2023
Organic Anion Transporting Polypeptide (OATP) 1B3 is a Significant Transporter for Hepatic Uptake of Conjugated Bile Acids in Humans
Pan Q, Zhu G, Xu Z, Zhu J, Ouyang J, Tong Y, Zhao N, Zhang X, Cheng Y, Zhang L, Tan Y, Li J, Zhang C, Chen W, Cai S, Boyer J, Chai J. Organic Anion Transporting Polypeptide (OATP) 1B3 is a Significant Transporter for Hepatic Uptake of Conjugated Bile Acids in Humans. Cellular And Molecular Gastroenterology And Hepatology 2023, 16: 223-242. PMID: 37146714, PMCID: PMC10394288, DOI: 10.1016/j.jcmgh.2023.04.007.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBile Acids and SaltsCholestasisHumansLiverMiceOrganic Anion TransportersUrsodeoxycholic AcidConceptsBA uptake transportersBile duct ligationHepatic neutrophil infiltrationCholestatic liver injuryProinflammatory cytokine productionCholic acid dietAdaptive protective responseLiver-specific overexpressionWild-type miceConjugated bile acidsUptake transportersPrimary hepatocytesUDCA feedingNeutrophil infiltrationBDL miceLiver injuryCytokine productionBile flowDuct ligationOrganic anion transporting polypeptide (OATP) 1B3Conjugated BAsTransgenic miceHepatic uptakeBile acidsProtective response
2021
Adjunct Fenofibrate Up‐regulates Bile Acid Glucuronidation and Improves Treatment Response For Patients With Cholestasis
Gallucci GM, Trottier J, Hemme C, Assis DN, Boyer JL, Barbier O, Ghonem NS. Adjunct Fenofibrate Up‐regulates Bile Acid Glucuronidation and Improves Treatment Response For Patients With Cholestasis. Hepatology Communications 2021, 5: 2035-2051. PMID: 34558841, PMCID: PMC8631103, DOI: 10.1002/hep4.1787.Peer-Reviewed Original ResearchConceptsSerum bile acidsSerum alkaline phosphataseBile acidsTreatment responseIncomplete responseTotal serum bile acidsElevated serum alkaline phosphatasePeroxisome proliferator-activated receptor alphaProliferator-activated receptor alphaAlkaline phosphatasePrimary sclerosing cholangitisPrimary biliary cholangitisStandard of careSerum ALP levelsBile acid glucuronidationCytotoxic bile acidsPrimary human hepatocytesBA detoxificationFenofibrate therapySclerosing cholangitisAdult patientsBiliary cholangitisLiver failureCombination therapyImproved outcomes
2020
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
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
2017
Combination 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
2010
Combination of retinoic acid and ursodeoxycholic acid attenuates liver injury in bile duct–ligated rats and human hepatic cells
He H, Mennone A, Boyer JL, Cai S. Combination of retinoic acid and ursodeoxycholic acid attenuates liver injury in bile duct–ligated rats and human hepatic cells. Hepatology 2010, 53: 548-557. PMID: 21274875, PMCID: PMC3069505, DOI: 10.1002/hep.24047.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBile Acids and SaltsBile DuctsCell ProliferationCells, CulturedCholestasis, IntrahepaticCholesterol 7-alpha-HydroxylaseCollagen Type ICollagen Type I, alpha 1 ChainDisease Models, AnimalHepatocytesHumansLigationLiverMaleMatrix Metalloproteinase 2RatsRats, Sprague-DawleySmad2 ProteinTretinoinUrsodeoxycholic AcidConceptsBile duct ligationBile salt pool sizeLX-2 cellsUrsodeoxycholic acidHepatic stellate cellsRetinoic acidLiver fibrosisStellate cellsPhosphate-buffered salineCommon bile duct ligationMale Sprague-Dawley ratsPrimary human hepatic stellate cellsTumor necrosis factor αBile duct-ligated ratsHuman hepatic stellate cellsBile duct proliferationHuman hepatocytesLiver hydroxyproline contentNecrosis factor αSprague-Dawley ratsAcute promyelocytic leukemiaΑ-SMA expressionDuct-ligated ratsSmooth muscle actinMatrix metalloproteinase-2
2007
Clinical trial: modulation of human placental multidrug resistance proteins in cholestasis of pregnancy by ursodeoxycholic acid
AZZAROLI F, MENNONE A, FELETTI V, SIMONI P, BAGLIVO E, MONTAGNANI M, RIZZO N, PELUSI G, DE ALOYSIO D, LODATO F, FESTI D, COLECCHIA A, RODA E, BOYER J, MAZZELLA G. Clinical trial: modulation of human placental multidrug resistance proteins in cholestasis of pregnancy by ursodeoxycholic acid. Alimentary Pharmacology & Therapeutics 2007, 26: 1139-1146. PMID: 17894656, DOI: 10.1111/j.1365-2036.2007.03462.x.Peer-Reviewed Original ResearchConceptsUrsodeoxycholic acid administrationBile acid levelsUrsodeoxycholic acidBile acidsAcid administrationIntrahepatic cholestasisCord bloodMaternal serum bile acidsCord blood bilirubinAcid levelsRNA expressionCholestasis of pregnancySerum bile acidsTotal bile acidsMRP3 protein expressionPregnancy patientsPhysiological pregnancyPregnant womenMultidrug resistance proteinBlood bilirubinMRP2 expressionMRP4 expressionCholestasisMultidrug resistancePregnancy
1999
The effect of ursodeoxycholic acid on the florid duct lesion of primary biliary cirrhosis
Combes B, Markin R, Wheeler D, Rubin R, West A, Mills A, Eigenbrodt E, Maddrey W, Munoz S, Garcia‐Tsao G, Bonner G, Boyer J, Luketic V, Shiffman M, Peters M, White H, Zetterman R, Carithers R. The effect of ursodeoxycholic acid on the florid duct lesion of primary biliary cirrhosis. Hepatology 1999, 30: 602-605. PMID: 10462363, PMCID: PMC3935822, DOI: 10.1002/hep.510300315.Peer-Reviewed Original ResearchConceptsFlorid duct lesionsPrimary biliary cirrhosisBile duct destructionDuct lesionsUrsodeoxycholic acidDuct destructionBiliary cirrhosisPlacebo-controlled trialNeedle biopsy specimensUDCA patientsAdvanced diseasePlacebo medicationEarly diseaseBiopsy specimensPatientsLesionsBeneficial effectsPathology literaturePrevalenceCirrhosisPlaceboMedicationsDiseaseYearsHepatopathologistBiliary bile acids in primary biliary cirrhosis: Effect of ursodeoxycholic acid
Combes B, Carithers R, Maddrey W, Munoz S, Garcia‐Tsao G, Bonner G, Boyer J, Luketic V, Shiffman M, Peters M, White H, Zetterman R, Risser R, Rossi S, Hofmann A. Biliary bile acids in primary biliary cirrhosis: Effect of ursodeoxycholic acid. Hepatology 1999, 29: 1649-1654. PMID: 10347103, PMCID: PMC4004074, DOI: 10.1002/hep.510290618.Peer-Reviewed Original ResearchMeSH KeywordsBileBile Acids and SaltsChenodeoxycholic AcidCholic AcidChromatography, GasChromatography, High Pressure LiquidDeoxycholic AcidDouble-Blind MethodDrug Administration ScheduleFemaleHumansLithocholic AcidLiver Cirrhosis, BiliaryMaleMiddle AgedPlacebosRegression AnalysisReproducibility of ResultsTime FactorsUrsodeoxycholic AcidConceptsPrimary biliary cirrhosisBile acid compositionUrsodeoxycholic acidBile acidsBiliary cirrhosisSeverity of PBCSingle bedtime dosePlacebo-controlled trialBiliary bile acidsEndogenous bile acidsMajor bile acidsBedtime dosePlacebo medicationDuodenal bileHigh-pressure liquid chromatography methodPatientsNormal personsBileSignificant decreaseCirrhosisAcid compositionCDCATaurineLiquid chromatography methodYears
1998
Ursodeoxycholic acid in cholestasis: Potential mechanisms of action and therapeutic applications
Beuers U, Boyer J, Paumgartner G. Ursodeoxycholic acid in cholestasis: Potential mechanisms of action and therapeutic applications. Hepatology 1998, 28: 1449-1453. PMID: 9828205, DOI: 10.1002/hep.510280601.Peer-Reviewed Original Research
1997
Bile acid concentrations in human and rat liver tissue and in hepatocyte nuclei
Setchell K, Rodrigues C, Clerici C, Solinas A, Morelli A, Gartung C, Boyer J. Bile acid concentrations in human and rat liver tissue and in hepatocyte nuclei. Gastroenterology 1997, 112: 226-235. PMID: 8978363, DOI: 10.1016/s0016-5085(97)70239-7.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsBile Acids and SaltsCell NucleusCholestasisHumansLiverMaleMiddle AgedRatsRats, Sprague-DawleyTaurochenodeoxycholic AcidUrsodeoxycholic AcidConceptsBile acid concentrationsBile acid administrationBile duct ligationBile acid poolLiver tissueBile acidsAcid administrationRat liver tissueDuct ligationTotal bile acid concentrationTissue concentrationsBile acid compositionSham-operated ratsLiver tissue levelsMajor bile acidsHydrophobic bile acidsHepatocyte nucleiAcid poolHuman liver tissueExperimental cholestasisAbstractTextTissue levelsRat hepatic nucleiAcid concentrationAdministration
1995
A randomized, double‐blind, placebo‐controlled trial of ursodeoxycholic acid in primary biliary cirrhosis
Combes B, Carithers R, Maddrey W, Lin D, McDonald M, Wheeler D, Eigenbrodt E, Muñoz S, Rubin R, Garcia‐Tsao G, Bonner G, West A, Boyer J, Luketic V, Shiffman M, Mills A, Peters M, White H, Zetterman R, Rossi S, Hofmann A, Markin R. A randomized, double‐blind, placebo‐controlled trial of ursodeoxycholic acid in primary biliary cirrhosis. Hepatology 1995, 22: 759-766. PMID: 7657280, DOI: 10.1002/hep.1840220311.Peer-Reviewed Original ResearchMeSH KeywordsAdultBileBilirubinDouble-Blind MethodFemaleHumansLiverLiver Cirrhosis, BiliaryMaleMiddle AgedPlacebosTime FactorsTreatment FailureUrsodeoxycholic AcidConceptsPrimary biliary cirrhosisSerum bilirubinBiliary cirrhosisStratum 1Advanced primary biliary cirrhosisPlacebo-controlled trialBile acid poolLiver histologyPrognostic factorsTreatment failureSingle doseUrsodeoxycholic acidSevere symptomsPatientsUrsodiolLaboratory testsPlaceboHistologyBilirubinCirrhosisBiochemical testsGood responseStratum 3Acid poolLess effect
1993
Effect of ursodeoxycholic acid on intracellular pH regulation in isolated rat bile duct epithelial cells
Alvaro D, Mennone A, Boyer J. Effect of ursodeoxycholic acid on intracellular pH regulation in isolated rat bile duct epithelial cells. American Journal Of Physiology 1993, 265: g783-g791. PMID: 8238362, DOI: 10.1152/ajpgi.1993.265.4.g783.Peer-Reviewed Original ResearchConceptsBile duct epithelial cellsUrsodeoxycholic acidDuct epithelial cellsBDE cellsHCO3- excretionEffect of UDCAEpithelial cellsHCO3- exchangeCholic acidKrebs-Ringer bicarbonateUDCA infusionUDCA withdrawalRat bile duct epithelial cellsKRB mediumHCO3- symportNormal rat liverIntracellular pH regulationHCO3- secretionSodium tauroursodeoxycholateSecondary activationBasal levelsPresence of HCO3TauroursodeoxycholateRat liverHypercholeresis
1991
Effect of UDCA on intracellular and biliary pH in isolated rat hepatocyte couplets and perfused livers
Strazzabosco M, Sakisaka S, Hayakawa T, Boyer J. Effect of UDCA on intracellular and biliary pH in isolated rat hepatocyte couplets and perfused livers. American Journal Of Physiology 1991, 260: g58-g69. PMID: 1987808, DOI: 10.1152/ajpgi.1991.260.1.g58.Peer-Reviewed Original ResearchConceptsBiliary HCO3- concentrationUrsodeoxycholic acidRat hepatocyte coupletsBiliary pHAcid loadEffect of UDCABile duct lumenHepatocyte coupletsIsolated rat hepatocyte coupletsBiliary epitheliumHCO3- concentrationDuct lumenRemoval of ClHCO3- exchangeRat liverLiverIPRLHepatocytesHypercholeresisPerfusateBileExcretionEpitheliumAmiloride
1989
Quantitative assessment of canalicular bile formation in isolated hepatocyte couplets using microscopic optical planimetry.
Gautam A, Ng O, Strazzabosco M, Boyer J. Quantitative assessment of canalicular bile formation in isolated hepatocyte couplets using microscopic optical planimetry. Journal Of Clinical Investigation 1989, 83: 565-573. PMID: 2913052, PMCID: PMC303716, DOI: 10.1172/jci113919.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBileBile CanaliculiBile Ducts, IntrahepaticLiverMicroscopy, ElectronRatsRats, Inbred StrainsTaurocholic AcidUrsodeoxycholic AcidConceptsIsolated rat hepatocyte couplets
1987
Ursodeoxycholate stimulates Na+-H+ exchange in rat liver basolateral plasma membrane vesicles.
Moseley R, Ballatori N, Smith D, Boyer J. Ursodeoxycholate stimulates Na+-H+ exchange in rat liver basolateral plasma membrane vesicles. Journal Of Clinical Investigation 1987, 80: 684-690. PMID: 3040805, PMCID: PMC442291, DOI: 10.1172/jci113122.Peer-Reviewed Original Research