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 cholangitisProtocol for the development of a core outcome set for clinical trials in primary sclerosing cholangitis
Hussain N, Ma C, Hirschfield G, Walmsley M, Hanford P, Vesterhus M, Kowdley K, Bergquist A, Ponsioen C, Levy C, Assis D, Schramm C, Bowlus C, Trauner M, Aiyegbusi O, Jairath V, Trivedi P. Protocol for the development of a core outcome set for clinical trials in primary sclerosing cholangitis. BMJ Open 2024, 14: e080143. PMID: 38926149, PMCID: PMC11216047, DOI: 10.1136/bmjopen-2023-080143.Peer-Reviewed Original ResearchConceptsPrimary sclerosing cholangitisClinical trialsSclerosing cholangitisCore outcome setImmune-mediated liver diseasesPrimary sclerosing cholangitis treatmentOutcome measuresEvaluate novel therapiesSlow disease progressionPatient-reported outcome measuresMedical therapyNovel therapiesLiver fibrosisDisease progressionHistological assessmentLiver diseaseInternational two-round Delphi surveyImaging-based biomarkersIntervention trialsTherapyConsensus meetingHealthcare payersCholangitisSemistructured qualitative interviewsTwo-round Delphi surveyAfrican American race does not confer an increased risk of clinical events in patients with primary sclerosing cholangitis.
Yazdanfar M, Zepeda J, Dean R, Wu J, Levy C, Goldberg D, Lammert C, Prenner S, Reddy K, Pratt D, Forman L, Assis D, Lytvyak E, Montano-Loza A, Gordon S, Carey E, Ahn J, Schlansky B, Korzenik J, Karagozian R, Hameed B, Chandna S, Yu L, Bowlus C. African American race does not confer an increased risk of clinical events in patients with primary sclerosing cholangitis. Hepatology Communications 2024, 8 PMID: 38285883, PMCID: PMC10830082, DOI: 10.1097/hc9.0000000000000366.Peer-Reviewed Original ResearchConceptsPrimary sclerosing cholangitisTransplant-free survivalInflammatory bowel diseaseHepatic decompensationNon-Hispanic whitesSclerosing cholangitisIncreased risk of clinical eventsNatural history of primary sclerosing cholangitisAssociated with transplant-free survivalHistory of primary sclerosing cholangitisAssociated with hepatic decompensationBowel diseaseProgression to hepatic decompensationRisk of clinical eventsDecompensation-free survivalMayo risk scoreAbnormal liver testsPerformance of prognostic modelsAfrican American raceRates of inflammatory bowel diseaseDeath/liver transplantationAA patientsLiver testsDiagnostic delayAA race
2023
WED-283 Investigating the cholestatic pruritus of primary sclerosing cholangitis (ItCh-PSC): a study of patients participating in the consortium for autoimmune liver disease (CALiD)
Dean R, Yazdanfar M, Zepeda J, Levy C, Gordon S, Forman L, Lammert C, Assis D, Pratt D, Gungabissoon U, McGirr A, Mukherjee S, McLaughlin M, Bowlus C. WED-283 Investigating the cholestatic pruritus of primary sclerosing cholangitis (ItCh-PSC): a study of patients participating in the consortium for autoimmune liver disease (CALiD). Journal Of Hepatology 2023, 78: s388. DOI: 10.1016/s0168-8278(23)01040-1.Peer-Reviewed Original ResearchRecent Advances in the Management of Primary Sclerosing Cholangitis
Assis D, Bowlus C. Recent Advances in the Management of Primary Sclerosing Cholangitis. Clinical Gastroenterology And Hepatology 2023, 21: 2065-2075. PMID: 37084929, DOI: 10.1016/j.cgh.2023.04.004.Peer-Reviewed Original ResearchConceptsChronic cholestatic liver diseasePrimary sclerosing cholangitisInflammatory bowel diseasePrognostication of patientsCholestatic liver diseaseSclerosing cholangitisBowel diseaseLiver failureClinical featuresLiver diseaseMedical managementBiliary treeComplex pathophysiologyEffective therapyPharmacologic agentsRare natureCurrent conceptsDiseaseCholangitisFurther studiesCholangiocarcinomaPatientsPathophysiologyTherapyPrognosticationOutcomes of immunomodulator and advanced therapies for primary sclerosing cholangitis-associated inflammatory bowel disease
Sayed A, Assis D, Silveira M, Deng Y, Ciarleglio M, Gaidos J, Proctor D, Al-Bawardy B. Outcomes of immunomodulator and advanced therapies for primary sclerosing cholangitis-associated inflammatory bowel disease. European Journal Of Gastroenterology & Hepatology 2023, 35: 270-274. PMID: 36708297, DOI: 10.1097/meg.0000000000002510.Peer-Reviewed Original ResearchConceptsPrimary sclerosing cholangitisInflammatory bowel diseasePSC-IBDEndoscopic healingTherapy groupAdvanced therapiesClinical remissionBowel diseaseAcute ascending cholangitisRate of cholangitisSmall bowel involvementThird of patientsAscending cholangitisSclerosing cholangitisAdult patientsBowel involvementSecondary outcomesMedian agePrimary outcomeRetrospective studyHigh riskCholangitisPatientsTherapyLarger study
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 patientsPREDICTORS AND OUTCOMES OF BIOLOGIC/IMMUNOSUPPRESSIVE THERAPY FOR PSC-ASSOCIATED IBD
Sayed A, Silveira M, Assis D, Deng Y, Gaidos J, Proctor D, Al-Bawardy B. PREDICTORS AND OUTCOMES OF BIOLOGIC/IMMUNOSUPPRESSIVE THERAPY FOR PSC-ASSOCIATED IBD. Inflammatory Bowel Diseases 2022, 28: s76-s76. DOI: 10.1093/ibd/izac015.124.Peer-Reviewed Original ResearchPrimary sclerosing cholangitisInflammatory bowel diseasePSC-IBDSmall bowel involvementClinical remissionEndoscopic healingIMM groupAutoimmune hepatitisBowel involvementUrsodeoxycholic acidExact testBackground Inflammatory bowel diseaseEpisodes of cholangitisRate of cholangitisThird of patientsUnpaired Student's t-testFisher's exact testT-testSmall molecule therapiesStudent's t-testThiopurine monotherapyImmunosuppressive therapySclerosing cholangitisAdult patientsBiologic therapy
2021
Oral Vancomycin or Ursodeoxycholic Acid for Pediatric Primary Sclerosing Cholangitis? The Uncontroversial Need for Randomized Controlled Trials
Assis DN, Levy C. Oral Vancomycin or Ursodeoxycholic Acid for Pediatric Primary Sclerosing Cholangitis? The Uncontroversial Need for Randomized Controlled Trials. Hepatology 2021, 73: 887-889. PMID: 33403699, DOI: 10.1002/hep.31702.Peer-Reviewed Original Research
2020
A Systematic Review of Patient‐Reported Outcomes in Primary Biliary Cholangitis and Primary Sclerosing Cholangitis
Kim HP, Lieber SR, Rogers ME, Moon AM, Loiselle M, Walker J, Assis DN, Safer R, Gomel R, Evon DM. A Systematic Review of Patient‐Reported Outcomes in Primary Biliary Cholangitis and Primary Sclerosing Cholangitis. Hepatology Communications 2020, 4: 1502-1515. PMID: 33024919, PMCID: PMC7527768, DOI: 10.1002/hep4.1567.Peer-Reviewed Original ResearchPrimary biliary cholangitisPrimary sclerosing cholangitisHealth-related qualityPRO instrumentsPRO conceptsSclerosing cholangitisAdverse eventsBiliary cholangitisSystematic reviewDecreased health-related qualityPhysical adverse eventsGastrointestinal adverse eventsNumeric rating scaleTarget populationStudy populationVisual analogueCholangitisPatient experiencePsychometric testingPatient validationStudy outcomesRating ScaleDescriptive statisticsOutcome conceptsOutcomesFenofibrate 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 cellsEffects of Vedolizumab in Patients With Primary Sclerosing Cholangitis and Inflammatory Bowel Diseases
Lynch KD, Chapman RW, Keshav S, Montano-Loza AJ, Mason AL, Kremer AE, Vetter M, de Krijger M, Ponsioen CY, Trivedi P, Hirschfield G, Schramm C, Liu CH, Bowlus CL, Estes DJ, Pratt D, Hedin C, Bergquist A, de Vries AC, van der Woude CJ, Yu L, Assis DN, Boyer J, Ytting H, Hallibasic E, Trauner M, Marschall HU, Daretti LM, Marzioni M, Yimam KK, Perin N, Floreani A, Beretta-Piccoli BT, Rogers JK, Group I, Levy C. Effects of Vedolizumab in Patients With Primary Sclerosing Cholangitis and Inflammatory Bowel Diseases. Clinical Gastroenterology And Hepatology 2019, 18: 179-187.e6. PMID: 31100458, PMCID: PMC6941216, DOI: 10.1016/j.cgh.2019.05.013.Peer-Reviewed Original ResearchConceptsPrimary sclerosing cholangitisInflammatory bowel diseaseEffect of vedolizumabSerum levelsLast followSclerosing cholangitisBowel diseaseStudy groupInternational PSC Study GroupAlkaline phosphataseLiver-related eventsLiver-related outcomesPresence of cirrhosisProportion of patientsSubset of patientsMedian serum levelsAnalysis of patientsInternational Study GroupLarge international cohortNorth American centersBacterial cholangitisCirrhosis decompensationEntire cohortClinical dataIntegrin α4β7Patient-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
Mo1444 Prevalence of Primary Sclerosing Cholangitis in Black Patients: Results of a Multi-Center North American Consortium
Goldberg D, Yimam K, Eksteen B, Levy C, Pratt D, Schwarz K, Forman L, Yu L, Rahimi R, Assis D, Bowlus C. Mo1444 Prevalence of Primary Sclerosing Cholangitis in Black Patients: Results of a Multi-Center North American Consortium. Gastroenterology 2017, 152: s1185. DOI: 10.1016/s0016-5085(17)33954-9.Peer-Reviewed Original ResearchPrimary sclerosing cholangitisNorth American ConsortiumSclerosing cholangitisBlack patientsAmerican ConsortiumCholangitisPatientsCombination 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 failure