2023
Advancing diagnosis and management of liver disease in adults through exome sequencing
Zheng M, Hakim A, Konkwo C, Deaton A, Ward L, Genetics A, Silveira M, Assis D, Liapakis A, Jaffe A, Jiang Z, Curry M, Lai M, Cho M, Dykas D, Bale A, Mistry P, Vilarinho S. Advancing diagnosis and management of liver disease in adults through exome sequencing. EBioMedicine 2023, 95: 104747. PMID: 37566928, PMCID: PMC10433007, DOI: 10.1016/j.ebiom.2023.104747.Peer-Reviewed Original ResearchConceptsLiver diseaseWhole-exome sequencingUnknown etiologyTertiary referral academic medical centerReferral academic medical centerExome sequencingLiver disease patientsManagement of adultsAcademic health care centerComprehensive clinical evaluationHealth care centersAcademic medical centerGenetic variantsRare genetic variantsAdult patientsLiver centersHepatic steatosisDisease patientsClinical evaluationCare centerFamily historyMedical CenterClinical valueAdult medicinePatientsResearch gaps and opportunities in autoimmune hepatitis—Results of the international autoimmune hepatitis group research workshop 2022
Snijders R, Assis D, Oo Y, Sebode M, Taubert R, Willemse J, Tomsin B, Lohse A, Drenth J, Gevers T, Diseases T. Research gaps and opportunities in autoimmune hepatitis—Results of the international autoimmune hepatitis group research workshop 2022. Liver International 2023, 43: 1375-1384. PMID: 37035872, DOI: 10.1111/liv.15573.Peer-Reviewed Original ResearchConceptsInternational Autoimmune Hepatitis GroupAutoimmune hepatitisRare autoimmune liver diseaseMajor unmet clinical needClinical needAdult autoimmune hepatitisAutoimmune Hepatitis GroupAutoimmune liver diseaseLiver-related complicationsHealth-related qualityNew immunomodulatory therapiesInflammatory immune reactionsUnmet clinical needClinical trial designSpecific diagnostic testsQuality of lifeHepatitis groupNonselective immunosuppressionImmunomodulatory therapyLiver diseasePrognostic markerImmune reactionsPatient representativesTrial designCare deliveryOutcomes 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 patients
2021
Outcome of COVID‐19 in Patients With Autoimmune Hepatitis: An International Multicenter Study
Efe C, Dhanasekaran R, Lammert C, Ebik B, la Tijera F, Aloman C, Calışkan A, Peralta M, Gerussi A, Massoumi H, Catana AM, Torgutalp M, Purnak T, Rigamonti C, Aldana A, Khakoo N, Kacmaz H, Nazal L, Frager S, Demir N, Irak K, Ellik ZM, Balaban Y, Atay K, Eren F, Cristoferi L, Batıbay E, Urzua Á, Snijders R, Kıyıcı M, Akyıldız M, Ekin N, Carr RM, Harputluoğlu M, Hatemi I, Mendizabal M, Silva M, Idilman R, Silveira M, Drenth JPH, Assis DN, Björnsson E, Boyer JL, Invernizzi P, Levy C, Schiano TD, Ridruejo E, Wahlin S. Outcome of COVID‐19 in Patients With Autoimmune Hepatitis: An International Multicenter Study. Hepatology 2021, 73: 2099-2109. PMID: 33713486, PMCID: PMC8250536, DOI: 10.1002/hep.31797.Peer-Reviewed Original ResearchConceptsSevere COVID-19Chronic liver diseaseAutoimmune hepatitisLiver injuryMulticenter studyCOVID-19Causes of CLDPropensity score-matched cohortSevere COVID-19 outcomesContinuation of immunosuppressionMaintenance of immunosuppressionOutcomes of patientsIntensive care admissionUse of antiviralsInternational multicenter studyCOVID-19 outcomesCOVID-19 diagnosisContinued immunosuppressionCare admissionCause mortalityIndependent predictorsMedian ageLiver diseaseMechanical ventilationRetrospective study
2020
Diagnosis and Management of Autoimmune Hepatitis in Adults and Children: 2019 Practice Guidance and Guidelines From the American Association for the Study of Liver Diseases
Mack CL, Adams D, Assis DN, Kerkar N, Manns MP, Mayo MJ, Vierling JM, Alsawas M, Murad MH, Czaja AJ. Diagnosis and Management of Autoimmune Hepatitis in Adults and Children: 2019 Practice Guidance and Guidelines From the American Association for the Study of Liver Diseases. Hepatology 2020, 72: 671-722. PMID: 31863477, DOI: 10.1002/hep.31065.Peer-Reviewed Original ResearchFenofibrate 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 α4β7Clinical utility of genomic analysis in adults with idiopathic liver disease
Hakim A, Zhang X, DeLisle A, Oral EA, Dykas D, Drzewiecki K, Assis DN, Silveira M, Batisti J, Jain D, Bale A, Mistry PK, Vilarinho S. Clinical utility of genomic analysis in adults with idiopathic liver disease. Journal Of Hepatology 2019, 70: 1214-1221. PMID: 31000363, PMCID: PMC6526061, DOI: 10.1016/j.jhep.2019.01.036.Peer-Reviewed Original ResearchConceptsIdiopathic liver diseaseUnexplained liver diseaseManagement of adultsWhole-exome sequencingLiver diseaseAdult patientsUnknown etiologyHeterozygous variantsUse of WESAmelioration of dyslipidemiaDaily insulin requirementLeptin replacement therapyUtility of WESChronic liver diseaseNon-alcoholic steatohepatitisAcademic health care centerHealth care centersHomozygous pathogenic variantUnrelated adult patientsNon-oncological diseasesDisease preventive measuresInsulin requirementsLean patientsDevastating complicationLiver aminotransferases
2018
Histologic features of autoimmune hepatitis: a critical appraisal
Gurung A, Assis DN, McCarty TR, Mitchell KA, Boyer JL, Jain D. Histologic features of autoimmune hepatitis: a critical appraisal. Human Pathology 2018, 82: 51-60. PMID: 30041025, DOI: 10.1016/j.humpath.2018.07.014.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedBiopsyChildChild, PreschoolDatabases, FactualEmperipolesisFemaleHepatitis C, ChronicHepatitis, AutoimmuneHepatocytesHumansKupffer CellsLiverLiver CirrhosisLymphocytesMaleMiddle AgedPlasma CellsPredictive Value of TestsReproducibility of ResultsRetrospective StudiesSeverity of Illness IndexYoung AdultConceptsProminent plasma cellsAutoimmune hepatitisHistologic featuresPlasma cellsInflammatory gradePortal tractsScoring systemInitiation of therapySeverity of hepatitisDifferent control groupsChronic hepatitisHepatitis CFibrosis stageStudy groupDisease processHepatitisControl groupHyaline globulesFurther studiesPatientsTractCritical appraisalCellsGradeTypical features
2017
Primary Sclerosing Cholangitis Is Not Rare Among Blacks in a Multicenter North American Consortium
Goldberg DS, Levy C, Yimam K, Gordon SC, Forman L, Verna E, Yu L, Rahimi R, Schwarz K, Eksteen B, Pratt D, Boyer JL, Assis D, Bowlus C. Primary Sclerosing Cholangitis Is Not Rare Among Blacks in a Multicenter North American Consortium. Clinical Gastroenterology And Hepatology 2017, 16: 591-593. PMID: 29102704, PMCID: PMC5860952, DOI: 10.1016/j.cgh.2017.10.028.Peer-Reviewed Original ResearchCombination 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
2016
A Macrophage Migration Inhibitory Factor Polymorphism Is Associated with Autoimmune Hepatitis Severity in US and Japanese Patients
Assis DN, Takahashi H, Leng L, Zeniya M, Boyer JL, Bucala R. A Macrophage Migration Inhibitory Factor Polymorphism Is Associated with Autoimmune Hepatitis Severity in US and Japanese Patients. Digestive Diseases And Sciences 2016, 61: 3506-3512. PMID: 27696094, PMCID: PMC5106299, DOI: 10.1007/s10620-016-4322-z.Peer-Reviewed Original ResearchMeSH KeywordsAdrenal Cortex HormonesAdultAlanine TransaminaseAntigens, Differentiation, B-LymphocyteAsian PeopleCase-Control StudiesEnzyme-Linked Immunosorbent AssayFemaleGenetic Predisposition to DiseaseHepatitis, AutoimmuneHistocompatibility Antigens Class IIHumansIntramolecular OxidoreductasesJapanMacrophage Migration-Inhibitory FactorsMaleMiddle AgedPolymorphism, GeneticPolymorphism, Single NucleotideSeverity of Illness IndexUnited StatesConceptsMacrophage migration inhibitory factorAIH patientsAutoimmune hepatitisSteroid requirementsMIF expressionMacrophage Migration Inhibitory Factor PolymorphismGC/CC genotypesCC/GCJapanese AIH patientsJapanese patient groupMigration inhibitory factorMultiple autoimmune diseasesGC single nucleotide polymorphismsGC/CCAIH groupHepatitis severityMIF promoterSteroid resistanceMIF genotypeSerum ALTSymptomatic presentationGG patientsHigher ALTClinical parametersMIF polymorphismsThe clinical significance of the MIF homolog d-dopachrome tautomerase (MIF-2) and its circulating receptor (sCD74) in burn
Kim BS, Stoppe C, Grieb G, Leng L, Sauler M, Assis D, Simons D, Boecker AH, Schulte W, Piecychna M, Hager S, Bernhagen J, Pallua N, Bucala R. The clinical significance of the MIF homolog d-dopachrome tautomerase (MIF-2) and its circulating receptor (sCD74) in burn. Burns 2016, 42: 1265-1276. PMID: 27209369, PMCID: PMC5010466, DOI: 10.1016/j.burns.2016.02.005.Peer-Reviewed Original ResearchConceptsTotal body surface areaMacrophage migration inhibitory factorSerum levelsClinical significanceCytokine macrophage migration inhibitory factorEarly post-burn periodPrediction of sepsisBody surface areaMigration inhibitory factorPost-burn periodBurn severity indexDopachrome tautomeraseClinical outcomesBurn patientsReceptor CD74Healthy controlsBurn injuryEarly predictorMember DPatientsPotential biomarkersCD74Inhibitory factorSoluble CD74Severity IndexThe interpretation of hepatic venous pressure gradient tracings – excellent interobserver agreement unrelated to experience
Tandon P, Ripoll C, Assis D, Wongcharatrawee S, Groszmann RJ, Garcia-Tsao G. The interpretation of hepatic venous pressure gradient tracings – excellent interobserver agreement unrelated to experience. Liver International 2016, 36: 1160-1166. PMID: 26763558, DOI: 10.1111/liv.13065.Peer-Reviewed Original ResearchConceptsHepatic venous pressure gradientIntraclass correlation coefficientPortal hypertensionBaseline hepatic venous pressure gradientObserver readingsInterobserver agreementVenous pressure gradientTherapy of patientsBland-Altman plotsPearson's linear regressionSingle centerBland-Altman techniqueCirrhosisLogistic regressionMean differencePatientsHypertensionMmHgExperienced observersResearch settingsPredictorsFurther supportSignificant linear relationshipLinear regressionHepatologists
2013
The role of macrophage migration inhibitory factor in autoimmune liver disease
Assis DN, Leng L, Du X, Zhang CK, Grieb G, Merk M, Garcia AB, McCrann C, Chapiro J, Meinhardt A, Mizue Y, Nikolic‐Paterson D, Bernhagen J, Kaplan MM, Zhao H, Boyer JL, Bucala R. The role of macrophage migration inhibitory factor in autoimmune liver disease. Hepatology 2013, 59: 580-591. PMID: 23913513, PMCID: PMC3877200, DOI: 10.1002/hep.26664.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntigens, Differentiation, B-LymphocyteBiomarkersBiopsyCase-Control StudiesCohort StudiesFemaleGene FrequencyHepatitis, AutoimmuneHistocompatibility Antigens Class IIHumansIntramolecular OxidoreductasesLiverLiver Cirrhosis, BiliaryMacrophage Migration-Inhibitory FactorsMaleMicrosatellite RepeatsMiddle AgedPhenotypePolymorphism, Single NucleotideConceptsMacrophage migration inhibitory factorPrimary biliary cirrhosisAutoimmune hepatitisMigration inhibitory factorMIF receptorHealthy controlsInhibitory factorAutoimmune liver diseaseMIF promoter polymorphismsHepatic stellate cellsEnzyme-linked immunosorbentCATT7 alleleImmunopathogenic basisMIF expressionMIF locusBiliary cirrhosisLiver diseaseInflammatory phenotypeReceptor profileStellate cellsPromoter polymorphismPatientsSerum samplesCD74Single nucleotide polymorphisms