-605. PMID: 10462363, PMCID: PMC3935822, DOI: 10.1002/hep.510300315.Peer-Reviewed Original ResearchConceptsFlorid duct lesionsPrimary biliary cirrhosisBile duct destructionDuct lesionsUrsodeoxycholic acidDuct destructionBiliary cirrhosisPlacebo-controlled trialNeedle biopsy specimensUDCA patientsAdvanced diseasePlacebo medicationEarly diseaseBiopsy specimensPatientsLesionsBeneficial effectsPathology literaturePrevalenceCirrhosisPlaceboMedicationsDiseaseYearsHepatopathologistBiliary 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
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 ResearchMeSH KeywordsAdultBileBilirubinDouble-Blind MethodFemaleHumansLiverLiver Cirrhosis, BiliaryMaleMiddle AgedPlacebosTime FactorsTreatment FailureUrsodeoxycholic AcidConceptsPrimary biliary cirrhosisSerum bilirubinBiliary cirrhosisStratum 1Advanced primary biliary cirrhosisPlacebo-controlled trialBile acid poolLiver histologyPrognostic factorsTreatment failureSingle doseUrsodeoxycholic acidSevere symptomsPatientsUrsodiolLaboratory testsPlaceboHistologyBilirubinCirrhosisBiochemical testsGood responseStratum 3Acid poolLess effect
1994
Primary biliary cirrhosis: survival of a large cohort of symptomatic and asymptomatic patients followed for 24 years
Mahl T, Shockcor W, Boyer J. Primary biliary cirrhosis: survival of a large cohort of symptomatic and asymptomatic patients followed for 24 years. Journal Of Hepatology 1994, 20: 707-713. PMID: 7930469, DOI: 10.1016/s0168-8278(05)80139-4.Peer-Reviewed Original ResearchMeSH KeywordsFemaleFollow-Up StudiesHumansLife TablesLiver Cirrhosis, BiliaryMaleMiddle AgedMultivariate AnalysisRisk FactorsSurvival AnalysisConceptsTime of diagnosisAsymptomatic patientsSurvival of patientsGender-matched control populationPrimary biliary cirrhosisMedian followElevated bilirubinOverall survivalSymptomatic patientsAdvanced fibrosisBile stasisBiliary cirrhosisIndependent predictorsLiver biopsyLiver diseaseDiminished survivalLarge cohortPatientsOriginal diagnosisAccurate followControl populationSymptomsSurvival dataDiagnosisSurvival
1992
The natural history of primary biliary cirrhosis.
Boyer J, Shockcor W, Mahl T. The natural history of primary biliary cirrhosis. Transactions Of The American Clinical And Climatological Association 1992, 103: 157-63. PMID: 1413375, PMCID: PMC2376687.Peer-Reviewed Original Research
1985
Asymptomatic primary biliary cirrhosis A progress report on long-term follow-up and natural history
Beswick D, Klatskin G, Boyer J. Asymptomatic primary biliary cirrhosis A progress report on long-term follow-up and natural history. Gastroenterology 1985, 89: 267-271. PMID: 4007417, DOI: 10.1016/0016-5085(85)90325-7.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAutoimmune DiseasesBilirubinBiopsyFemaleFollow-Up StudiesGranulomaHepatomegalyHumansLiver Cirrhosis, BiliaryMaleMiddle AgedConceptsAsymptomatic primary biliary cirrhosisPrimary biliary cirrhosisBiliary cirrhosisAsymptomatic stateGeneral populationInitial liver biopsySubgroup of patientsLife table survival analysisDevelopment of symptomsMedian followPortal granulomasOverall survivalProgressive diseaseLiver biopsyLiver diseaseMedian periodAutoimmune disordersExtended followHistologic featuresBenign outcomeCirrhosisPatientsSurvival analysisNatural historySymptoms
1984
Primary Biliary Cirrhosis
Beswick D, Boyer J. Primary Biliary Cirrhosis. Hepatology 1984, 4: 29s-32s. PMID: 6363257, DOI: 10.1002/hep.1840040710.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsHumansLiver Cirrhosis, BiliaryLiver TransplantationNational Institutes of Health (U.S.)PrognosisUnited States
1983
The Prognostic Importance of Clinical and Histologic Features in Asymptomatic and Symptomatic Primary Biliary Cirrhosis
Roll J, Boyer J, Barry D, Klatskin G. The Prognostic Importance of Clinical and Histologic Features in Asymptomatic and Symptomatic Primary Biliary Cirrhosis. New England Journal Of Medicine 1983, 308: 1-7. PMID: 6847917, DOI: 10.1056/nejm198301063080101.Peer-Reviewed Original ResearchConceptsPrimary biliary cirrhosisBiliary cirrhosisPoor prognosisSymptomatic primary biliary cirrhosisOnset of diseaseAsymptomatic patientsAsymptomatic diseaseClinical featuresHistologic featuresHistologic stagePrediction of riskPrognostic importanceSerum bilirubinHepatic fibrosisHistologic findingsPortal areasProlonged survivalMultivariate analysisPatientsControl populationPrognosisWeight lossElevated levelsLife expectancySurvival data
1980
Bone disease in primary biliary cirrhosis: Reversal of osteomalacia with oral 25-hydroxyvitamin D
Reed J, Meredith S, Nemchausky B, Rosenberg I, Boyer J. Bone disease in primary biliary cirrhosis: Reversal of osteomalacia with oral 25-hydroxyvitamin D. Gastroenterology 1980, 78: 512-517. PMID: 7351289, DOI: 10.1016/0016-5085(80)90865-3.Peer-Reviewed Original ResearchMeSH KeywordsAdultBiopsyBone and BonesFemaleHumansHydroxycholecalciferolsLiver Cirrhosis, BiliaryMiddle AgedOsteomalaciaConceptsPrimary biliary cirrhosisBiliary cirrhosisBone biopsyBone diseaseIliac crest bone biopsiesMineralized bone massVitamin D deficiencyRelative osteoid volumeCrest bone biopsiesTrabecular bone volumeLow serum concentrationsD deficiencyD therapySerum concentrationsOsteoid volumeBone massTreatment periodOsteoid surfaceBone volumeOsteomalaciaHistomorphometric analysisCirrhosisPatientsBone mineralizationBiopsy
1979
Phenobarbital treatment in primary biliary cirrhosis. Differences in bile acid composition between responders and nonresponders.
Stellaard F, Bolt M, Boyer J, Klein P. Phenobarbital treatment in primary biliary cirrhosis. Differences in bile acid composition between responders and nonresponders. Translational Research 1979, 94: 853-61. PMID: 501209.Peer-Reviewed Original ResearchNonalcoholic liver disease Overlooked causes of liver injury in patients with heavy alcohol consumption
Levin D, Baker A, Riddell R, Rochman H, Boyer J. Nonalcoholic liver disease Overlooked causes of liver injury in patients with heavy alcohol consumption. The American Journal Of Medicine 1979, 66: 429-434. PMID: 433949, DOI: 10.1016/0002-9343(79)91064-7.Peer-Reviewed Original ResearchConceptsAlcoholic liver diseaseNonalcoholic liver diseaseLiver diseaseLiver biopsyHeavy alcohol consumptionAlcohol consumptionHepatitis B surface antigenSerum glutamic oxaloacetic transaminaseB surface antigenGlutamic oxaloacetic transaminaseAcute hepatitisChronic hepatitisTransaminase ratioConsecutive patientsLiver injuryAppropriate therapyClinical featuresLiver disordersOverlooked causeAlcoholic subjectsPatientsSurface antigenOxaloacetic transaminaseBiopsyDisease