2024
PPAR agonists for the treatment of cholestatic liver diseases: Over a decade of clinical progress
Hayes C, Gallucci G, Boyer J, Assis D, Ghonem N. PPAR agonists for the treatment of cholestatic liver diseases: Over a decade of clinical progress. Hepatology Communications 2024, 9: e0612. PMID: 39699308, PMCID: PMC11661771, DOI: 10.1097/hc9.0000000000000612.Peer-Reviewed Original ResearchConceptsPeroxisome proliferator-activated receptor agonistsPrimary biliary cholangitisPrimary sclerosing cholangitisPeroxisome proliferator-activated receptorUnited States Food and Drug Administration approvalHepatic accumulation of bile acidsRisk of progression to cirrhosisFood and Drug Administration approvalPeroxisome proliferator-activator receptor agonismSecond-line therapyFirst-line therapySymptoms of cholestasisDrug Administration approvalTreatment of cholestatic liver diseasesCholestatic liver diseaseAccumulation of bile acidsProgression to cirrhosisTreatment of cholestasisSignificant clinical interestSmall bile ductsProliferator-activated receptorsBile acid metabolismIncomplete respondersBiliary cholangitisBiliary stricturesPPAR-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
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 patientsEffects of immunosuppressive drugs on COVID-19 severity in patients with autoimmune hepatitis.
Efe C, Lammert C, Taşçılar K, Dhanasekaran R, Ebik B, Higuera-de la Tijera F, Calışkan AR, Peralta M, Gerussi A, Massoumi H, Catana AM, Purnak T, Rigamonti C, Aldana AJG, Khakoo N, Nazal L, Frager S, Demir N, Irak K, Melekoğlu-Ellik Z, Kacmaz H, Balaban Y, Atay K, Eren F, Alvares-da-Silva MR, Cristoferi L, Urzua Á, Eşkazan T, Magro B, Snijders R, Barutçu S, Lytvyak E, Zazueta GM, Demirezer-Bolat A, Aydın M, Heurgue-Berlot A, De Martin E, Ekin N, Yıldırım S, Yavuz A, Bıyık M, Narro GC, Kıyıcı M, Akyıldız M, Kahramanoğlu-Aksoy E, Vincent M, Carr RM, Günşar F, Reyes EC, Harputluoğlu M, Aloman C, Gatselis NK, Üstündağ Y, Brahm J, Vargas NCE, Güzelbulut F, Garcia SR, Aguirre J, Anders M, Ratusnu N, Hatemi I, Mendizabal M, Floreani A, Fagiuoli S, Silva M, Idilman R, Satapathy SK, Silveira M, Drenth JPH, Dalekos GN, Assis DN, Björnsson E, Boyer JL, Yoshida EM, Invernizzi P, Levy C, Montano-Loza AJ, Schiano TD, Ridruejo E, Wahlin S. Effects of immunosuppressive drugs on COVID-19 severity in patients with autoimmune hepatitis. Liver International : Official Journal Of The International Association For The Study Of The Liver 2022, 42: 607-614. PMID: 34846800, DOI: 10.1111/liv.15121.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 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 technologyPatientsPathophysiology
2020
AS055 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 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 cellsPatient-Derived Organoids from Human Bile: An In Vitro Method to Study Cholangiopathies
Soroka CJ, Assis DN, Boyer JL. Patient-Derived Organoids from Human Bile: An In Vitro Method to Study Cholangiopathies. Methods In Molecular Biology 2019, 1981: 363-372. PMID: 31016667, DOI: 10.1007/978-1-4939-9420-5_24.BooksConceptsPrimary sclerosing cholangitisPrimary sclerosing cholangitis patientsEndoscopic retrograde cholangiopancreatographySclerosing cholangitisCholangitis patientsRetrograde cholangiopancreatographyExtrahepatic bile duct epitheliumTherapeutic endoscopic retrograde cholangiopancreatographyChemo/cytokinesEnd-stage diseaseBile duct epitheliumPatient-derived organoidsPharmacotherapeutic treatmentClinical indicationsIndividual patientsInflammatory stimuliHeterogeneous diseaseBiliary phenotypeDuct epitheliumDisease statusCholangitisCholangiopathyHuman bileBiliary cellsPatients
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 levelsFRI-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 polymorphismsNow you see it, now you don't
Plotkin E, Assis D, Boyer J. Now you see it, now you don't. Hepatology 2013, 58: 446-447. DOI: 10.1002/hep.26439.Peer-Reviewed Original Research
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