2024
Correction 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 biochemistryP21 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 crossoverTHU-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 ResearchTHU-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 ResearchAssessment 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 cirrhosisA 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 6Hypercholesterolemia 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 lipids
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 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 acidImpact 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 2023, 4: frd50. 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 levelsLifeDiseaseOpen‐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 peroxisomePatients