2023
Cell-matrix interactions control biliary organoid polarity, architecture, and differentiation
Fiorotto R, Mariotti V, Taleb S, Zehra S, Nguyen M, Amenduni M, Strazzabosco M. Cell-matrix interactions control biliary organoid polarity, architecture, and differentiation. Hepatology Communications 2023, 7: e0094. PMID: 36972396, PMCID: PMC10503667, DOI: 10.1097/hc9.0000000000000094.Peer-Reviewed Original ResearchConceptsBiliary organoidsNovel organoid modelImmune cell typesOrganotypic culture systemProinflammatory chemokinesStem cell featuresBiliary epitheliumExtracellular matrixEpithelial permeabilityImportant causeBile acidsBiliary differentiationBile transportHuman liverOrganoid modelsDisease modelsCholangiopathyCell featuresTight junctionsLiverCell typesInternal lumenOrganoidsSingle-cell transcriptomicsPathogenic bacteria
2022
Bile acids and their receptors: modulators and therapeutic targets in liver inflammation
Bertolini A, Fiorotto R, Strazzabosco M. Bile acids and their receptors: modulators and therapeutic targets in liver inflammation. Seminars In Immunopathology 2022, 44: 547-564. PMID: 35415765, PMCID: PMC9256560, DOI: 10.1007/s00281-022-00935-7.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsBile acidsLiver diseaseTherapeutic targetAutoimmune liver diseaseCholestatic liver diseaseBile acid receptorAbsorption of lipidsFat-soluble vitaminsLiver inflammationInflammatory diseasesImmunomodulatory propertiesAcid receptorsInflammationDiseaseReceptorsClinical applicationLiverNutrient metabolismPathway
2021
Improved performance and consistency of deep learning 3D liver segmentation with heterogeneous cancer stages in magnetic resonance imaging
Gross M, Spektor M, Jaffe A, Kucukkaya AS, Iseke S, Haider SP, Strazzabosco M, Chapiro J, Onofrey JA. Improved performance and consistency of deep learning 3D liver segmentation with heterogeneous cancer stages in magnetic resonance imaging. PLOS ONE 2021, 16: e0260630. PMID: 34852007, PMCID: PMC8635384, DOI: 10.1371/journal.pone.0260630.Peer-Reviewed Original ResearchThe Neglected Role of Bile Duct Epithelial Cells in NASH
Cadamuro M, Lasagni A, Sarcognato S, Guido M, Fabris R, Strazzabosco M, Strain AJ, Simioni P, Villa E, Fabris L. The Neglected Role of Bile Duct Epithelial Cells in NASH. Seminars In Liver Disease 2021, 42: 034-047. PMID: 34794182, DOI: 10.1055/s-0041-1739455.Peer-Reviewed Original ResearchConceptsNonalcoholic fatty liver diseaseNonalcoholic steatohepatitisLiver diseaseInsulin resistancePrevalent liver diseaseBile duct epithelial cellsFatty liver diseaseSubset of patientsCommon pathogenetic mechanismDuct epithelial cellsMultiple biological effectsFibro-inflammationHepatic manifestationNAFLD patientsPortal fibrosisMetabolic syndromeBile ductDuctular reactionDisease progressionPathogenetic mechanismsLiver cancerMetabolic alterationsProgenitor cell compartmentEpithelial cellsDisease
2020
Abnormal Liver Function Tests in Patients With COVID‐19: Relevance and Potential Pathogenesis
Bertolini A, van de Peppel I, Bodewes FAJA, Moshage H, Fantin A, Farinati F, Fiorotto R, Jonker JW, Strazzabosco M, Verkade HJ, Peserico G. Abnormal Liver Function Tests in Patients With COVID‐19: Relevance and Potential Pathogenesis. Hepatology 2020, 72: 1864-1872. PMID: 32702162, PMCID: PMC7404414, DOI: 10.1002/hep.31480.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAbnormal liver function testsLiver function testsCOVID-19 patientsAspartate aminotransferaseFunction testsHospitalized coronavirus disease 2019 (COVID-19) patientsSevere COVID-19 diseaseCoronavirus disease 2019 (COVID-19) patientsElevated liver function testsPre-existing liver diseaseDrug-induced liver injuryCOVID-19Hyper-inflammatory statusAlanine aminotransferase levelsLopinavir/ritonavirOvert liver failureStart of treatmentUse of acetaminophenCause of deathPlasma aspartate aminotransferaseUpper reference limitSARS-CoV-2COVID-19 diseaseAlkaline phosphataseALT elevationLiver Matrix in Benign and Malignant Biliary Tract Disease
Fabris L, Cadamuro M, Cagnin S, Strazzabosco M, Gores G. Liver Matrix in Benign and Malignant Biliary Tract Disease. Seminars In Liver Disease 2020, 40: 282-297. PMID: 32162285, DOI: 10.1055/s-0040-1705109.Peer-Reviewed Original ResearchConceptsMalignant biliary tract diseasesBiliary tract diseaseExtracellular matrixReactive ductular cellsPro-oncogenic effectsHepatic progenitor cellsExtracellular matrix undergoesBiliary repairDuctular reactionTract diseaseBiliary damageMalignant transformationResident cellsDuctular cellsMain molecular factorsProgenitor cellsMolecular factorsMechanical signalsLiver matrixNoncollagenous glycoproteinsStructural alterationsDirect interactionBiochemical compositionCellsMultifunctional molecules
2019
The challenges of primary biliary cholangitis: What is new and what needs to be done
Terziroli Beretta-Piccoli B, Mieli-Vergani G, Vergani D, Vierling JM, Adams D, Alpini G, Banales JM, Beuers U, Björnsson E, Bowlus C, Carbone M, Chazouillères O, Dalekos G, De Gottardi A, Harada K, Hirschfield G, Invernizzi P, Jones D, Krawitt E, Lanzavecchia A, Lian ZX, Ma X, Manns M, Mavilio D, Quigley EM, Sallusto F, Shimoda S, Strazzabosco M, Swain M, Tanaka A, Trauner M, Tsuneyama K, Zigmond E, Gershwin ME. The challenges of primary biliary cholangitis: What is new and what needs to be done. Journal Of Autoimmunity 2019, 105: 102328. PMID: 31548157, DOI: 10.1016/j.jaut.2019.102328.Peer-Reviewed Original ResearchConceptsPrimary biliary cholangitisAnti-mitochondrial autoantibodiesBiochemical cholestasisBiliary cholangitisBiliary epitheliumUrsodeoxycholic acidPBC-specific anti-nuclear antibodiesBile acidsToxic hydrophobic bile acidsAutoimmune liver diseaseSecond-line treatmentFirst-line treatmentAnti-nuclear antibodiesReliable disease markersEarly disease stagesCholestatic biochemical profileNew therapeutic approachesHydrophobic bile acidsAutoimmune originSeronegative casesLiver histologyAutoimmune attackFemale preponderanceHistologic confirmationImmunologic pathwaysDiagnostic Value of Quantitative Perfusion Computed Tomography Technique in the Assessment of Tumor Response to Sorafenib in Patients With Advanced Hepatocellular Carcinoma
Ippolito D, Querques G, Pecorelli A, Franzesi C, Okolicsanyi S, Strazzabosco M, Sironi S. Diagnostic Value of Quantitative Perfusion Computed Tomography Technique in the Assessment of Tumor Response to Sorafenib in Patients With Advanced Hepatocellular Carcinoma. Journal Of Computer Assisted Tomography 2019, Publish Ahead of Print: &na;. PMID: 30407241, DOI: 10.1097/rct.0000000000000807.Peer-Reviewed Original ResearchConceptsAdvanced hepatocellular carcinomaHepatocellular carcinomaProgressive diseasePartial responseDynamic contrast-enhanced perfusionPerfusion CT valuesHepatic perfusion indexResponse Evaluation CriteriaMultifocal hepatocellular carcinomaIntravenous bolus injectionBlood flow changesContrast-enhanced perfusionRow Computed TomographyPerfusion CT techniquesStandard of referenceNonprogressor groupProgressor groupSorafenib administrationCirrhotic patientsArterial perfusionHepatic perfusionPD patientsTumor responsePerfusion indexTherapeutic response
2018
Platelet-derived growth factor-D enables liver myofibroblasts to promote tumor lymphangiogenesis in cholangiocarcinoma
Cadamuro M, Brivio S, Mertens J, Vismara M, Moncsek A, Milani C, Fingas C, Cristina Malerba M, Nardo G, Dall'Olmo L, Milani E, Mariotti V, Stecca T, Massani M, Spirli C, Fiorotto R, Indraccolo S, Strazzabosco M, Fabris L. Platelet-derived growth factor-D enables liver myofibroblasts to promote tumor lymphangiogenesis in cholangiocarcinoma. Journal Of Hepatology 2018, 70: 700-709. PMID: 30553841, PMCID: PMC10878126, DOI: 10.1016/j.jhep.2018.12.004.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBile Duct NeoplasmsCancer-Associated FibroblastsCell Line, TumorCholangiocarcinomaDisease Models, AnimalEndothelial CellsHeterograftsHumansImatinib MesylateLiverLymphangiogenesisLymphokinesMaleMiceMice, SCIDMyofibroblastsPlatelet-Derived Growth FactorProtein Kinase InhibitorsRatsRats, Inbred F344Receptor, Platelet-Derived Growth Factor betaVascular Endothelial Growth Factor AVascular Endothelial Growth Factor CConceptsCancer-associated fibroblastsLymphatic endothelial cellsCholangiocarcinoma specimensMetastatic spreadStromal reactionLiver myofibroblastsGrowth factorExtensive stromal reactionLymph node metastasisEarly metastatic spreadLevels of VEGFBH3 mimetic navitoclaxPlatelet-derived growth factorRole of PDGFVascular growth factorsTumor-associated lymphangiogenesisVEGF-C secretionTransendothelial electric resistanceCholangiocarcinoma invasivenessHuman lymphatic endothelial cellsCurative therapyNode metastasisBiliary treeEarly metastasisPDGFRβ inhibitorFibroinflammatory Liver Injuries as Preneoplastic Condition in Cholangiopathies
Cannito S, Milani C, Cappon A, Parola M, Strazzabosco M, Cadamuro M. Fibroinflammatory Liver Injuries as Preneoplastic Condition in Cholangiopathies. International Journal Of Molecular Sciences 2018, 19: 3875. PMID: 30518128, PMCID: PMC6321547, DOI: 10.3390/ijms19123875.Peer-Reviewed Original ResearchConceptsMain molecular mechanismsDifferent lineagesPrimary sclerosing cholangitisMolecular mechanismsProfibrotic chemokinesNeoplastic transformationSclerosing cholangitisCaroli's diseaseOrgan dysfunctionChronic cholangiopathiesInflammatory infiltrateLiver injuryPeriportal fibrosisLiver diseaseInflammatory cellsProinflammatory cytokinesBiliary treePreneoplastic conditionsDifferent etiologiesTumor developmentMurine modelLiver responseParacrine fashionHepatic responseCellular typesDynamic contrast enhanced perfusion CT imaging: A diagnostic biomarker tool for survival prediction of tumour response to antiangiogenetic treatment in patients with advanced HCC lesions
Ippolito D, Querques G, Okolicsanyi S, Franzesi C, Pecorelli A, Lombardi S, Orsini E, Strazzabosco M, Sironi S. Dynamic contrast enhanced perfusion CT imaging: A diagnostic biomarker tool for survival prediction of tumour response to antiangiogenetic treatment in patients with advanced HCC lesions. European Journal Of Radiology 2018, 106: 62-68. PMID: 30150052, DOI: 10.1016/j.ejrad.2018.07.012.Peer-Reviewed Original ResearchConceptsAdvanced hepatocellular carcinomaAnti-angiogenic therapyPerfusion CT imagingHepatocellular carcinomaPerfusion parametersProgressor groupSurvival rateNon-progressor groupOverall survival rateKaplan-Meier analysisAssessment of responseAntiangiogenetic treatmentCirrhotic patientsSorafenib administrationPrognostic indicatorTumor responseTarget lesionsHCC lesionsIndividualized treatmentTumor neoangiogenesisPatientsOverall populationHigher survival rateCT imagingSurvival predictionβ‐Catenin and interleukin‐1β–dependent chemokine (C‐X‐C motif) ligand 10 production drives progression of disease in a mouse model of congenital hepatic fibrosis
Kaffe E, Fiorotto R, Pellegrino F, Mariotti V, Amenduni M, Cadamuro M, Fabris L, Strazzabosco M, Spirli C. β‐Catenin and interleukin‐1β–dependent chemokine (C‐X‐C motif) ligand 10 production drives progression of disease in a mouse model of congenital hepatic fibrosis. Hepatology 2018, 67: 1903-1919. PMID: 29140564, PMCID: PMC5906178, DOI: 10.1002/hep.29652.Peer-Reviewed Original ResearchConceptsSignal transducerΒ-cateninJanus kinase/signal transducerKinase/signal transducerActivator of transcriptionProtein kinase ATranscription 3 (STAT3) phosphorylationHepatic disease 1 (PKHD1) geneNOD-like receptorsKinase ATranscription 3Novel therapeutic avenuesGenetic diseasesNuclear translocationCognate receptorsFamily 3Nuclear factorMouse modelPKHD1Activated B cellsPhosphorylationActivatorCyst growthTherapeutic avenuesAMG 487
2017
Pathophysiologic implications of innate immunity and autoinflammation in the biliary epithelium
Strazzabosco M, Fiorotto R, Cadamuro M, Spirli C, Mariotti V, Kaffe E, Scirpo R, Fabris L. Pathophysiologic implications of innate immunity and autoinflammation in the biliary epithelium. Biochimica Et Biophysica Acta (BBA) - Molecular Basis Of Disease 2017, 1864: 1374-1379. PMID: 28754453, PMCID: PMC5785585, DOI: 10.1016/j.bbadis.2017.07.023.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsToll-like receptorsLiver damageCystic fibrosis-related liver diseaseInnate immunityDamage-associated molecular patternsEpithelial innate immunityPro-inflammatory behaviorBiliary epithelial cellsNumber of receptorsJesus BanalesMarco MarzioniNicholas LaRussoPeter JansenLiver injuryLiver diseaseBile flowInflammatory processBiliary epitheliumInflammatory responsePathophysiologic implicationsReparative processesNumber of evidencesFirst defense lineCholangiocytesMolecular patternsAnimal models of biliary injury and altered bile acid metabolism
Mariotti V, Strazzabosco M, Fabris L, Calvisi DF. Animal models of biliary injury and altered bile acid metabolism. Biochimica Et Biophysica Acta (BBA) - Molecular Basis Of Disease 2017, 1864: 1254-1261. PMID: 28709963, PMCID: PMC5764833, DOI: 10.1016/j.bbadis.2017.06.027.Peer-Reviewed Original ResearchConceptsBile acid metabolismBiliary injuryMouse modelAnimal modelsDistinct immune systemCholestatic liver injuryAcid metabolismJesus BanalesMarco MarzioniNicholas LaRussoPeter JansenBiliary repairLiver injuryDuctular reactionLiver repairObstructive cholestasisDisease progressionPeribiliary inflammationMain phenotypic featuresBiliary dysgenesisViral infectionImmune systemLiver homeostasisLiver phenotypeHuman settingEmerging concepts in biliary repair and fibrosis
Fabris L, Spirli C, Cadamuro M, Fiorotto R, Strazzabosco M. Emerging concepts in biliary repair and fibrosis. AJP Gastrointestinal And Liver Physiology 2017, 313: g102-g116. PMID: 28526690, PMCID: PMC5582882, DOI: 10.1152/ajpgi.00452.2016.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsReactive ductular cellsBiliary repairBiliary treeDuctular cellsProliferation of cholangiocytesCongenital hepatic fibrosisBiliary fibrosisInflammatory changesBiliary atresiaChronic cholangiopathiesClinical progressionClinical hepatologyHepatic fibrosisLiver repairMajor unmetBiliary epitheliumChronic diseasesChronic damageReparative responseAlagille syndromeLiver pathophysiologyReparative processesFibrosisPathological repairCellular elements
2015
Emerging roles of Notch signaling in liver disease
Geisler F, Strazzabosco M. Emerging roles of Notch signaling in liver disease. Hepatology 2015, 61: 382-392. PMID: 24930574, PMCID: PMC4268103, DOI: 10.1002/hep.27268.Peer-Reviewed Original ResearchConceptsRole of NotchNotch signalingMammalian cell fateSpecific cellular contextCell fateCellular contextOrgan homeostasisStem cell featuresSignificance of NotchDistinct liver cell typesLiver developmentLiver cell typesCell typesLiver diseaseIntrahepatic cholangiocarcinomaLiver malignanciesHepatocellular carcinomaFurther cellHomeostasisLiver homeostasisLiver metabolismPersistent activationClinical practiceRepair processSignaling
2013
Notch signaling and new therapeutic options in liver disease
Morell CM, Strazzabosco M. Notch signaling and new therapeutic options in liver disease. Journal Of Hepatology 2013, 60: 885-890. PMID: 24308992, DOI: 10.1016/j.jhep.2013.11.028.Peer-Reviewed Original ResearchConceptsLiver diseaseTherapeutic agentsNew therapeutic optionsNotch signalingSpecific therapeutic agentsStem cell featuresTherapeutic optionsLiver malignanciesLiver metabolismTherapeutic relevanceAberrant activationLiver regenerationPersistent activationDiseaseAdult liverPossible targetsFurther studiesCell featuresNovel findingsRecent reportsNotch pathwayLiverCritical playersSignalingActivationVascular biology of the biliary epithelium
Morell CM, Fabris L, Strazzabosco M. Vascular biology of the biliary epithelium. Journal Of Gastroenterology And Hepatology 2013, 28: 26-32. PMID: 23855292, PMCID: PMC3721432, DOI: 10.1111/jgh.12022.Peer-Reviewed Original ResearchMeSH KeywordsAngiopoietinsAnimalsAutocrine CommunicationBile Duct DiseasesBile Ducts, IntrahepaticEpithelial CellsEpitheliumHumansLiverLiver Diseases, AlcoholicLiver RegenerationNeovascularization, PathologicParacrine CommunicationPlatelet-Derived Growth FactorRatsSignal TransductionVascular Endothelial Growth Factor AConceptsBile ductIntrahepatic bile ductsHepatic arteryPeribiliary plexusUnderlying molecular mechanismsArterial supplyLiver repairNormal organ physiologyLiver pathophysiologyVascular cell typesPathophysiological settingsVascular structuresStrong associationVascular biologyDifferent vascular cell typesCholangiocytesAngiogenic signalsLiver developmentCell typesMolecular mechanismsOrgan physiologyDuctAssociationCross talkNotch signalling beyond liver development: Emerging concepts in liver repair and oncogenesis
Morell CM, Fiorotto R, Fabris L, Strazzabosco M. Notch signalling beyond liver development: Emerging concepts in liver repair and oncogenesis. Clinics And Research In Hepatology And Gastroenterology 2013, 37: 447-454. PMID: 23806629, DOI: 10.1016/j.clinre.2013.05.008.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAnimalsBile Duct NeoplasmsBiliary TractCalcium-Binding ProteinsCarcinogenesisCarcinoma, HepatocellularCholangiocarcinomaHepatocytesHumansIntercellular Signaling Peptides and ProteinsJagged-1 ProteinLiverLiver NeoplasmsLiver RegenerationMembrane ProteinsReceptor Cross-TalkReceptors, NotchSerrate-Jagged ProteinsSignal TransductionEASL Recognition Awardee 2013 Professor Jesus Prieto
Strazzabosco M. EASL Recognition Awardee 2013 Professor Jesus Prieto. Journal Of Hepatology 2013, 59: 408-410. PMID: 23764136, DOI: 10.1016/j.jhep.2013.05.012.Peer-Reviewed Original Research