Tejasav Sehrawat, MD
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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 markersLong non-coding RNA ACTA2-AS1 promotes ductular reaction by interacting with the p300/ELK1 complex
Navarro-Corcuera A, Sehrawat T, Jalan-Sakrikar N, Gibbons H, Pirius N, Khanal S, Hamdan F, Aseem S, Cao S, Banales J, Kang N, Faubion W, LaRusso N, Shah V, Huebert R. Long non-coding RNA ACTA2-AS1 promotes ductular reaction by interacting with the p300/ELK1 complex. Journal Of Hepatology 2021, 76: 921-933. PMID: 34953958, PMCID: PMC8934273, DOI: 10.1016/j.jhep.2021.12.014.Peer-Reviewed Original ResearchConceptsBile duct ligationDuctular reactionACTA2-AS1KO miceBile duct cellsLPS exposureBiliary diseaseFibrogenic markersInjury modelDuct ligationFibrogenic genesLong non-coding RNAsFl/Cholangiocyte proliferationFibrosisHuman cholangiocytesSGC-CBP30Primary cholangiocytesAbstractTextLiver tissueLAY SUMMARYP300 inhibitorTranscription factorsCholangiocytesDuct cellsMechanical Stretch Increases Expression of CXCL1 in Liver Sinusoidal Endothelial Cells to Recruit Neutrophils, Generate Sinusoidal Microthombi, and Promote Portal Hypertension
Hilscher M, Sehrawat T, Arab J, Zeng Z, Gao J, Liu M, Kostallari E, Gao Y, Simonetto D, Yaqoob U, Cao S, Revzin A, Beyder A, Wang R, Kamath P, Kubes P, Shah V. Mechanical Stretch Increases Expression of CXCL1 in Liver Sinusoidal Endothelial Cells to Recruit Neutrophils, Generate Sinusoidal Microthombi, and Promote Portal Hypertension. Gastroenterology 2019, 157: 193-209.e9. PMID: 30872106, PMCID: PMC6581607, DOI: 10.1053/j.gastro.2019.03.013.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalcium SignalingCapillariesChemokine CXCL1Endothelial CellsExtracellular TrapsHydrolasesHypertension, PortalIn Vitro TechniquesIntegrinsLeukocyte ElastaseLigationLiverMechanotransduction, CellularMiceMice, Inbred C57BLMice, KnockoutNeutrophil InfiltrationPortal PressureProtein-Arginine Deiminase Type 4Receptor, Notch1Stress, MechanicalThrombosisVena Cava, InferiorConceptsLiver sinusoidal endothelial cellsPortal hypertensionBile duct ligationPortal pressureSinusoidal endothelial cellsFormation of NETsPrimary liver sinusoidal endothelial cellsMechanical stretchControl micePeptidyl arginine deiminase type IVTreatment of PHUnderwent bile duct ligationSuprahepatic inferior vena cavaEndothelial cellsLower portal pressureNeutrophil chemoattractant CXCL1Intravital imagingExpression of CXCL1Inferior vena cavaRecruit neutrophilsNeutrophil recruitmentC57BL/6 miceVena cavaLess fibrinSubcutaneous injectionSuper 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 treatmentXIAP Knockdown in Alcohol-Associated Liver Disease Models Exhibits Divergent in vitro and in vivo Phenotypes Owing to a Potential Zonal Inhibitory Role of SMAC
He L, Sehrawat T, Verma V, Navarro-Corcuera A, Sidhu G, Mauer A, Luo X, Katsumi T, Chen J, Shah S, Arab J, Cao S, Kashkar H, Gores G, Malhi H, Shah V. XIAP Knockdown in Alcohol-Associated Liver Disease Models Exhibits Divergent in vitro and in vivo Phenotypes Owing to a Potential Zonal Inhibitory Role of SMAC. Frontiers In Physiology 2021, 12: 664222. PMID: 34025452, PMCID: PMC8138467, DOI: 10.3389/fphys.2021.664222.Peer-Reviewed Original ResearchAlcohol-associated liver diseaseLiver diseaseTreatment of ALDAggravated liver injuryAdvanced liver diseasePrimary hepatocytesBone marrow-derived macrophagesCaspase-3Marrow-derived macrophagesMechanisms of pathogenesisHuman liver tissueInflammatory markersInflammation markersLiver injuryCCl4 modelLiver steatosisClinical trialsCommon causeAnti-apoptotic proteinsKnockout micePeriportal regionHepatocyte apoptosisLiver tissueLow expressionALD modelQuantitative 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 testRegulation 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 2