Featured Publications
The Sympathetic Nervous System Promotes Hepatic Lymphangiogenesis, which Is Protective Against Liver Fibrosis
Tanaka M, Jeong J, Thomas C, Zhang X, Zhang P, Saruwatari J, Kondo R, McConnell M, Utsumi T, Iwakiri Y. The Sympathetic Nervous System Promotes Hepatic Lymphangiogenesis, which Is Protective Against Liver Fibrosis. American Journal Of Pathology 2023, 193: 2182-2202. PMID: 37673329, PMCID: PMC10699132, DOI: 10.1016/j.ajpath.2023.08.004.Peer-Reviewed Original ResearchConceptsPartial portal vein ligationNoncirrhotic portal hypertensionCirrhotic patientsVascular endothelial growth factorLiver fibrosisEndothelial growth factorPortal hypertensionSympathetic denervationSympathetic nervesBDL ratsVascular diseaseIdiopathic noncirrhotic portal hypertensionGrowth factorPortal hypertensive patientsPortal vein ligationSympathetic nervous systemMechanisms of lymphangiogenesisCeliac ganglionectomyHypertensive patientsLymphatic vessel numberLiver biopsyLiver cirrhosisVein ligationPPVL ratsHepatic lymphatic vesselsThe evolving role of liver sinusoidal endothelial cells in liver health and disease
McConnell M, Kostallari E, Ibrahim S, Iwakiri Y. The evolving role of liver sinusoidal endothelial cells in liver health and disease. Hepatology 2023, 78: 649-669. PMID: 36626620, PMCID: PMC10315420, DOI: 10.1097/hep.0000000000000207.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsLiver diseaseAlcohol-associated liver diseaseEndothelial cellsLiver transplant rejectionIschemia-reperfusion injuryLiver sinusoidal endothelial cellsSinusoidal endothelial cellsPortal hypertensionLiver inflammationMicrovascular thrombosisViral hepatitisReperfusion injuryTransplant rejectionLiver healthLiver pathologyLiver homeostasisLiver regenerationQuiescent phenotypePathological processesUnique populationDiseaseLSECLiver biologyGene expression profilesInflammationHepatic lymphatic vascular system in health and disease
Jeong J, Tanaka M, Iwakiri Y. Hepatic lymphatic vascular system in health and disease. Journal Of Hepatology 2022, 77: 206-218. PMID: 35157960, PMCID: PMC9870070, DOI: 10.1016/j.jhep.2022.01.025.Peer-Reviewed Original ResearchConceptsLiver diseaseNon-alcoholic fatty liver diseaseLymphatic systemFatty liver diseaseCongenital liver diseasesPotential therapeutic strategyHepatic lymphatic systemLiver transplantationPortal hypertensionMalignant tumorsTherapeutic strategiesDisease pathogenesisHepatic physiologyDiseasePathological conditionsSpecific markersLymphatic vesselsVascular systemLymphatic vascular systemOrgansTissue homeostasisHypertensionTransplantationPathophysiologyPathogenesis
2024
Guidelines for the diagnosis and treatment of idiopathic portal hypertension, extrahepatic portal obstruction, and Budd–Chiari syndrome in Japan
Furuichi Y, Kage M, Ohta M, Ohfuji S, Sasaki H, Hidaka H, Yoshida H, Kanto T, Kusano H, Akahoshi T, Obara K, Hashizume M, Kuniyoshi Y, Kawaguchi T, Okubo H, Ishikawa T, Hirooka M, Iwakiri Y, Nio M, Tanaka A. Guidelines for the diagnosis and treatment of idiopathic portal hypertension, extrahepatic portal obstruction, and Budd–Chiari syndrome in Japan. Hepatology Research 2024 PMID: 39364631, DOI: 10.1111/hepr.14118.Peer-Reviewed Original Research
2023
Portal Hypertension in Alcohol-Associated Hepatitis
McConnell M, Iwakiri Y. Portal Hypertension in Alcohol-Associated Hepatitis. Current Hepatology Reports 2023, 22: 67-73. PMID: 37214274, PMCID: PMC10075503, DOI: 10.1007/s11901-023-00601-y.Peer-Reviewed Original ResearchAlcoholic hepatitisPortal hypertensionMajor public health problemAlcohol‐Associated HepatitisLiver-related morbidityPublic health problemReviewThis review articleIntrahepatic vasoconstrictionHospital admissionPortal inflowPerisinusoidal fibrosisHypertensionHealth problemsLiver vasculatureHepatitisClinical perspectiveMultiple possible mechanismsReview articlePossible mechanismPhlebosclerosisVasoconstrictionMorbidityInflammationAdmissionFibrosis
2021
Portal hypertension in cirrhosis: Pathophysiological mechanisms and therapy
Iwakiri Y, Trebicka J. Portal hypertension in cirrhosis: Pathophysiological mechanisms and therapy. JHEP Reports 2021, 3: 100316. PMID: 34337369, PMCID: PMC8318926, DOI: 10.1016/j.jhepr.2021.100316.Peer-Reviewed Original ResearchLiver sinusoidal endothelial cellsHepatic stellate cellsPortal hypertensionChronic liver diseaseIntrahepatic vascular resistanceSinusoidal endothelial cellsExtrahepatic vasculatureVascular resistanceMicrovascular thrombosisHaemodynamic changesLiver diseasePathophysiological mechanismsPortal veinHypertensionPreclinical studiesEffective treatmentStellate cellsPathogenic complexityExtrahepatic mechanismsClinical advancesEffective therapeuticsUnsuccessful translationEndothelial cellsCirrhosisDysregulation
2020
Pathophysiology of Portal Hypertension
Iwakiri Y, Groszmann R. Pathophysiology of Portal Hypertension. 2020, 659-669. DOI: 10.1002/9781119436812.ch51.Peer-Reviewed Original ResearchPortal hypertensionGastroesophageal variceal hemorrhageHyperdynamic circulatory syndromeIntrahepatic portal hypertensionNew blood vessel formationPre-existing vascular bedExtrahepatic circulationVariceal hemorrhageCirculatory syndromeLiver cirrhosisLethal complicationVascular toneVascular bedHypertensionFrequent causeCell-specific modulationPlatelet activationBlood vessel formationOrgans/tissuesVasoconstrictor moleculesCirrhosisTherapeutic purposesVessel formationPathophysiologySubsequent development
2017
Corrigendum to “Hepatic dimethylarginine-dimethylaminohydrolase1 is reduced in cirrhosis and is a target for therapy in portal hypertension” [J Hepatol 62 (2015) 325–331]
Mookerjee RP, Mehta G, Balasubramaniyan V, Mohamed FEZ, Davies N, Sharma V, Iwakiri Y, Jalan R. Corrigendum to “Hepatic dimethylarginine-dimethylaminohydrolase1 is reduced in cirrhosis and is a target for therapy in portal hypertension” [J Hepatol 62 (2015) 325–331]. Journal Of Hepatology 2017, 67: 1124. PMID: 28893453, DOI: 10.1016/j.jhep.2017.08.004.Peer-Reviewed Original ResearchBiology of portal hypertension
McConnell M, Iwakiri Y. Biology of portal hypertension. Hepatology International 2017, 12: 11-23. PMID: 29075990, PMCID: PMC7090883, DOI: 10.1007/s12072-017-9826-x.BooksMeSH KeywordsAnimalsAscitesBlood PlateletsEndothelial CellsEsophageal and Gastric VaricesFibrosisGastrointestinal HemorrhageHepatic EncephalopathyHepatic Veno-Occlusive DiseaseHepatorenal SyndromeHumansHypertension, PortalLiverMiceMicrovesselsModels, AnimalNeovascularization, PathologicRenal InsufficiencySplanchnic CirculationThrombosisVascular ResistanceConceptsLiver sinusoidal endothelial cellsPortal hypertensionMicrovascular thrombosisHepatic stellate cell activationHyperdynamic circulatory syndromeSystemic arterial vasodilationChronic liver diseaseIntrahepatic vascular resistanceSinusoidal portal hypertensionPortal hypertension resultsStellate cell activationSinusoidal endothelial cellsVascular biology researchHepatorenal syndromeGastroesophageal varicesVariceal hemorrhageVascular resistanceArterial vasodilationCirculatory syndromeRenal failureHepatic encephalopathyHypertension resultsLiver diseasePortosystemic shuntMesenteric vasculatureThe portal hypertension syndrome: etiology, classification, relevance, and animal models
Bosch J, Iwakiri Y. The portal hypertension syndrome: etiology, classification, relevance, and animal models. Hepatology International 2017, 12: 1-10. PMID: 29064029, DOI: 10.1007/s12072-017-9827-9.BooksMeSH KeywordsAdrenergic beta-AntagonistsAnimalsAscitesCarcinoma, HepatocellularEarly Detection of CancerEsophageal and Gastric VaricesGastrointestinal HemorrhageHealthy LifestyleHemorrhageHepatic EncephalopathyHepatic VeinsHumansHypertension, PortalHypolipidemic AgentsLigationLiver CirrhosisLiver NeoplasmsModels, AnimalPrognosisSimvastatinConceptsHepatic vein pressure gradientNon-bleeding complicationsPortal hypertensionLiver transplantationDisease stagePortal hypertension syndromeAccurate risk stratificationDevelopment of varicesEndoscopic band ligationAim of treatmentPresent day therapyHealthy life styleBackgroundPortal hypertensionDecompensated patientsHVPG responseRefractory ascitesVariceal bleedingClinical decompensationLarge varicesBand ligationDay therapyHepatic encephalopathyBetter prognosisRisk stratificationEtiologic treatment
2014
Hepatic dimethylarginine-dimethylaminohydrolase1 is reduced in cirrhosis and is a target for therapy in portal hypertension
Mookerjee RP, Mehta G, Balasubramaniyan V, Mohamed Fel Z, Davies N, Sharma V, Iwakiri Y, Jalan R. Hepatic dimethylarginine-dimethylaminohydrolase1 is reduced in cirrhosis and is a target for therapy in portal hypertension. Journal Of Hepatology 2014, 62: 325-331. PMID: 25152204, PMCID: PMC4530584, DOI: 10.1016/j.jhep.2014.08.024.Peer-Reviewed Original ResearchConceptsDDAH-1 expressionMean arterial pressurePortal hypertensionENOS activityDDAH-1Farnesoid X receptor (FXR) agonismFXR agonist obeticholic acidPortal pressure reductionAgonist obeticholic acidPortal pressure measurementsHealthy liver tissueArterial pressureENOS inhibitorHuman cirrhosisBDL ratsObeticholic acidSpecific molecular targetsPlasma ALTReceptor agonismSaline controlsCirrhosisCirrhosis ratsHypertensionOA treatmentTranslational studiesVascular pathobiology in chronic liver disease and cirrhosis – Current status and future directions
Iwakiri Y, Shah V, Rockey DC. Vascular pathobiology in chronic liver disease and cirrhosis – Current status and future directions. Journal Of Hepatology 2014, 61: 912-924. PMID: 24911462, PMCID: PMC4346093, DOI: 10.1016/j.jhep.2014.05.047.BooksConceptsChronic liver diseasePortal hypertensionLiver diseaseLiver fibrosis/cirrhosisVascular cellsMesenteric vascular circulationFibrosis/cirrhosisDynamic vascular changesCollateral vessel formationHepatic stellate cellsSinusoidal endothelial cellsGrowth factor pathwaysGrowth factor βExtrahepatic circulationExtrahepatic vasculatureArterial vasodilationLiver injuryVascular changesVasoactive peptidesHypertensionVascular pathobiologySystemic circulationStellate cellsVascular processesLiver vasculaturePathophysiology of Portal Hypertension
Iwakiri Y. Pathophysiology of Portal Hypertension. Clinics In Liver Disease 2014, 18: 281-291. PMID: 24679494, PMCID: PMC3971388, DOI: 10.1016/j.cld.2013.12.001.BooksConceptsPortal hypertensionBlood flowHyperdynamic circulatory syndromeIntrahepatic vascular resistancePortal blood flowVascular resistanceArterial vasodilationCirculatory syndromeEsophageal varicesLiver cirrhosisMajor complicationsLiver diseaseCollateral vesselsPortal circulationSystemic circulationHypertensionPathologic conditionsClinical researchCirrhosisVaricesVasodilationAscitesComplicationsPathophysiologySyndromePathophysiology of Portal Hypertension
Iwakiri Y, Groszmann R. Pathophysiology of Portal Hypertension. 2014, 3-14. DOI: 10.1007/978-1-4939-0002-2_1.Peer-Reviewed Original ResearchPortal hypertensionLiver diseaseHyperdynamic splanchnic circulationHepatic vascular resistanceSerious liver diseaseExtrahepatic diseaseGastroesophageal varicesVascular resistanceHemodynamic abnormalitiesSplanchnic circulationLethal complicationCirculatory derangementsHypertensionDiseaseCurrent knowledgeVaricesAscitesComplicationsHemorrhageDerangementPathophysiologyRegulatory mechanismsAbnormalitiesFunctional aspects
2013
The lymphatic vascular system in liver diseases: its role in ascites formation
Chung C, Iwakiri Y. The lymphatic vascular system in liver diseases: its role in ascites formation. Clinical And Molecular Hepatology 2013, 19: 99-104. PMID: 23837133, PMCID: PMC3701854, DOI: 10.3350/cmh.2013.19.2.99.BooksConceptsLiver fibrosis/cirrhosisFibrosis/cirrhosisLiver diseasePortal hypertensionAscites formationVascular systemLymphatic vascular systemNormal vascular functionPotential therapeutic targetVascular functionLiver tumorsTherapeutic targetDiseaseLymphatic systemTumor metastasisCirrhosisHypertensionLymphatic vesselsCirculatory systemPathogenesisLymphangiogenesisMetastasisTumorsLiverRole
2012
Intestinal and plasma VEGF levels in cirrhosis: the role of portal pressure
Huang H, Haq O, Utsumi T, Sethasine S, Abraldes JG, Groszmann RJ, Iwakiri Y. Intestinal and plasma VEGF levels in cirrhosis: the role of portal pressure. Journal Of Cellular And Molecular Medicine 2012, 16: 1125-1133. PMID: 21801303, PMCID: PMC3213314, DOI: 10.1111/j.1582-4934.2011.01399.x.Peer-Reviewed Original ResearchConceptsPlasma VEGF levelsPortal pressureVEGF levelsPortal hypertensionIntestinal VEGFDevelopment of cirrhosisFibrosis/cirrhosisAge-matched controlsGroups of ratsEnd of exposureCirrhosisRatsSignificant positive correlationWeeksHypertensionVEGFInhalationPositive correlationDifferent stagesCarbon tetrachlorideLevelsPathologyControl
2011
Endothelial dysfunction in the regulation of cirrhosis and portal hypertension
Iwakiri Y. Endothelial dysfunction in the regulation of cirrhosis and portal hypertension. Liver International 2011, 32: 199-213. PMID: 21745318, PMCID: PMC3676636, DOI: 10.1111/j.1478-3231.2011.02579.x.BooksConceptsLiver sinusoidal endothelial cellsPortal hypertensionEndothelial dysfunctionArterial vasodilationPortosystemic collateral vesselsProduction of vasodilatorsDevelopment of cirrhosisCollateral vessel formationPathological vascular eventsSinusoidal endothelial cellsExtrahepatic circulationIntrahepatic resistanceOesophageal varicesVascular eventsVascular resistanceVasodilator moleculeCollateral vesselsSinusoidal microcirculationPortal veinHypertensionSystemic circulationBlood flowCirrhosisDysfunctionNitric oxideReticulon 4B (Nogo‐B) is a novel regulator of hepatic fibrosis
Zhang D, Utsumi T, Huang H, Gao L, Sangwung P, Chung C, Shibao K, Okamoto K, Yamaguchi K, Groszmann RJ, Jozsef L, Hao Z, Sessa WC, Iwakiri Y. Reticulon 4B (Nogo‐B) is a novel regulator of hepatic fibrosis. Hepatology 2011, 53: 1306-1315. PMID: 21480333, PMCID: PMC3667398, DOI: 10.1002/hep.24200.Peer-Reviewed Original ResearchConceptsBile duct ligationLiver fibrosisPortal pressureKO micePortal hypertensionReticulon 4BWT mice 4 weeksMice 4 weeksFibrosis/cirrhosisSham-operated controlsB knockout miceHepatic stellate cellsPotential therapeutic targetHuman liver sectionsAbsence of NogoGrowth factor β stimulationMechanism of NogoTGFβ/SMAD2WT miceVascular injuryHepatic fibrosisSham operationCirrhotic liverDuct ligationStellate cells
2010
The Systemic and Splanchnic Circulations
Iwakiri Y. The Systemic and Splanchnic Circulations. Clinical Gastroenterology 2010, 305-321. DOI: 10.1007/978-1-60761-866-9_15.Peer-Reviewed Original ResearchPortal hypertensionArterial vasodilatationSplanchnic circulationSystemic circulationNitric oxideInitiation of vasodilatationSystemic hemodynamic abnormalitiesDevelopment of complicationsSplanchnic blood flowProgressive vasodilatationHemodynamic abnormalitiesIntestinal microcirculationLiver cirrhosisLiver diseaseVasodilator moleculeHypertensionVasodilatationBlood flowCirrhosisPatientsMolecular mechanismsKey eventsSensory mechanismsCirculationComplications
2008
Vascular biology and pathobiology of the liver: Report of a single‐topic symposium
Iwakiri Y, Grisham M, Shah V. Vascular biology and pathobiology of the liver: Report of a single‐topic symposium. Hepatology 2008, 47: 1754-1763. PMID: 18393322, PMCID: PMC2724750, DOI: 10.1002/hep.22203.BooksConceptsPortal hypertensionVascular biologyIschemia-reperfusion injurySingle Topic ConferenceMajority of morbidityClinical sequelaeIR injurySpecific disease syndromesLiver diseaseVascular syndromesVascular diseaseVascular cell signalingHypertensionDisease syndromeLiver cellsSyndromeMajor vascular defectsLiverVascular defectsInjuryDiseasePathobiologyAmerican AssociationCell signalingCirrhosis