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 countsDiseaseDrinkersThe knowns and unknowns of treatment for alcoholic hepatitis
Sehrawat T, Liu M, Shah V. The knowns and unknowns of treatment for alcoholic hepatitis. The Lancet Gastroenterology & Hepatology 2020, 5: 494-506. PMID: 32277902, PMCID: PMC7238289, DOI: 10.1016/s2468-1253(19)30326-7.Peer-Reviewed Original ResearchConceptsAlcoholic hepatitisLiver diseaseSevere alcoholic hepatitisInflammatory liver diseaseChronic liver diseaseOngoing clinical trialsEffective medical treatmentMedical therapyHigh morbidityClinical trialsHepatitisPreclinical studiesNew therapiesRapid onsetMedical treatmentMyriad complicationsEffective therapeuticsModest effectivenessAlcohol dependencySeries paperPatientsTherapyDiseaseTreatmentLong termAn 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 markersSuper enhancer regulation of cytokine-induced chemokine production in alcoholic hepatitis
Liu M, Cao S, He L, Gao J, Arab J, Cui H, Xuan W, Gao Y, Sehrawat T, Hamdan F, Ventura-Cots M, Argemi J, Pomerantz W, Johnsen S, Lee J, Gao F, Ordog T, Mathurin P, Revzin A, Bataller R, Yan H, Shah V. Super enhancer regulation of cytokine-induced chemokine production in alcoholic hepatitis. Nature Communications 2021, 12: 4560. PMID: 34315876, PMCID: PMC8316465, DOI: 10.1038/s41467-021-24843-w.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChemokinesCytokinesDisease Models, AnimalEndothelial CellsEnhancer Elements, GeneticEpigenesis, GeneticGene Expression RegulationHepatitis, AlcoholicHistonesHumansLipopolysaccharidesLiverMice, Inbred C57BLNeutrophilsNF-kappa BPromoter Regions, GeneticRNA-SeqSignal TransductionTranscription FactorsTumor Necrosis Factor-alphaConceptsAlcoholic hepatitisLiver sinusoidal endothelial cellsChemokine expressionNeutrophil infiltrationLiver neutrophil infiltrationTNFα/NF-κB signalingNF-κB signalingHuman liver explantsElevated chemokine expressionSinusoidal endothelial cellsCXCL expressionChemokine productionCXCL chemokinesCytokine pathwaysCytokines TNFαInflammatory signalingMurine modelLiver explantsTherapeutic potentialPharmacologic inhibitionExtraterminal (BET) proteinsBET inhibitionHuman liverEndothelial cellsAH treatmentRegulation and functional roles of chemokines in liver diseases
Cao S, Liu M, Sehrawat T, Shah V. Regulation and functional roles of chemokines in liver diseases. Nature Reviews Gastroenterology & Hepatology 2021, 18: 630-647. PMID: 33976393, PMCID: PMC9036964, DOI: 10.1038/s41575-021-00444-2.Peer-Reviewed Original ResearchConceptsLiver diseaseImmune cellsAlcohol-associated liver diseaseOngoing clinical trialsRelevant preclinical studiesFunction of chemokinesLiver infiltrationChemokine transcriptionNonalcoholic steatohepatitisChemokine productionCell-type specific productionClinical trialsInflammatory responseFunctional rolePreclinical studiesChemokine functionAnimal modelsChemokinesChemokine biologyLiver homeostasisTherapeutic opportunitiesDiseaseLiver cellsCellsWeight proteinsPost-acute COVID-19 syndrome
Nalbandian A, Sehgal K, Gupta A, Madhavan M, McGroder C, Stevens J, Cook J, Nordvig A, Shalev D, Sehrawat T, Ahluwalia N, Bikdeli B, Dietz D, Der-Nigoghossian C, Liyanage-Don N, Rosner G, Bernstein E, Mohan S, Beckley A, Seres D, Choueiri T, Uriel N, Ausiello J, Accili D, Freedberg D, Baldwin M, Schwartz A, Brodie D, Garcia C, Elkind M, Connors J, Bilezikian J, Landry D, Wan E. Post-acute COVID-19 syndrome. Nature Medicine 2021, 27: 601-615. PMID: 33753937, PMCID: PMC8893149, DOI: 10.1038/s41591-021-01283-z.Peer-Reviewed Original ResearchConceptsPost-acute COVID-19COVID-19Post-acute COVID-19 syndromeSevere acute respiratory syndrome coronavirus 2Dedicated COVID-19 clinicsAcute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Organ-specific sequelaeAcute COVID-19Long-term complicationsMulti-organ diseaseOnset of symptomsPopulation of patientsCOVID-19 syndromeCOVID-19 survivorsCoronavirus disease 2019 (COVID-19) pandemicCOVID-19 clinicSyndrome coronavirus 2Disease 2019 pandemicPatient advocacy groupsGlobal healthcare crisisViral syndromePersistent symptomsMultidisciplinary careCoronavirus 2Extrapulmonary manifestations of COVID-19
Gupta A, Madhavan MV, Sehgal K, Nair N, Mahajan S, Sehrawat TS, Bikdeli B, Ahluwalia N, Ausiello JC, Wan EY, Freedberg DE, Kirtane AJ, Parikh SA, Maurer MS, Nordvig AS, Accili D, Bathon JM, Mohan S, Bauer KA, Leon MB, Krumholz HM, Uriel N, Mehra MR, Elkind MSV, Stone GW, Schwartz A, Ho DD, Bilezikian JP, Landry DW. Extrapulmonary manifestations of COVID-19. Nature Medicine 2020, 26: 1017-1032. PMID: 32651579, DOI: 10.1038/s41591-020-0968-3.Peer-Reviewed Original ResearchConceptsExtrapulmonary manifestationsCOVID-19Acute kidney injuryAcute coronary syndromeSpectrum of manifestationsCoronavirus SARS-CoV-2SARS-CoV-2Coronary syndromeGastrointestinal symptomsKidney injuryOcular symptomsThrombotic complicationsHepatocellular injuryEndothelial damageMyocardial dysfunctionDermatologic complicationsNeurologic illnessRespiratory pathologyImmune responseExtrapulmonary tissuesTherapeutic strategiesEntry receptorTissue damageOrgan systemsInjury
2023
Adding Inflammatory Markers and Refining National Institute on Alcohol Abuse and Alcoholism Criteria Improve Diagnostic Accuracy for Alcohol-associated Hepatitis
Avitabile E, Díaz A, Montironi C, Pérez-Guasch M, Gratacós-Ginès J, Hernández-Évole H, Moreira R, Sehrawat T, Malhi H, Olivas P, Hernández-Gea V, Bataller R, Shah V, Kamath P, Ginès P, Pose E. Adding Inflammatory Markers and Refining National Institute on Alcohol Abuse and Alcoholism Criteria Improve Diagnostic Accuracy for Alcohol-associated Hepatitis. Clinical Gastroenterology And Hepatology 2023, 21: 3080-3088.e9. PMID: 37004974, DOI: 10.1016/j.cgh.2023.03.023.Peer-Reviewed Original ResearchConceptsAlcohol-associated hepatitisAlcohol-related liver diseaseAlcoholic steatohepatitisLiver biopsyDiagnostic accuracyLiver diseaseValidation cohortNIAAA criteriaAlcohol abuseSevere alcohol-associated hepatitisC-reactive proteinGold standardNational InstituteInflammatory markersConsecutive patientsDerivation cohortHistological diagnosisMayo ClinicHospital ClínicTherapeutic studiesAlcoholism criteriaClinical investigatorsConsensus criteriaAbstractTextNoninvasive diagnosis
2022
Mechanotransduction-induced glycolysis epigenetically regulates a CXCL1-dominant angiocrine signaling program in liver sinusoidal endothelial cells in vitro and in vivo
Greuter T, Yaqoob U, Gan C, Jalan-Sakrikar N, Kostallari E, Lu J, Gao J, Sun L, Liu M, Sehrawat TS, Ibrahim SH, Furuta K, Nozickova K, Huang BQ, Gao B, Simons M, Cao S, Shah VH. Mechanotransduction-induced glycolysis epigenetically regulates a CXCL1-dominant angiocrine signaling program in liver sinusoidal endothelial cells in vitro and in vivo. Journal Of Hepatology 2022, 77: 723-734. PMID: 35421427, PMCID: PMC9391258, DOI: 10.1016/j.jhep.2022.03.029.Peer-Reviewed Original ResearchConceptsFocal adhesionsGlycolytic enzymesIsolated focal adhesionsChromosome conformation captureHistone activation marksChromatin immunoprecipitation analysisConformation captureChIP sequencingActivation marksEpigenetic regulationActin dynamicsHistone acetylationRNA sequencingERT2 miceActin polymerizationEndothelial cellsCXCL1 promoterNovel roleIntegrin β1Druggable targetsInhibition of glycolysisNuclear chromatinGlycolysisAngiocrineEnzyme
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 analysisREPLY:
Sehrawat T, Shah V, Malhi H. REPLY:. Hepatology 2021, 73: 472-473. PMID: 32673412, DOI: 10.1002/hep.31464.Peer-Reviewed Original Research
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 metabolitesGIPC-Regulated IGFBP-3 Promotes HSC Migration In Vitro and Portal Hypertension In Vivo Through a β1-Integrin Pathway
Yaqoob U, Luo F, Greuter T, Sakrikar N, Sehrawat T, Lu J, Hu X, Gao J, Kostallari E, Chen J, Arab J, Martin-Mateos R, Cao S, Shah V. GIPC-Regulated IGFBP-3 Promotes HSC Migration In Vitro and Portal Hypertension In Vivo Through a β1-Integrin Pathway. Cellular And Molecular Gastroenterology And Hepatology 2020, 10: 545-559. PMID: 32447051, PMCID: PMC7399184, DOI: 10.1016/j.jcmgh.2020.05.005.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationAdaptor Proteins, Signal TransducingAnimalsBiomarkersCell MovementCells, CulturedDisease Models, AnimalEpigenesis, GeneticGene Knockdown TechniquesHepatic Stellate CellsHistonesHumansHypertension, PortalInsulin-Like Growth Factor Binding Protein 3Integrin beta1Liver CirrhosisMiceMice, KnockoutPhosphorylationPrimary Cell CultureSignal TransductionTransforming Growth Factor betaUp-RegulationConceptsHepatic stellate cellsPortal hypertensionIGFBP-3Quantitative polymerase chain reactionWestern blot analysisLiver fibrosisPolymerase chain reactionHSC migrationChromatin immunoprecipitationChronic liver injury modelInsulin-like growth factorActivation targetGrowth factorQuiescent hepatic stellate cellsIGFBP-3 increaseTransport proteinsChronic liver diseaseChain reactionLiver injury modelIntegrin-dependent phosphorylationHistone 3 lysine 27 acetylationGene regulation changesHSC activation markersEnzyme-linked immunosorbent assayEnzyme-linked immunosorbent