2024
Fecal deoxycholic acid associates with diet, intestinal microbes, and total bilirubin in primary sclerosing cholangitis
Chan C, Lemos M, Finnegan P, Gagnon W, Dean R, Yazdanafar M, Zepeda J, Vohl M, Trauner M, Korzenik J, Barbier O, Marco M, Bowlus C. Fecal deoxycholic acid associates with diet, intestinal microbes, and total bilirubin in primary sclerosing cholangitis. JHEP Reports 2024, 6: 101188. DOI: 10.1016/j.jhepr.2024.101188.Peer-Reviewed Original ResearchPrimary sclerosing cholangitisMarkers of BA synthesisFecal deoxycholic acidInflammatory bowel diseaseCholestatic liver diseaseFarnesoid X receptorFarnesoid X receptor activationSclerosing cholangitisDisease progressionFecal bile acidsTotal bilirubinDuct primary sclerosing cholangitisBile acidsLiver diseaseMarker of clinical outcomeBA synthesisChronic cholestatic liver diseaseRRNA gene sequencesUrsodeoxycholic acid useDeoxycholic acidAbundance of BlautiaMarkers of disease progressionVariable disease progressionAssociated with total bilirubinSerum total bilirubinCorrection to COBALT: A Confirmatory Trial of Obeticholic Acid in Primary Biliary Cholangitis With Placebo and External Controls.
Kowdley K, Hirschfield G, Coombs C, Malecha E, Bessonova L, Li J, Rathnayaka N, Mells G, Jones D, Trivedi P, Hansen B, Smith R, Wason J, Hiu S, Kareithi D, Mason A, Bowlus C, Muller K, Carbone M, Berenguer M, Milkiewicz P, Adekunle F, Villamil A. Correction to COBALT: A Confirmatory Trial of Obeticholic Acid in Primary Biliary Cholangitis With Placebo and External Controls. The American Journal Of Gastroenterology 2024 PMID: 39621001, DOI: 10.14309/ajg.0000000000003153.Peer-Reviewed Original ResearchPrimary Biliary Cholangitis: Personalizing Second-Line Therapies-R1
Levy C, Bowlus C. Primary Biliary Cholangitis: Personalizing Second-Line Therapies-R1. Hepatology 2024 DOI: 10.1097/hep.0000000000001166.Peer-Reviewed Original ResearchPrimary biliary cholangitisSecond-line agentsUrsodeoxycholic acidInadequate response to UDCAResponse to UDCADiagnosis of primary biliary cholangitisDisease progressionTreatment of primary biliary cholangitisRisk of disease progressionLong-term clinical outcomesProgression to biliary cirrhosisCohort study of patientsPeroxisome proliferator-activated receptor agonistsSecond-line therapyOff-label therapyAnti-mitochondrial antibodiesIntralobular bile ductsSymptoms of pruritusStudy of patientsBile acid physiologyDelay disease progressionSerum alkaline phosphataseMiddle-aged womenImprove cholestasisLiver biochemistryAnti-integrin αvβ6 autoantibodies are increased in PSC patients with concomitant IBD and correlate with liver disease severity
Bloemen H, Livanos A, Martins A, Dean R, Bravo A, Bourgonje A, Tankelevich M, Herb J, Cho J, Santos A, Rodrigues C, Petralia F, Colombel J, Bowlus C, Schiano T, Torres J, Levy C, Mehandru S. Anti-integrin αvβ6 autoantibodies are increased in PSC patients with concomitant IBD and correlate with liver disease severity. Clinical Gastroenterology And Hepatology 2024 PMID: 39490950, DOI: 10.1016/j.cgh.2024.10.005.Peer-Reviewed Original ResearchPrimary sclerosing cholangitis patientsPrimary sclerosing cholangitisLiver disease severityConcomitant inflammatory bowel diseaseInflammatory bowel diseaseHealthy controlsEnzyme-linked immunosorbent assayDisease severityAssociated with liver disease severityUlcerative colitisAssociated with markers of systemic inflammationMayo PSC risk scoreMarkers of systemic inflammationMarkers of liver disease severityLiver stiffness measurementMultivariate linear regression analysisAlkaline phosphatase levelsAssociated with markersInflammatory bowel disease subtypePSC patientsSclerosing cholangitisInflammation panelSystemic inflammationPSC-UCPSC-IBDP21 Improvement in lipid profiles with elafibranor treatment in primary biliary cholangitis during the phase III ELATIVE® trial
Mayo M, Antunes N, Pedersen M, Tonev D, Shu J, Bowlus C, Kowdley K, Zein C, Levy C. P21 Improvement in lipid profiles with elafibranor treatment in primary biliary cholangitis during the phase III ELATIVE® trial. 2024, a22.2-a23. DOI: 10.1136/gutjnl-2024-basl.32.Peer-Reviewed Original ResearchS178 Obeticholic Acid Normalizes Inflammatory Biomarkers in Patients With Primary Biliary Cholangitis
Foston T, Jones D, Bowlus C, Thranian A, Erickson M, Li J, Gasink C, Gish R. S178 Obeticholic Acid Normalizes Inflammatory Biomarkers in Patients With Primary Biliary Cholangitis. The American Journal Of Gastroenterology 2024, 119: s129-s129. DOI: 10.14309/01.ajg.0001029080.26092.00.Peer-Reviewed Original ResearchS1881 Long-Term Efficacy and Safety of Open-Label Seladelpar Treatment in Patients With Primary Biliary Cholangitis: Interim Results for 2 Years From the ASSURE Study
Trivedi P, Levy C, Kowdley K, Gordon S, Bowlus C, Hurtado M, Hirschfield G, Gulamhusien A, Lawitz E, Villamil A, de Guevara Cetina A, Mayo M, Younes Z, Shibolet O, Yimam K, Pratt D, Heo J, Morgera U, Andreone P, Kremer A, Corpechot C, Goel A, Peyton A, Elbeshbeshy H, Crittenden D, Heusner C, Proehl S, Zhou S, McWherter C. S1881 Long-Term Efficacy and Safety of Open-Label Seladelpar Treatment in Patients With Primary Biliary Cholangitis: Interim Results for 2 Years From the ASSURE Study. The American Journal Of Gastroenterology 2024, 119: s1351-s1352. DOI: 10.14309/01.ajg.0001036892.89042.29.Peer-Reviewed Original ResearchCOBALT: A Confirmatory Trial of Obeticholic Acid in Primary Biliary Cholangitis With Placebo and External Controls.
Kowdley K, Hirschfield G, Coombs C, Malecha E, Bessonova L, Li J, Rathnayaka N, Mells G, Jones D, Trivedi P, Hansen B, Smith R, Wason J, Hiu S, Kareithi D, Mason A, Bowlus C, Muller K, Carbone M, Berenguer M, Milkiewicz P, Adekunle F, Villamil A. COBALT: A Confirmatory Trial of Obeticholic Acid in Primary Biliary Cholangitis With Placebo and External Controls. The American Journal Of Gastroenterology 2024 PMID: 39140490, DOI: 10.14309/ajg.0000000000003029.Peer-Reviewed Original ResearchPrimary biliary cholangitisObeticholic acidClinical outcomesFunctional unblindingPlacebo armBiliary cholangitisConfirmatory trialsUS healthcare claims databasePrimary biliary cholangitis patientsOCA therapyObeticholic acid treatmentPrimary composite endpointAs-treated analysisHealthcare claims databaseNegative clinical outcomesUncontrolled ascitesPlacebo patientsHepatic decompensationPrimary endpointLiver transplantationComposite endpointCommercial therapySafety signalsPlaceboTreatment crossoverSerologic extracellular matrix remodeling markers are related to fibrosis stage and prognosis in a phase 2b trial of simtuzumab in patients with primary sclerosing cholangitis
Thorburn D, Leeming D, Barchuk W, Wang Y, Lu X, Malkov V, Ito K, Bowlus C, Levy C, Goodman Z, Karsdal M, Muir A, Xu J. Serologic extracellular matrix remodeling markers are related to fibrosis stage and prognosis in a phase 2b trial of simtuzumab in patients with primary sclerosing cholangitis. Hepatology Communications 2024, 8: e0467. PMID: 38967589, PMCID: PMC11227354, DOI: 10.1097/hc9.0000000000000467.Peer-Reviewed Original ResearchConceptsPrimary sclerosing cholangitisELF scoreAdvanced fibrosisFibrosis stageFibrosis progressionClinical eventsSclerosing cholangitisExtracellular matrix remodeling markersRemodeling markersPredictors of disease severityPhase 2b trialBaseline to weekPRO-C3Progression to cirrhosisWilcoxon rank sum testMarker of collagen formationType III procollagenModerate diagnostic abilityDiagnosing fibrosis stagesRank sum testSerum markersNoninvasive predictorPrognostic markerModerate prognosisMedian changeProtocol 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 surveyTHU-132 Obeticholic acid normalizes inflammatory biomarkers in patients with primary biliary cholangitis
Jones D, Bowlus C, Thranian A, Erickson M, Li J, Gasink C, Gish R. THU-132 Obeticholic acid normalizes inflammatory biomarkers in patients with primary biliary cholangitis. Journal Of Hepatology 2024, 80: s325. DOI: 10.1016/s0168-8278(24)01116-4.Peer-Reviewed Original ResearchTHU-105 Improvement in lipid profiles with elafibranor treatment in primary biliary cholangitis during the phase III Elativetrial
Mayo M, Antunes N, Pedersen M, Tonev D, Shu J, Bowlus C, Kowdley K, Zein C, Levy C. THU-105 Improvement in lipid profiles with elafibranor treatment in primary biliary cholangitis during the phase III Elativetrial. Journal Of Hepatology 2024, 80: s312-s313. DOI: 10.1016/s0168-8278(24)01090-0.Peer-Reviewed Original ResearchLBP-039 Oral alpha-v/beta-6 and alpha-v/beta-1 integrin inhibitor bexotegrast in primary sclerosing cholangitis: updated 12-week interim safety and efficacy analysis of the INTEGRIS-PSC phase 2a trial
Trauner M, Kowdley K, Hirschfield G, Lefebvre E, Decaris M, Schaub J, Clark A, Lin M, An M, Balasubramanyam A, Barnes C, Pencek R, Thorburn D, Montano-Loza A, Bowlus C, Schramm C, Levy C, Trivedi P. LBP-039 Oral alpha-v/beta-6 and alpha-v/beta-1 integrin inhibitor bexotegrast in primary sclerosing cholangitis: updated 12-week interim safety and efficacy analysis of the INTEGRIS-PSC phase 2a trial. Journal Of Hepatology 2024, 80: s97-s98. DOI: 10.1016/s0168-8278(24)00606-8.Peer-Reviewed Original ResearchPatient-focused drug development in primary sclerosing cholangitis: Insights on patient priorities and involvement in clinical trials
Li M, Pai R, Gomel R, Vyas M, Callif S, Hatchett J, Bowlus C, Lai J. Patient-focused drug development in primary sclerosing cholangitis: Insights on patient priorities and involvement in clinical trials. Hepatology Communications 2024, 8: e0433. PMID: 38727680, PMCID: PMC11093571, DOI: 10.1097/hc9.0000000000000433.Peer-Reviewed Original ResearchConceptsPrimary sclerosing cholangitisClinical trialsSclerosing cholangitisDrug trialsTrial participantsMultivariate logistic regressionAssociated with willingnessInflammatory bowel diseaseLong-term riskReferral of patientsDrug developmentTherapy trialsDisease progressionTrial interestBowel diseasePatient-focused drug developmentTreatment trialsPatientsBiopsy requirementsPruritusPatient interestPredictors of patients' willingnessLogistic regressionCholangitisPatients' willingnessAssessment of fatigue and its impact in chronic liver disease
Younossi Z, Kremer A, Swain M, Jones D, Bowlus C, Trauner M, Henry L, Gerber L. Assessment of fatigue and its impact in chronic liver disease. Journal Of Hepatology 2024, 81: 726-742. PMID: 38670320, DOI: 10.1016/j.jhep.2024.04.008.Peer-Reviewed Original ResearchLevels of fatigueHealth related qualityBurden of chronic liver diseaseRelated qualityHepatitis C viral infectionPatients' health related qualityImpact of fatiguePrimary biliary cholangitisAssessment of fatigueChronic liver diseaseExpert reviewComplexity of fatigueSelf-report instrumentImproved HRQLPRO dataSelf-report measuresHRQLLiver diseaseOutcome measuresPeripheral causesChronic hepatitis C viral infectionChronic liver disease severityComprehensive burdenStage of chronic liver diseasePresence of cirrhosisImpact of itch on quality of life in people with primary biliary cholangitis: A plain language summary
Mayo M, Carey E, Smith H, Mospan A, McLaughlin M, Thompson A, Morris H, Sandefur R, Bowlus C, Investigators O, Levy C. Impact of itch on quality of life in people with primary biliary cholangitis: A plain language summary. Future Rare Diseases 2024, 0 DOI: 10.2217/frd-2023-0016.Peer-Reviewed Original ResearchPrimary biliary cholangitisSignificant itchBiliary cholangitisMild itchImpact of itchQuality of lifeTreatment guidelinesTreatment optionsWorse scoresItchPerson's qualityItchingMedicationsPerson's sleepSleepCholangitisWorse qualitySymptomsOne-thirdPoor qualityProfessional societiesGuidelinesHigh levelsLifeDiseaseA Phase 3 Trial of Seladelpar in Primary Biliary Cholangitis
Hirschfield G, Bowlus C, Mayo M, Kremer A, Vierling J, Kowdley K, Levy C, Villamil A, Ladrón de Guevara Cetina A, Janczewska E, Zigmond E, Jeong S, Yilmaz Y, Kallis Y, Corpechot C, Buggisch P, Invernizzi P, Londoño Hurtado M, Bergheanu S, Yang K, Choi Y, Crittenden D, McWherter C. A Phase 3 Trial of Seladelpar in Primary Biliary Cholangitis. New England Journal Of Medicine 2024, 390: 783-794. PMID: 38381664, DOI: 10.1056/nejmoa2312100.Peer-Reviewed Original ResearchConceptsPrimary biliary cholangitisAlkaline phosphatase levelsPruritus Numerical Rating ScalePercentage of patientsNumerical rating scaleBiliary cholangitisAdverse eventsPhosphatase levelsPlacebo groupUrsodeoxycholic acidPeroxisome proliferator-activated receptor delta agonistBaseline to month 6Severity of adverse eventsAlkaline phosphatase normalizationModerate-to-severe pruritusPlacebo-controlled trialPhase 3 trialUnacceptable side effectsRating ScaleBiochemical responsesBackground therapyDouble-blindDelta agonistsBilirubin levelsMonth 6Per-oral cholangioscopy in patients with primary sclerosing cholangitis: a 12-month follow-up study
Mohamed R, Tejaswi S, Aabakken L, Ponsioen C, Bowlus C, Adler D, Forbes N, Paulsen V, Voermans R, Urayama S, Peetermans J, Rousseau M, Eksteen B. Per-oral cholangioscopy in patients with primary sclerosing cholangitis: a 12-month follow-up study. Endoscopy International Open 2024, 12: e237-e244. PMID: 38362361, PMCID: PMC10869209, DOI: 10.1055/a-2236-7557.Peer-Reviewed Original ResearchEndoscopic retrograde cholangiographySerious adverse eventsPrimary sclerosing cholangitisLiver transplantationIndex procedurePSC patientsSclerosing cholangitisOral cholangioscopyRepeat endoscopic retrograde cholangiographyPrior liver transplantationCases of cholangiocarcinomaCCA incidencePrimary endpointSecondary endpointsAdverse eventsBiopsy findingsConsecutive patientsRetrograde cholangiographyAdditional patientsCytology findingsRepeat proceduresMean ageTherapeutic maneuversBenign cytologyCCA diagnosisHypercholesterolemia Is Associated With Dysregulation of Lipid Metabolism and Poor Prognosis in Primary Biliary Cholangitis
Zheng L, Tian S, Yang C, Li B, Jia G, Liu Y, Sun R, Wang X, Deng J, Zhang M, Cui L, Guo C, Zhou X, Leung P, Bowlus C, Gershwin M, Shang Y, Han Y. Hypercholesterolemia Is Associated With Dysregulation of Lipid Metabolism and Poor Prognosis in Primary Biliary Cholangitis. Clinical Gastroenterology And Hepatology 2024, 22: 1265-1274.e19. PMID: 38354969, DOI: 10.1016/j.cgh.2024.01.039.Peer-Reviewed Original ResearchPrimary biliary cholangitisPoor clinical outcomesAssociated with poor clinical outcomesHigh-risk patientsCirrhosis-related complicationsClinical outcomesTotal cholesterolBiliary cholangitisGLOBE scoreUntargeted lipidomicsLiver transplantationValidation cohortHealthy controlsRisk of poor clinical outcomesLipid metabolismBaseline total cholesterolComplete clinical dataLiver-related deathStratification of patientsAccurate stratification of patientsBaseline TC levelHigh-risk groupDysregulation of lipid metabolismAssociated with dysregulationUpregulated lipidsAfrican 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