2024
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. 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 crossoverFecal 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, 101188. DOI: 10.1016/j.jhepr.2024.101188.Peer-Reviewed Original ResearchSerologic 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-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 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 raceChapter 43 Primary sclerosing cholangitis and IgG4-associated cholangitis
Bowlus C. Chapter 43 Primary sclerosing cholangitis and IgG4-associated cholangitis. 2024, 845-868. DOI: 10.1016/b978-0-443-23947-2.00020-5.Peer-Reviewed Original ResearchIgG4-associated cholangitisPrimary sclerosing cholangitisInflammatory bowel diseaseAssociated with inflammatory bowel diseaseFeatures of primary sclerosing cholangitisResponse to corticosteroidsSclerosing cholangitisClinical featuresInflammatory disordersBiliary treeBowel diseaseNatural historyOlder menCholangitisYoung adults
2023
Featured Cover
Mayo M, Vierling J, Bowlus C, Levy C, Hirschfield G, Neff G, Galambos M, Gordon S, Borg B, Harrison S, Thuluvath P, Goel A, Shiffman M, Swain M, Jones D, Trivedi P, Kremer A, Aspinall R, Sheridan D, Dörffel Y, Yang K, Choi Y, McWherter C. Featured Cover. Alimentary Pharmacology & Therapeutics 2023, 59: i-i. DOI: 10.1111/apt.17864.Peer-Reviewed Original ResearchEditorial: The evolving paradigms and treatments for primary biliary cholangitis—Authors' reply
Mayo M, Vierling J, Bowlus C. Editorial: The evolving paradigms and treatments for primary biliary cholangitis—Authors' reply. Alimentary Pharmacology & Therapeutics 2023, 59: 282-282. PMID: 38153281, DOI: 10.1111/apt.17798.Peer-Reviewed Original ResearchSeladelpar treatment reduces IL-31 and pruritus in patients with primary biliary cholangitis
Kremer A, Mayo M, Hirschfield G, Levy C, Bowlus C, Jones D, Johnson J, McWherter C, Choi Y. Seladelpar treatment reduces IL-31 and pruritus in patients with primary biliary cholangitis. Hepatology 2023, 80: 27-37. PMID: 38117036, PMCID: PMC11191048, DOI: 10.1097/hep.0000000000000728.Peer-Reviewed Original ResearchAnti-pruritic effectsIL-31 levelsPrimary biliary cholangitisBile acid levelsIL-31PBC patientsBile acidsPruritus improvementBiliary cholangitisInterleukin-31Acid levelsIL-31 signalingSerum IL-31Pruritic skin diseaseDaily oral dosesSerum bile acidsNumerical rating scaleTotal bile acidsDose-dependent reductionPPAR-delta agonistOral dosesENHANCE studyPruritusHealthy volunteersPatientsEfficacy and Safety of Elafibranor in Primary Biliary Cholangitis
Kowdley K, Bowlus C, Levy C, Akarca U, Alvares-da-Silva M, Andreone P, Arrese M, Corpechot C, Francque S, Heneghan M, Invernizzi P, Jones D, Kruger F, Lawitz E, Mayo M, Shiffman M, Swain M, Valera J, Vargas V, Vierling J, Villamil A, Addy C, Dietrich J, Germain J, Mazain S, Rafailovic D, Taddé B, Miller B, Shu J, Zein C, Schattenberg J. Efficacy and Safety of Elafibranor in Primary Biliary Cholangitis. New England Journal Of Medicine 2023, 390: 795-805. PMID: 37962077, DOI: 10.1056/nejmoa2306185.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAlkaline PhosphataseBilirubinChalconesCholagogues and CholereticsCholestasisDouble-Blind MethodGastrointestinal AgentsHumansLiver Cirrhosis, BiliaryPeroxisome Proliferator-Activated ReceptorsPPAR alphaPPAR deltaPropionatesPruritusTreatment OutcomeUrsodeoxycholic AcidConceptsPrimary biliary cholangitisBiliary cholangitisAlkaline phosphatase levelsPeroxisome proliferator-activated receptorPhosphatase levelsDual peroxisome proliferator-activated receptorLeast-squares mean changeChronic cholestatic liver diseaseItch Numeric Rating ScaleDestruction of interlobular bile ductsModerate-to-severe pruritusPlacebo-controlled trialCholestatic liver diseaseNumerical rating scaleInterlobular bile ductsWorst Itch Numeric Rating ScaleIndicator of cholestasisProliferator-activated receptorsAbdominal painDouble-blindPlacebo groupRelevant biochemical indicatorsAdverse eventsPruritus intensityUrsodeoxycholic acidOpen‐label, clinical trial extension: Two‐year safety and efficacy results of seladelpar in patients with primary biliary cholangitis
Mayo M, Vierling J, Bowlus C, Levy C, Hirschfield G, Neff G, Galambos M, Gordon S, Borg B, Harrison S, Thuluvath P, Goel A, Shiffman M, Swain M, Jones D, Trivedi P, Kremer A, Aspinall R, Sheridan D, Dörffel Y, Yang K, Choi Y, McWherter C. Open‐label, clinical trial extension: Two‐year safety and efficacy results of seladelpar in patients with primary biliary cholangitis. Alimentary Pharmacology & Therapeutics 2023, 59: 186-200. PMID: 37904314, DOI: 10.1111/apt.17755.Peer-Reviewed Original ResearchConceptsPrimary biliary cholangitisBiliary cholangitisLiver injurySerious treatment-related adverse eventsBiochemical markersLong-term extension studyTreatment-related adverse eventsAnti-pruritic effectsClinical trial extensionsSecondary efficacy analysesTwo-Year SafetyUnexpected histological findingsNon-alcoholic steatohepatitisLong-term safetyAdverse eventsElevated bilirubinComposite endpointDose adjustmentEfficacy analysisHistological findingsTrial extensionEfficacy dataEfficacy resultsSelective peroxisomePatientsYIELD OF EARLY PER-ORAL CHOLANGIOSCOPY IN PATIENTS WITH PRIMARY SCLEROSING CHOLANGITIS
Mohamed R, Forbes N, Aabakken L, Paulsen V, Ponsioen C, Voermans R, Tejaswi S, Bowlus C, Urayama S, Adler D, Peetermans J, Rousseau M, Eksteen B. YIELD OF EARLY PER-ORAL CHOLANGIOSCOPY IN PATIENTS WITH PRIMARY SCLEROSING CHOLANGITIS. Gastrointestinal Endoscopy 2023, 97: ab592. DOI: 10.1016/j.gie.2023.04.979.Peer-Reviewed Original Research