2025
Deletion of sphingosine 1-phosphate receptor 1 in myeloid cells reduces hepatic inflammatory macrophages and attenuates MASH
Parthasarathy G, Venkatesan N, Sidhu G, Song M, Liao C, Barrow F, Mauer A, Sehrawat T, Nakao Y, Daniel P, Dasgupta D, Pavelko K, Revelo X, Malhi H. Deletion of sphingosine 1-phosphate receptor 1 in myeloid cells reduces hepatic inflammatory macrophages and attenuates MASH. Hepatology Communications 2025, 9: e0613. PMID: 39899672, DOI: 10.1097/hc9.0000000000000613.Peer-Reviewed Original ResearchConceptsMyeloid cellsMonocyte-derived macrophagesHigh-fatLiver injuryProinflammatory monocyte-derived macrophagesReceptor 1Cell-specific knockout miceMass cytometryT cell subsetsSphingosine 1-phosphate receptor 1Cardiometabolic risk factorsS1P receptor 1Accumulation of monocyte-derived macrophagesImmune cell typesWild-typeLiver inflammatory infiltrationGene ontology pathway analysisWild-type controlsDevelopment of steatohepatitisSphingosine 1-phosphateMitogen-activated protein kinase pathwayT cellsIntrahepatic macrophagesInflammatory infiltrateKnockout mice
2024
Dietary modulation of gut microbiota affects susceptibility to drug-induced liver injury
Pan H, Song D, Wang Z, Yang X, Luo P, Li W, Li Y, Gong M, Zhang C. Dietary modulation of gut microbiota affects susceptibility to drug-induced liver injury. Gut Microbes 2024, 16: 2439534. PMID: 39673542, PMCID: PMC11649229, DOI: 10.1080/19490976.2024.2439534.Peer-Reviewed Original ResearchConceptsGut microbiotaDrug-induced liver injuryIndole-3-lactic acidComposition of human gut microbiotaWestern style dietDietary modulators of gut microbiotaModulation of gut microbiotaHuman gut microbiotaGut microbiota transplantationModulating gut microbiotaSusceptibility to drug-induced liver injuryIncidence of drug-induced liver injuryDietary fiber interventionLiver injuryDiet-induced variationsBile acid metabolismMicrobiotaTranslocation of lipopolysaccharideImprove liver functionSignaling pathwayDietary shiftsMicrobiota transplantationFiber interventionAcid metabolismIntestinal barrierExpanding the spectrum of progressive familial intrahepatic cholestasis: A report of 3 cases
Jiao J, Morotti R, Shafizadeh N, Jain D. Expanding the spectrum of progressive familial intrahepatic cholestasis: A report of 3 cases. American Journal Of Clinical Pathology 2024, 163: 332-339. PMID: 39333837, DOI: 10.1093/ajcp/aqae123.Peer-Reviewed Original ResearchProgressive familial intrahepatic cholestasisATP-binding cassette subfamily B member 4Whole-exome sequencingFamilial intrahepatic cholestasisIntrahepatic cholestasisDiagnostic challengeGroup of autosomal recessive disordersAbnormal liver function testsHomozygous splice site variantDrug-induced liver injuryHeterozygous frameshift mutationHeterozygous missense mutationLiver function testsAged 2 monthsAutosomal recessive disorderSplice site variantHistory of alcoholismABCB4 mutationsPediatric ageLiver biopsyClinical historyRecessive disorderLiver injuryMolecular testingHeterogeneous presentationHepatic GDP-fucose transporter SLC35C1 attenuates cholestatic liver injury and inflammation by inducing CEACAM1 N153 fucosylation
Zhang L, Xie P, Li M, Zhang X, Fei S, Zhao N, Li L, Xie Q, Xu Z, Tang W, Zhu G, Zhu Z, Xu Z, Li J, Zhang C, Boyer J, Chen W, Cai S, Pan Q, Chai J. Hepatic GDP-fucose transporter SLC35C1 attenuates cholestatic liver injury and inflammation by inducing CEACAM1 N153 fucosylation. Hepatology 2024, 81: 774-790. PMID: 38985995, PMCID: PMC11825483, DOI: 10.1097/hep.0000000000001003.Peer-Reviewed Original ResearchMouse model of cholestasisModel of cholestasisCholestatic liver injuryLiver injuryMouse modelCXCL2 expressionSolute carrier familyTandem mass spectrometry analysisPrimary mouse hepatocytesLiver-specific ablationMass spectrometry analysisProtein glycosylationSLC35C1Attenuate cholestatic liver injurySTAT3 signalingBile ductular proliferationBile duct ligationCarrier familyLevels of serumCholic acid feedingMolecular mechanismsIncreased liver necrosisMRNA transcriptsFucosylationCXCL2 mRNA expressionInflammasomes in chronic liver disease: Hepatic injury, fibrosis progression and systemic inflammation
Taru V, Szabo G, Mehal W, Reiberger T. Inflammasomes in chronic liver disease: Hepatic injury, fibrosis progression and systemic inflammation. Journal Of Hepatology 2024, 81: 895-910. PMID: 38908436, PMCID: PMC11881887, DOI: 10.1016/j.jhep.2024.06.016.Peer-Reviewed Original ResearchAcute-on-chronic liver failureChronic liver diseaseLiver disease progressionToll-like receptorsLiver diseasePortal hypertensionLiver failureDisease progressionLiver injuryImmune systemEnd-stage liver diseaseRelease of pro-inflammatory cytokinesInnate immune cellsFlares of inflammationDysfunctional immune systemInflammasome activationPro-inflammatory stateNuclear factor kappa BPro-inflammatory cytokinesAdaptive immune systemFactor kappa BSystemic inflammationLiver parenchymal cellsWhite adipose tissueImmune cellsLiver 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 stainingSafety of naltrexone in patients with cirrhosis
Thompson R, Taddei T, Kaplan D, Rabiee A. Safety of naltrexone in patients with cirrhosis. JHEP Reports 2024, 6: 101095. PMID: 38961852, PMCID: PMC11220533, DOI: 10.1016/j.jhepr.2024.101095.Peer-Reviewed Original ResearchDrug-induced liver injuryRoussel Uclaf Causality Assessment MethodAlcohol use disorderInitiation of naltrexoneSafety of naltrexoneUse disorderRetrospective studyDevelopment of drug-induced liver injuryRoussel Uclaf Causality Assessment Method scoreLiver injuryLiver diseaseRetrospective study of patientsTreatment of alcohol use disordersTreat alcohol use disorderLiver enzyme elevationAlcohol-related cirrhosisCohort of patientsAlkaline phosphatase elevationDiagnosis of cirrhosisStudy of patientsAssociated with developmentCausality Assessment MethodPrescribed naltrexoneDecompensated cirrhosisEnzyme elevationComplement protein signatures in patients with alcohol-associated hepatitis
Taiwo M, Huang E, Pathak V, Bellar A, Welch N, Dasarathy J, Streem D, McClain C, Mitchell M, Barton B, Szabo G, Dasarathy S, Consortium A, Schaefer E, Luther J, Day L, Ouyang X, Suyavaran A, Mehal W, Jacobs J, Goodman R, Rotroff D, Nagy L. Complement protein signatures in patients with alcohol-associated hepatitis. JCI Insight 2024, 9: e174127. PMID: 38573776, PMCID: PMC11141929, DOI: 10.1172/jci.insight.174127.Peer-Reviewed Original ResearchAlcohol-associated hepatitisSevere AHAlcohol use disorderAlcoholic cirrhosisHealthy controlsPredicting 90-day mortalityComplement proteinsSerum proteome of patientsEthanol-induced liver injurySerum proteomeDevelopment of effective therapiesProteome of patientsAssociated with pro-inflammatory cytokinesProtein signaturesPro-inflammatory cytokinesCoagulation factors IINon-invasive biomarkersDiagnostic challengeSerine protease 1Murine modelEffective therapyLiver injuryPrognostic biomarkerHepatic inflammationC1q binding proteinCHAPTER 1 Introduction
Ortiz G, Garcia-Tsao G. CHAPTER 1 Introduction. 2024, 1-6. DOI: 10.1016/b978-0-323-87479-3.00010-7.ChaptersChronic liver diseasePortal hypertensionSustained liver injurySignificant portal hypertensionHealth care utilizationHepatic vein catheterizationStaging of fibrosisBurden of diseaseMost complicationsLiver injuryCare utilizationLiver diseaseVein catheterizationCirrhotic stageLiver stiffnessInvasive proceduresTime of interpretationDiffuse depositionSignificant causeAge groupsNoninvasive meansFibrous tissueSmall riskInterobserver variabilityGold standard
2023
Maresin1 prevents sepsis-induced acute liver injury by suppressing NF-κB/Stat3/MAPK pathways, mitigating inflammation
Sun S, Wang L, Wang J, Chen R, Pei S, Yao S, Lin Y, Yao C, Xia H. Maresin1 prevents sepsis-induced acute liver injury by suppressing NF-κB/Stat3/MAPK pathways, mitigating inflammation. Heliyon 2023, 9: e21883. PMID: 38027581, PMCID: PMC10665730, DOI: 10.1016/j.heliyon.2023.e21883.Peer-Reviewed Original ResearchSepsis-induced acute liver injuryAcute liver injuryAnti-inflammatory effectsLiver injuryNeutrophil infiltrationBacterial loadSurvival rateDocosahexaenoic acidNormal saline 1Peritoneal lavage fluidPro-inflammatory moleculesTreatment of sepsisUncontrolled inflammatory responseAnti-inflammatory moleculesSepsis-induced injuryEffects of MaR1Body weight changesSepsis-related diseasesDose-dependent mannerSaline 1Septic miceCecal ligationLavage fluidLiver functionAcute inflammationOpen‐label, clinical trial extension: Two‐year safety and efficacy results of seladelpar in patients with primary biliary cholangitis
Mayo M, Vierling J, Bowlus C, Levy C, Hirschfield G, Neff G, Galambos M, Gordon S, Borg B, Harrison S, Thuluvath P, Goel A, Shiffman M, Swain M, Jones D, Trivedi P, Kremer A, Aspinall R, Sheridan D, Dörffel Y, Yang K, Choi Y, McWherter C. Open‐label, clinical trial extension: Two‐year safety and efficacy results of seladelpar in patients with primary biliary cholangitis. Alimentary Pharmacology & Therapeutics 2023, 59: 186-200. PMID: 37904314, DOI: 10.1111/apt.17755.Peer-Reviewed Original ResearchConceptsPrimary biliary cholangitisBiliary cholangitisLiver injurySerious treatment-related adverse eventsBiochemical markersLong-term extension studyTreatment-related adverse eventsAnti-pruritic effectsClinical trial extensionsSecondary efficacy analysesTwo-Year SafetyUnexpected histological findingsNon-alcoholic steatohepatitisLong-term safetyAdverse eventsElevated bilirubinComposite endpointDose adjustmentEfficacy analysisHistological findingsTrial extensionEfficacy dataEfficacy resultsSelective peroxisomePatientsClinical and Histopathological Discoveries in Patients with Hepatic Injury and Cholangiopathy Who Have Died of COVID-19: Insights and Opportunities for Intervention
Lim J, Njei B. Clinical and Histopathological Discoveries in Patients with Hepatic Injury and Cholangiopathy Who Have Died of COVID-19: Insights and Opportunities for Intervention. Hepatic Medicine Evidence And Research 2023, 15: 151-164. PMID: 37814605, PMCID: PMC10560482, DOI: 10.2147/hmer.s385133.Peer-Reviewed Original ResearchAcute liver injuryCOVID-19 patientsPre-existing chronic liver diseaseCOVID-19Chronic liver diseaseSARS-CoV-2Immune dysregulationSupportive careBiliary dysfunctionHepatic injuryLiver injuryVascular changesLiver diseaseClinical manifestationsSignificant complicationsLong-term effectsDiagnostic criteriaTherapeutic targetCholangiopathyDiagnostic advancementsPatientsGlobal healthCOVID-19 pandemicInjuryDiverse manifestationsCoffee, adenosine, and the liver
Dranoff J. Coffee, adenosine, and the liver. Purinergic Signalling 2023, 20: 21-28. PMID: 37755557, PMCID: PMC10828332, DOI: 10.1007/s11302-023-09968-5.Peer-Reviewed Original ResearchEndotheliopathy of liver sinusoidal endothelial cells in liver disease
Kondo R, Iwakiri Y, Kage M, Yano H. Endotheliopathy of liver sinusoidal endothelial cells in liver disease. Pathology International 2023, 73: 381-393. PMID: 37589433, DOI: 10.1111/pin.13361.Peer-Reviewed Original ResearchConceptsLiver diseaseSinusoidal endothelial cellsEndothelial cellsLiver injuryLiver tissueIntercellular adhesion molecule-1Improvement of thrombocytopeniaNeutrophil chemotactic mediatorsChronic hepatitis CLiver sinusoidal endothelial cellsSetting of inflammationSevere hepatic inflammationAdhesion molecule-1Largest solid organPotential therapeutic strategyVascular endothelial cellsVon Willebrand factorHepatitis CNeutrophil accumulationHepatic inflammationChemotactic mediatorsIL-6Antithrombotic factorsChemokine ligandSolid organsInhibition of Abelson Tyrosine-Protein Kinase 2 Suppresses the Development of Alcohol-Associated Liver Disease by Decreasing PPARgamma Expression
Malnassy G, Keating C, Gad S, Bridgeman B, Perera A, Hou W, Cotler S, Ding X, Choudhry M, Sun Z, Koleske A, Qiu W. Inhibition of Abelson Tyrosine-Protein Kinase 2 Suppresses the Development of Alcohol-Associated Liver Disease by Decreasing PPARgamma Expression. Cellular And Molecular Gastroenterology And Hepatology 2023, 16: 685-709. PMID: 37460041, PMCID: PMC10520367, DOI: 10.1016/j.jcmgh.2023.07.006.Peer-Reviewed Original ResearchConceptsAlcohol-fed miceLiver diseaseALD pathogenesisPPARγ expressionLiver injuryAlcohol feedingKnockout miceAlcohol-associated liver diseaseLiver tissueC57BL6/J miceAlcohol-induced accumulationAlcohol-induced steatosisOil Red O stainingWild-type miceHypoxia inducible factor 1 subunit alphaTreatment of ALDPPARγ protein expressionRed O stainingLiver-specific knockoutSubsequent lipid accumulationSubsequent RNA sequencingPotential molecular targetsAbl kinase inhibitorsQuantitative polymerase chain reactionLipid droplet formationA Multi-Omic Mosaic Model of Acetaminophen Induced Alanine Aminotransferase Elevation
Monte A, Vest A, Reisz J, Berninzoni D, Hart C, Dylla L, D’Alessandro A, Heard K, Wood C, Pattee J. A Multi-Omic Mosaic Model of Acetaminophen Induced Alanine Aminotransferase Elevation. Journal Of Medical Toxicology 2023, 19: 255-261. PMID: 37231244, PMCID: PMC10212224, DOI: 10.1007/s13181-023-00951-5.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesTricarboxylic acid cycleMitochondrial energy productionLiver injuryGenomic dataALT elevationIdentification of genesTherapeutic doses of APAPAlanine aminotransferase elevationPredicting liver injuryDose of APAPMaltose metabolismAPAP-induced liver injuryMechanism of injuryAssociation studiesGenetic analysisRandomized controlled trialsAminotransferase elevationGenetic variantsAcid cycleClinical outcomesTherapeutic dosesMultiomics approachGenetic controlAPAP liver injuryOrganic Anion Transporting Polypeptide (OATP) 1B3 is a Significant Transporter for Hepatic Uptake of Conjugated Bile Acids in Humans
Pan Q, Zhu G, Xu Z, Zhu J, Ouyang J, Tong Y, Zhao N, Zhang X, Cheng Y, Zhang L, Tan Y, Li J, Zhang C, Chen W, Cai S, Boyer J, Chai J. Organic Anion Transporting Polypeptide (OATP) 1B3 is a Significant Transporter for Hepatic Uptake of Conjugated Bile Acids in Humans. Cellular And Molecular Gastroenterology And Hepatology 2023, 16: 223-242. PMID: 37146714, PMCID: PMC10394288, DOI: 10.1016/j.jcmgh.2023.04.007.Peer-Reviewed Original ResearchConceptsBA uptake transportersBile duct ligationHepatic neutrophil infiltrationCholestatic liver injuryProinflammatory cytokine productionCholic acid dietAdaptive protective responseLiver-specific overexpressionWild-type miceConjugated bile acidsUptake transportersPrimary hepatocytesUDCA feedingNeutrophil infiltrationBDL miceLiver injuryCytokine productionBile flowDuct ligationOrganic anion transporting polypeptide (OATP) 1B3Conjugated BAsTransgenic miceHepatic uptakeBile acidsProtective responseModulating 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 progressionAssessing the Hepatic Safety of Epigallocatechin Gallate (EGCG) in Reproductive-Aged Women
Siblini H, Al-Hendy A, Segars J, González F, Taylor H, Singh B, Flaminia A, Flores V, Christman G, Huang H, Johnson J, Zhang H. Assessing the Hepatic Safety of Epigallocatechin Gallate (EGCG) in Reproductive-Aged Women. Nutrients 2023, 15: 320. PMID: 36678191, PMCID: PMC9861948, DOI: 10.3390/nu15020320.Peer-Reviewed Original ResearchConceptsReproductive-aged womenLiver function testsUterine fibroidsUnexplained infertilityClomiphene citrateSerum liver function testsEpigallocatechin gallateSigns of drugSerum folate levelsGreen tea catechinsHepatic safetyPremenopausal womenProspective cohortDaily doseLiver injuryFunction testsTreatment armsLiver toxicityClinical studiesCommon causeFolate levelsEarly safety assessmentInterim analysisNormal rangeUse of EGCGRunt-related transcription factor-1 ameliorates bile acid–induced hepatic inflammation in cholestasis through JAK/STAT3 signaling
Zhang L, Pan Q, Zhang L, Xia H, Liao J, Zhang X, Zhao N, Xie Q, Liao M, Tan Y, Li Q, Zhu J, Li L, Fan S, Li J, Zhang C, Cai S, Boyer J, Chai J. Runt-related transcription factor-1 ameliorates bile acid–induced hepatic inflammation in cholestasis through JAK/STAT3 signaling. Hepatology 2023, 77: 1866-1881. PMID: 36647589, PMCID: PMC10921919, DOI: 10.1097/hep.0000000000000041.Peer-Reviewed Original ResearchConceptsJAK/STAT3Bile duct ligationInflammatory responseLiver injuryCholestatic patientsTranscription factor 1Duct ligationBile acidsLiver inflammatory responseCholestatic liver injuryHepatic inflammatory responseElevated bile acidsCholic acid dietFactor 1Cholic acid feedingLiver-specific ablationNew therapeutic targetsLiver-specific deletionCholestatic miceHepatic inflammationLiver inflammationInflammatory chemokinesHepatic expressionMouse modelAcid diet
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