Featured Publications
Circulating Extracellular Vesicles Carrying Sphingolipid Cargo for the Diagnosis and Dynamic Risk Profiling of Alcoholic Hepatitis
Sehrawat T, Arab J, Liu M, Amrollahi P, Wan M, Fan J, Nakao Y, Pose E, Navarro‐Corcuera A, Dasgupta D, Liao C, He L, Mauer A, Avitabile E, Ventura‐Cots M, Bataller R, Sanyal A, Chalasani N, Heimbach J, Watt K, Gores G, Gines P, Kamath P, Simonetto D, Hu T, Shah V, Malhi H. Circulating Extracellular Vesicles Carrying Sphingolipid Cargo for the Diagnosis and Dynamic Risk Profiling of Alcoholic Hepatitis. Hepatology 2021, 73: 571-585. PMID: 32246544, PMCID: PMC7541595, DOI: 10.1002/hep.31256.Peer-Reviewed Original ResearchConceptsEnd-stage liver diseaseAlcohol-associated cirrhosisAlcoholic hepatitisAH subjectsHealthy controlsHeavy drinkersLiver diseaseEtiology of ESLDEV concentrationEnd-stage liver disease (MELD) scoreExtracellular vesiclesRisk profilingPathogenesis of AHLiver Disease scoreCholestatic liver diseaseNonalcoholic steatohepatitisRisk stratificationClinical criteriaPrognostic performanceDisease scoreDiagnostic biomarkersDisease controlEV countsDiseaseDrinkersAn Open‐Label, Dose‐Escalation Study to Assess the Safety and Efficacy of IL‐22 Agonist F‐652 in Patients With Alcohol‐associated Hepatitis
Arab J, Sehrawat T, Simonetto D, Verma V, Feng D, Tang T, Dreyer K, Yan X, Daley W, Sanyal A, Chalasani N, Radaeva S, Yang L, Vargas H, Ibacache M, Gao B, Gores G, Malhi H, Kamath P, Shah V. An Open‐Label, Dose‐Escalation Study to Assess the Safety and Efficacy of IL‐22 Agonist F‐652 in Patients With Alcohol‐associated Hepatitis. Hepatology 2020, 72: 441-453. PMID: 31774566, PMCID: PMC7250715, DOI: 10.1002/hep.31046.Peer-Reviewed Original ResearchConceptsAlcohol-associated hepatitisSevere alcohol-associated hepatitisSerious adverse eventsMELD scoreDay 28Hepatic regenerationLille scoreAdverse eventsInterleukin-22Randomized placebo-controlled trialDose-escalating studyPlacebo-controlled trialDose-escalation studyMarkers of inflammationComparator cohortOpen labelFirst doseInflammatory markersSerum aminotransferasesSerum cytokinesEfficacy signalsSerum bilirubinMean agePatient cohortRegeneration markersQuantitative assessment of portal hypertension with bi-parametric dual-frequency hepatic MR elastography in mouse models
Li J, Sehrawat T, Chen J, Hilscher M, Glaser K, Arab J, De Assuncao T, Simonetto D, Mounajjed T, Manduca A, Ehman R, Shah V, Yin M. Quantitative assessment of portal hypertension with bi-parametric dual-frequency hepatic MR elastography in mouse models. European Radiology 2020, 31: 2303-2311. PMID: 33026502, PMCID: PMC7981248, DOI: 10.1007/s00330-020-07341-3.Peer-Reviewed Original ResearchConceptsPortal hypertensionPortal pressureHepatic MR elastographyMouse modelHigh diagnostic accuracyDiagnostic accuracyHepatic fibrosisMR elastographyWild-type male miceHypertension mouse modelSignificant portal hypertensionCholestatic liver injuryCholestatic liver diseaseLiver MR elastographySham miceLiver diseaseLiver injuryHepatic congestionLiver fibrosisMale micePreclinical modelsTreatment efficacyFibrosisHypertensionDeLong test
2023
Modulating sphingosine 1-phosphate receptor signaling skews intrahepatic leukocytes and attenuates murine nonalcoholic steatohepatitis
Liao C, Barrow F, Venkatesan N, Nakao Y, Mauer A, Fredrickson G, Song M, Sehrawat T, Dasgupta D, Graham R, Revelo X, Malhi H. Modulating sphingosine 1-phosphate receptor signaling skews intrahepatic leukocytes and attenuates murine nonalcoholic steatohepatitis. Frontiers In Immunology 2023, 14: 1130184. PMID: 37153573, PMCID: PMC10160388, DOI: 10.3389/fimmu.2023.1130184.Peer-Reviewed Original ResearchConceptsMurine nonalcoholic steatohepatitisNonalcoholic steatohepatitisLiver injuryHepatic macrophage accumulationT cellsIntrahepatic leukocytesDietary feedingNKT cellsMacrophage accumulationReceptor antagonismLeukocyte populationsB cellsDouble-negative T cellsReceptor-specific modulationNegative T cellsStandard chow dietImmune cell populationsC57BL/6 male miceCirculating MarkersLiver histologyProinflammatory markersNK cellsOral gavageChow dietNASH progressionLoss of CEACAM1 in endothelial cells causes hepatic fibrosis
Muturi H, Ghadieh H, Abdolahipour R, Stankus H, Belew G, Liu J, Jahromi M, Lee A, Singer B, Angeli-Pahim I, Sehrawat T, Malhi H, Verhulst S, van Grunsven L, Zarrinpar A, Duarte S, Najjar S. Loss of CEACAM1 in endothelial cells causes hepatic fibrosis. Metabolism 2023, 144: 155562. PMID: 37088122, PMCID: PMC10330196, DOI: 10.1016/j.metabol.2023.155562.Peer-Reviewed Original ResearchConceptsFl/Hepatic fibrosisEndothelial lossVisceral obesityImmunohistochemical analysisWild-type HSCsEndothelial cellsHepatic fibrosis stageLiver tissue biopsiesHepatic stellate cellsNF-κB signalingLiver endothelial cellsNF-κB targetsLiver transplantAdult patientsBariatric surgerySystemic inflammationInflammatory infiltrationLiver biopsyNASH pathogenesisInsulin resistanceFibrosis stageInsulin sensitivityHepatic fibrogenesisMale mice
2021
Admission Urinary and Serum Metabolites Predict Renal Outcomes in Hospitalized Patients With Cirrhosis
Bajaj JS, Garcia‐Tsao G, Reddy KR, O’Leary J, Vargas HE, Lai JC, Kamath PS, Tandon P, Subramanian RM, Thuluvath P, Fagan A, Sehrawat T, de la Rosa Rodriguez R, Thacker LR, Wong F. Admission Urinary and Serum Metabolites Predict Renal Outcomes in Hospitalized Patients With Cirrhosis. Hepatology 2021, 74: 2699-2713. PMID: 34002868, PMCID: PMC9338693, DOI: 10.1002/hep.31907.Peer-Reviewed Original ResearchConceptsAcute kidney injuryPrediction of AKIClinical variablesSerum/urineSerum metabolitesBranched-chain amino acid metabolitesLiver disease centerNorth American ConsortiumRole of serumAmino acid metabolitesAdmission urinaryAKI developmentAKI subgroupCirrhosis cohortRenal outcomesRenoprotective measuresKidney injuryAKI predictionCirrhosis severityDialysis initiationHospitalized patientsPoor prognosisUrine metabolomicsEarly initiationSpecific admissionCirculating extracellular vesicles are a biomarker for NAFLD resolution and response to weight loss surgery
Nakao Y, Amrollahi P, Parthasarathy G, Mauer A, Sehrawat T, Vanderboom P, Nair K, Nakao K, Allen A, Hu T, Malhi H. Circulating extracellular vesicles are a biomarker for NAFLD resolution and response to weight loss surgery. Nanomedicine Nanotechnology Biology And Medicine 2021, 36: 102430. PMID: 34174416, PMCID: PMC8418232, DOI: 10.1016/j.nano.2021.102430.Peer-Reviewed Original ResearchConceptsWeight loss surgeryHepatocyte-derived extracellular vesiclesPlasma levelsNAFLD resolutionExtracellular vesiclesWeight loss patientsLogistic regression analysisPlasma extracellular vesiclesNAFLD patientsLipid panelNASH patientsLoss patientsNAFLDInvasive biomarkersPatientsCare testGroup 22EV correlatesSteatosisSurgeryRegression analysisBiomarkersDifferential ultracentrifugationCorrelatesInflammationPerspectives of Inpatients With Cirrhosis and Caregivers on Using Health Information Technology: Cross-sectional Multicenter Study
Acharya C, Sehrawat T, McGuire D, Shaw J, Fagan A, McGeorge S, Olofson A, White M, Gavis E, Kamath P, Bergstrom L, Bajaj J. Perspectives of Inpatients With Cirrhosis and Caregivers on Using Health Information Technology: Cross-sectional Multicenter Study. Journal Of Medical Internet Research 2021, 23: e24639. PMID: 33744844, PMCID: PMC8065567, DOI: 10.2196/24639.Peer-Reviewed Original ResearchConceptsAlcohol-related etiologyHealth IT interventionsPatient-caregiver dyadsGastrointestinal bleedingOpioid useCross-sectional multicenter studyHealth information technology interventionsPatient-associated factorsCaregivers' reluctanceInformation technology interventionsPerspective of inpatientsIT interventionsHepatic encephalopathyMale patientsAdmission reasonMulticenter studyIntervention trialsHealth information technologyCirrhosisStudy burdenCaregiversBleedingReadmissionPatientsRegression analysis
2020
Serum Levels of Metabolites Produced by Intestinal Microbes and Lipid Moieties Independently Associated With Acute-on-Chronic Liver Failure and Death in Patients With Cirrhosis
Bajaj JS, Reddy KR, O'Leary JG, Vargas HE, Lai JC, Kamath PS, Tandon P, Wong F, Subramanian RM, Thuluvath P, Fagan A, White MB, Gavis EA, Sehrawat T, de la Rosa Rodriguez R, Thacker LR, Sikaroodi M, Garcia-Tsao G, Gillevet PM. Serum Levels of Metabolites Produced by Intestinal Microbes and Lipid Moieties Independently Associated With Acute-on-Chronic Liver Failure and Death in Patients With Cirrhosis. Gastroenterology 2020, 159: 1715-1730.e12. PMID: 32687928, PMCID: PMC7680282, DOI: 10.1053/j.gastro.2020.07.019.Peer-Reviewed Original ResearchMeSH KeywordsAcute-On-Chronic Liver FailureAdultAgedBacteriaBiomarkersDatabases, FactualFecesFemaleGastrointestinal MicrobiomeHospital MortalityHumansLipidomicsLipidsLiver CirrhosisMaleMetabolomicsMiddle AgedNorth AmericaPatient AdmissionPredictive Value of TestsPrognosisProspective StudiesRisk AssessmentRisk FactorsTime FactorsConceptsDevelopment of ACLFSerum levelsClinical parametersStool samplesSerum metabolitesEnd-stage liver diseaseWhite blood cell countSerum samplesFecal microbiomeTertiary hepatology centersChronic liver failureDay of admissionMultiple centersTime of admissionBlood cell countNorth American ConsortiumLevels of phospholipidsMetabolomic analysisHepatology centersHospital admissionLiver failureClinical featuresLiver diseaseACLFEstrogen metabolitesIRE1A Stimulates Hepatocyte-Derived Extracellular Vesicles That Promote Inflammation in Mice With Steatohepatitis
Dasgupta D, Nakao Y, Mauer A, Thompson J, Sehrawat T, Liao C, Krishnan A, Lucien F, Guo Q, Liu M, Xue F, Fukushima M, Katsumi T, Bansal A, Pandey M, Maiers J, DeGrado T, Ibrahim S, Revzin A, Pavelko K, Barry M, Kaufman R, Malhi H. IRE1A Stimulates Hepatocyte-Derived Extracellular Vesicles That Promote Inflammation in Mice With Steatohepatitis. Gastroenterology 2020, 159: 1487-1503.e17. PMID: 32574624, PMCID: PMC7666601, DOI: 10.1053/j.gastro.2020.06.031.Peer-Reviewed Original ResearchConceptsX-box binding protein 1Release of EVsHepatocyte-derived extracellular vesiclesSerine palmitoyltransferase genesExtracellular vesiclesSerine palmitoyltransferaseChromatin immunoprecipitationCeramide biosynthesisInflammatory Extracellular VesiclesMonocyte-derived macrophagesUnfolded protein responseNonalcoholic steatohepatitisDiet-induced steatohepatitisGene expression analysisPrimary hepatocytesNumber of EVsBinding protein 1Cultured primary hepatocytesNanoparticle-tracking analysisNanoscale flow cytometryIRE1ALiver tissueRate-limiting enzymeProtein responseExpression analysis