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 termXIAP 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 proteinsEpigenetics of alcohol-related liver diseases
Habash N, Sehrawat T, Shah V, Cao S. Epigenetics of alcohol-related liver diseases. JHEP Reports 2022, 4: 100466. PMID: 35462859, PMCID: PMC9018389, DOI: 10.1016/j.jhepr.2022.100466.Peer-Reviewed Original ResearchAlcohol-related liver diseaseLiver diseaseMajor public health problemChronic liver diseasePublic health problemProinflammatory roleSignificant morbidityMultiple disease statesHealth problemsDisease statesDiseaseClinical applicationNon-coding RNADiagnosisEpigenetic alterationsPrimary causeCurrent knowledgeEpigenetic changesReview articleStudy of epigeneticsHepatologistsMorbidityComplicationsChemokinesPathophysiologyAlcohol-Associated Liver Disease
Liu M, Sehrawat T, Szabo G, Shah V. Alcohol-Associated Liver Disease. 2020, 309-324. DOI: 10.1007/978-3-030-51709-0_20.Peer-Reviewed Original ResearchHepatic stellate cell activation promotes alcohol-induced steatohepatitis through Igfbp3 and SerpinA12
Arab J, Cabrera D, Sehrawat T, Jalan-Sakrikar N, Verma V, Simonetto D, Cao S, Yaqoob U, Leon J, Freire M, Vargas J, De Assuncao T, Kwon J, Guo Y, Kostallari E, Cai Q, Kisseleva T, Oh Y, Arrese M, Huebert R, Shah V. Hepatic stellate cell activation promotes alcohol-induced steatohepatitis through Igfbp3 and SerpinA12. Journal Of Hepatology 2020, 73: 149-160. PMID: 32087348, PMCID: PMC7305991, DOI: 10.1016/j.jhep.2020.02.005.Peer-Reviewed Original ResearchConceptsHepatic stellate cellsAlcohol-induced steatohepatitisNeuropilin-1HSC activationStellate cellsWild-type HSCsLower hepatic triglyceride contentAlcohol-related liver diseaseHepatic stellate cell activationMarkers of steatosisNRP-1 knockdownParenchymal cell injuryDevelopment of steatohepatitisHepatic triglyceride contentEthanol-induced steatosisStellate cell activationAlcoholic hepatitisLipid droplet formationAlcohol feedingLiver diseaseAlcohol damageLess fibrosisLiver fibrosisRegulation of IGFBP3Less inflammation
2024
Portal Fibrosis and the Ductular Reaction: Pathophysiological Role in the Progression of Liver Disease and Translational Opportunities
Gupta V, Sehrawat T, Pinzani M, Strazzabosco M. Portal Fibrosis and the Ductular Reaction: Pathophysiological Role in the Progression of Liver Disease and Translational Opportunities. Gastroenterology 2024 PMID: 39251168, DOI: 10.1053/j.gastro.2024.07.044.Peer-Reviewed Original ResearchLiver diseasePortal fibrosisDuctular reactionPathological repairProgression of liver diseaseCholestatic liver diseaseTranslational opportunitiesChronic liver diseaseProgression of fibrosisCell typesChronic human liver diseaseHuman liver diseaseTumor microenvironmentTherapeutic advancesImmune modulationHistological abnormalitiesVascular changesLiver repairPathophysiological roleFibrosisTreatment prospectsPortal spacesMesenchymal cellsVascular cellsComplex crosstalkLiver Sinusoidal Endothelial Cells Contribute to Portal Hypertension Through Collagen Type IV–Driven Sinusoidal Remodeling
Gan C, Yaqoob U, Lu J, Xie M, Anwar A, Jalan-Sakrikar N, Jerez S, Sehrawat T, Navarro-Corcuera A, Kostallari E, Habash N, Cao S, Shah V. Liver Sinusoidal Endothelial Cells Contribute to Portal Hypertension Through Collagen Type IV–Driven Sinusoidal Remodeling. JCI Insight 2024, 9: e174775. PMID: 38713515, PMCID: PMC11382879, DOI: 10.1172/jci.insight.174775.Peer-Reviewed Original ResearchLiver sinusoidal endothelial cellsPortal hypertensionSinusoidal remodelingSinusoidal endothelial cellsSinusoidal resistanceComplication of liver cirrhosisEndothelial cellsSinusoidal endothelial cells in vitroEnhancer-promoter interactionsEpigenome editing approachesEndothelial cells in vitroChronic liver injuryCells in vitroMouse fibrotic liversCollagen type IVLiver cirrhosisGene mutationsExpression regulationLiver fibrosisLiver injuryEpigenetic repressionLiver diseaseCellular sourceCol4 expressionImmunofluorescence staining
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
2021
Endothelial p300 Promotes Portal Hypertension and Hepatic Fibrosis Through C‐C Motif Chemokine Ligand 2–Mediated Angiocrine Signaling
Gao J, Wei B, Liu M, Hirsova P, Sehrawat T, Cao S, Hu X, Xue F, Yaqoob U, Kang N, Cui H, Pomerantz W, Kostallari E, Shah V. Endothelial p300 Promotes Portal Hypertension and Hepatic Fibrosis Through C‐C Motif Chemokine Ligand 2–Mediated Angiocrine Signaling. Hepatology 2021, 73: 2468-2483. PMID: 33159815, PMCID: PMC8102654, DOI: 10.1002/hep.31617.Peer-Reviewed Original ResearchConceptsLiver sinusoidal endothelial cellsPartial inferior vena cava ligationPortal hypertensionLiver fibrosisLiver injuryMacrophage accumulationCCL2 transcriptionKnockout miceC motif chemokine ligand 2Inferior vena cava ligationP50 knockout miceNuclear factor kappa BVena cava ligationChemokine ligand 2Accumulation of macrophagesPathological inflammatory responsesWild-type miceFactor kappa BSinusoidal endothelial cellsInhibition of p300CCL2 deficiencyPortal pressureLiver diseaseInflammatory cellsCCL2 expression
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 metabolites
2016
THU-396 Prevalence and Correlation of Diabetes with Severity of Chronic Liver Disease and Utility of HBA1C in these Patients as Compared with Oral Glucose Tolerance Test
Sehrawat T, Kohli P, Thour A, Nagra R, Jindal A, Kaur J, Sachdev A, Gupta Y. THU-396 Prevalence and Correlation of Diabetes with Severity of Chronic Liver Disease and Utility of HBA1C in these Patients as Compared with Oral Glucose Tolerance Test. Journal Of Hepatology 2016, 64: s289-s290. DOI: 10.1016/s0168-8278(16)00359-7.Peer-Reviewed Original Research