2012
OPA1 downregulation is involved in sorafenib-induced apoptosis in hepatocellular carcinoma
Zhao X, Tian C, Puszyk W, Ogunwobi O, Cao M, Wang T, Cabrera R, Nelson D, Liu C. OPA1 downregulation is involved in sorafenib-induced apoptosis in hepatocellular carcinoma. Laboratory Investigation 2012, 93: 8-19. PMID: 23108376, PMCID: PMC3860369, DOI: 10.1038/labinvest.2012.144.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCarcinoma, HepatocellularCell Line, TumorCytochromes cDown-RegulationGene Knockdown TechniquesGTP PhosphohydrolasesHumansLiverLiver NeoplasmsMiceMice, SCIDMitochondriaNiacinamidePhenylurea CompoundsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktRaf KinasesRas ProteinsRNA, Small InterferingSignal TransductionSorafenibXenograft Model Antitumor AssaysConceptsHepatocellular carcinomaSorafenib-induced apoptosisHCC xenograft tumor growthOptic atrophy 1HCC cellsPatients' hepatocellular carcinomaNon-tumor tissue samplesAdvanced hepatocellular carcinomaPathogenesis of HCCNovel therapeutic targetTumorigenesis of HCCXenograft tumor growthTumor tissue analysisNormal human primary hepatocytesHuman primary hepatocytesCell growth inhibitionSorafenib treatmentHCC patientsTherapeutic targetExposure of cellsTumor growthMitochondrial injuryPatientsSorafenibOPA1 expressionHistopathologic Resolution of Adult Liver Transplantation Adenovirus Hepatitis With Cidofovir and Intravenous Immunoglobulin: A Case Report
Kerensky T, Hasan A, Schain D, Trikha G, Liu C, Rand K, Soldevila-Pico C, Gupte A. Histopathologic Resolution of Adult Liver Transplantation Adenovirus Hepatitis With Cidofovir and Intravenous Immunoglobulin: A Case Report. Transplantation Proceedings 2012, 45: 293-296. PMID: 23267812, DOI: 10.1016/j.transproceed.2012.06.059.Peer-Reviewed Original ResearchConceptsSolid organ transplant recipientsOrgan transplant recipientsTransplant recipientsHistopathologic resolutionFatal outcomeAdult solid organ transplant recipientsAdult liver transplant recipientsAdult renal transplant recipientsClearance of viremiaCombination of cidofovirPatient's fatal outcomeLiver transplant recipientsRenal transplant recipientsLiver biopsy specimenSpecific treatment modalitiesPositive immunohistochemical stainingAdV diseaseIntravenous cidofovirIntravenous immunoglobulinAdenovirus hepatitisCombination therapyBiopsy specimenCase reportTreatment modalitiesPolymerase chain reaction
2011
Characterization of HCV Interactions with Toll-Like Receptors and RIG-I in Liver Cells
Eksioglu E, Zhu H, Bayouth L, Bess J, Liu H, Nelson D, Liu C. Characterization of HCV Interactions with Toll-Like Receptors and RIG-I in Liver Cells. PLOS ONE 2011, 6: e21186. PMID: 21695051, PMCID: PMC3117876, DOI: 10.1371/journal.pone.0021186.Peer-Reviewed Original ResearchMeSH KeywordsCell DeathCell Line, TumorDEAD Box Protein 58DEAD-box RNA HelicasesDown-RegulationHepacivirusHost-Pathogen InteractionsHumansInterferon-betaLiverProtein BindingReceptors, ImmunologicSignal TransductionTNF-Related Apoptosis-Inducing LigandToll-Like ReceptorsViral Envelope ProteinsVirus ReplicationConceptsHuh7.5 cellsViral replicationHCV chronic patientsExpression of TLR3Toll-like receptorsHCV envelope proteinsExpression levelsRIG-I expressionHCV interactionChronic patientsHCVTRAIL pathwayViral escapeViral infectionInnate immunityViral pathogenesisTLR3Induction of apoptosisAntiviral stateIFN inductionLow expression levelsLiver cellsLH86Envelope proteinIFN
2009
Focal Distribution of Hepatitis C Virus RNA in Infected Livers
Stiffler J, Nguyen M, Sohn J, Liu C, Kaplan D, Seeger C. Focal Distribution of Hepatitis C Virus RNA in Infected Livers. PLOS ONE 2009, 4: e6661. PMID: 19688046, PMCID: PMC2722721, DOI: 10.1371/journal.pone.0006661.Peer-Reviewed Original ResearchConceptsHepatitis C virusHCV RNA levelsHCV RNAHCV replicationRNA levelsBiopsy samplesHCV RNA copy numbersIntrahepatic HCV-RNA levelsISG levelsHepatitis C virus RNAWhole liver sectionsC virus RNAViral RNA levelsFocal distributionInnate immune responseRNA copy numberHCV infectionC virusInfected patientsInfected hepatocytesInterferon betaImmune responseInfected liverLiver sectionsIFNbeta expressionCytolytic T cells induce ceramide-rich platforms in target cell membranes to initiate graft-versus-host disease
Rotolo J, Stancevic B, Lu S, Zhang J, Suh D, King C, Kappel L, Murphy G, Liu C, Fuks Z, van den Brink M, Kolesnick R. Cytolytic T cells induce ceramide-rich platforms in target cell membranes to initiate graft-versus-host disease. Blood 2009, 114: 3693-3706. PMID: 19666872, PMCID: PMC2766684, DOI: 10.1182/blood-2008-11-191148.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBone Marrow TransplantationCD8-Positive T-LymphocytesCell MembraneCeramidesCytokinesDisease Models, AnimalFemaleGraft vs Host DiseaseHepatocytesInterferon-gammaIntestine, SmallLiverLymphocyte ActivationMaleMiceMice, Inbred C57BLMice, Inbred MRL lprMice, SCIDSkinSphingomyelin PhosphodiesteraseSurvival RateT-Lymphocytes, CytotoxicConceptsHost diseaseT cellsT cell proliferation/activationAllogeneic bone marrowAcute inflammatory phaseRelevant mouse modelTumor necrosis factorCytolytic T cellsProliferation/activationCytolytic T lymphocytesPotential new targetsHost target cellsTarget cell membraneAcute graftAcute GVHDGVHD progressionCytokine stormOrgan injuryNecrosis factorGVHDInflammatory phaseRelevant graftT lymphocytesMouse modelBone marrow
2008
Organ-derived dendritic cells have differential effects on alloreactive T cells
Kim T, Terwey T, Zakrzewski J, Suh D, Kochman A, Chen M, King C, Borsotti C, Grubin J, Smith O, Heller G, Liu C, Murphy G, Alpdogan O, van den Brink M. Organ-derived dendritic cells have differential effects on alloreactive T cells. Blood 2008, 111: 2929-2940. PMID: 18178870, PMCID: PMC2254543, DOI: 10.1182/blood-2007-06-096602.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell ProliferationDendritic CellsGene Expression ProfilingGraft vs Host DiseaseHumansIntegrinsIsoantigensLigandsLipopolysaccharidesLiverLymphocyte ActivationMiceMice, Inbred BALB CMice, Inbred C57BLOligonucleotide Array Sequence AnalysisOrgan SpecificityPhenotypeReceptors, Lymphocyte HomingSelectinsSurvival RateT-LymphocytesUp-RegulationConceptsAlloreactive T cellsBone marrow transplantationDendritic cellsT cellsGVHD mortalityLymph nodesAlloreactive donor T cellsGut-draining lymph nodesLiver-derived dendritic cellsNaive allogeneic T cellsMurine bone marrow transplantationPathophysiology of GVHDTarget organ liverDonor T cellsInduction of graftAllogeneic T cellsPeripheral lymph nodesGut-homing phenotypeMurine BMT modelHost diseaseAdoptive transferHoming moleculesMarrow transplantationStimulatory capacityBMT model
2007
β2 integrins separate graft-versus-host disease and graft-versus-leukemia effects
Liang Y, Liu C, Djeu J, Zhong B, Peters T, Scharffetter-Kochanek K, Anasetti C, Yu X. β2 integrins separate graft-versus-host disease and graft-versus-leukemia effects. Blood 2007, 111: 954-962. PMID: 17928532, PMCID: PMC2200850, DOI: 10.1182/blood-2007-05-089573.Peer-Reviewed Original ResearchConceptsT cellsHost diseaseLeukemia effectMurine allogeneic bone marrow transplantation modelAllogeneic bone marrow transplantation modelWild-type donor T cellsAllogeneic hematopoietic stem cell transplantationDonor T-cell infiltrationDonor-derived T cellsHematopoietic stem cell transplantationBeta2 integrinsAnalysis of alloreactivityLess GVHD morbidityDevelopment of GVHDDonor T cellsGVHD target organsT cell infiltrationBone marrow transplantation modelStem cell transplantationWT T cellsT cell activationGVHD morbidityGVL activityGVL effectLess GVHDHepatocellular carcinoma arising from ectopic liver tissue in the pancreas
Cardona D, Grobmyer S, Crawford J, Liu C. Hepatocellular carcinoma arising from ectopic liver tissue in the pancreas. Virchows Archiv 2007, 450: 225-229. PMID: 17216188, DOI: 10.1007/s00428-006-0353-8.Peer-Reviewed Original ResearchConceptsEctopic liver tissueHepatocellular carcinomaLiver tissuePolyclonal carcinoembryonic antigenPreoperative fine-needle aspirationChronic pancreatic diseaseRight upper quadrantFine-needle aspirationAlpha-1 antitrypsinAbdominal painDistal pancreasDistal pancreatectomyDay historyLiver diseaseUpper quadrantHepatocyte antigenNeuroendocrine tumorsHepatoid cellsCanalicular patternNeedle aspirationPancreatic diseaseImmunohistochemistry studiesTrabecular patternGross examinationHispanic men
2005
Defective Jak-Stat Activation in Hepatoma Cells Is Associated with Hepatitis C Viral IFN- Resistance
Zhu H, Nelson D, Crawford J, Liu C. Defective Jak-Stat Activation in Hepatoma Cells Is Associated with Hepatitis C Viral IFN- Resistance. Journal Of Interferon & Cytokine Research 2005, 25: 528-539. PMID: 16181053, DOI: 10.1089/jir.2005.25.528.Peer-Reviewed Original ResearchMeSH KeywordsAntiviral AgentsCarcinoma, HepatocellularCell Line, TumorDNA-Binding ProteinsDrug Resistance, ViralHepacivirusHumansInterferon-alphaLiverLiver NeoplasmsMutationProtein-Tyrosine KinasesRepliconRepressor ProteinsSTAT3 Transcription FactorSuppressor of Cytokine Signaling 3 ProteinSuppressor of Cytokine Signaling ProteinsTrans-ActivatorsTranscription FactorsViral Nonstructural ProteinsConceptsIFN resistanceHCV subgenomic replicon cell culture systemViral infectionChronic hepatitis C viral infectionIFN-sensitive cell linesHepatitis C viral infectionIFN stimulationCell linesRibavirin combination therapyMajority of patientsC viral infectionSTAT3 activationResistant cell linesIFN monotherapyIFN therapySuppressor of cytokineCombination therapyIFN sensitivityJAK-STAT activationIFNPotential mechanismsLong-term cultureCell culture systemExhibit alterationsJAK-STATCCR2 is required for CD8-induced graft-versus-host disease
Terwey T, Kim T, Kochman A, Hubbard V, Lu S, Zakrzewski J, Ramirez-Montagut T, Eng J, Muriglan S, Heller G, Murphy G, Liu C, Budak-Alpdogan T, Alpdogan O, van den Brink M. CCR2 is required for CD8-induced graft-versus-host disease. Blood 2005, 106: 3322-3330. PMID: 16037386, PMCID: PMC1895329, DOI: 10.1182/blood-2005-05-1860.Peer-Reviewed Original ResearchConceptsCC chemokine receptor 2Hematopoietic stem cell transplantationDevelopment of GVHDT cellsT cell migrationHost diseaseAllogeneic hematopoietic stem cell transplantationDonor-derived T cellsControl of CD8Donor-derived CD8GVHD target organsMurine bone marrow transplantation modelBone marrow transplantation modelStem cell transplantationChemokine receptor 2IFN-gamma productionWild-type CD8Alloreactive proliferationDonor CD8GVHD morbidityGVT activityTumor effectMajor complicationsCCR2 signalingCell transplantationImpact of Humoral Immune Response on Distribution and Efficacy of Recombinant Adeno-Associated Virus-Derived Acid -Glucosidase in a Model of Glycogen Storage Disease Type II
Cresawn K, Fraites T, Wasserfall C, Atkinson M, Lewis M, Porvasnik S, Liu C, Mah C, Byrne B. Impact of Humoral Immune Response on Distribution and Efficacy of Recombinant Adeno-Associated Virus-Derived Acid -Glucosidase in a Model of Glycogen Storage Disease Type II. Human Gene Therapy 2005, 16: 68-80. PMID: 15703490, DOI: 10.1089/hum.2005.16.68.Peer-Reviewed Original ResearchConceptsGlycogen storage disease type IIImmune-tolerant miceStorage disease type IIAntibody responseContractile functionImmune responseHumoral immune responseHind limb musclesAcid alpha-glucosidaseCardiorespiratory failureType IIAntibody formationReduced glycogenGlycogen reductionLysosomal storage diseaseSoleus muscleGAA levelsMiceEnzyme levelsSkeletal muscleStorage diseaseLevel of activityMuscleRecombinant adenoAlpha-glucosidase
2004
STAT3 induces anti-hepatitis C viral activity in liver cells
Zhu H, Shang X, Terada N, Liu C. STAT3 induces anti-hepatitis C viral activity in liver cells. Biochemical And Biophysical Research Communications 2004, 324: 518-528. PMID: 15474458, DOI: 10.1016/j.bbrc.2004.09.081.Peer-Reviewed Original ResearchMeSH KeywordsAntiviral AgentsBlotting, NorthernBlotting, WesternCarcinoma, HepatocellularCell LineCell Line, TumorCytokinesDNA-Binding ProteinsDose-Response Relationship, DrugEnzyme InhibitorsGenes, DominantHepacivirusHumansInflammationInterferonsInterleukin-6LigandsLiverLiver NeoplasmsLuciferasesPlasmidsProtein Structure, TertiaryReverse Transcriptase Polymerase Chain ReactionRibavirinRNARNA, MessengerSTAT3 Transcription FactorTime FactorsTrans-ActivatorsTransfectionTyrphostinsConceptsAnti-HCV activityInterferon alphaSTAT3 activationHuman hepatoma cellsHepatitis C virus infectionHCV subgenomic RNA replicationMain therapeutic regimenC virus infectionChronic liver diseaseCytokines IL-6Replicon cell linesIntracellular antiviral stateCell linesHepatoma cellsLiver diseaseTherapeutic regimenActivation of STAT3IL-6Virus infectionEstrogen receptorIFN treatmentAntiviral genesAntiviral pathwaysAntiviral activityAntiviral stateSustained viral response to interferon and ribavirin in liver transplant recipients with recurrent hepatitis C
Abdelmalek M, Firpi R, Soldevila‐Pico C, Reed A, Hemming A, Liu C, Crawford J, Davis G, Nelson D. Sustained viral response to interferon and ribavirin in liver transplant recipients with recurrent hepatitis C. Liver Transplantation 2004, 10: 199-207. PMID: 14762857, DOI: 10.1002/lt.20074.Peer-Reviewed Original ResearchConceptsHepatitis C virusLiver transplant recipientsTransplant recipientsHepatitis CLiver histologyFibrosis stageHCV RNAViral clearanceViral responseCombination therapyDetectable hepatitis C virusRecurrent chronic hepatitis CRecurrent hepatitis C infectionRecurrent hepatitis C virusDetectable HCV RNASustained viral responseChronic hepatitis CInterferon-based treatmentOrthotopic liver transplantationRecurrent hepatitis CHepatitis C infectionInterferon-based therapyRegression of fibrosisGrade of inflammationBaseline histology
2003
Role of CXCR3-induced donor T-cell migration in acute GVHD
Duffner U, Lu B, Hildebrandt G, Teshima T, Williams D, Reddy P, Ordemann R, Clouthier S, Lowler K, Liu C, Gerard C, Cooke K, Ferrara J. Role of CXCR3-induced donor T-cell migration in acute GVHD. Experimental Hematology 2003, 31: 897-902. PMID: 14550805, DOI: 10.1016/s0301-472x(03)00198-x.Peer-Reviewed Original ResearchConceptsRole of CXCR3T cellsAcute GVHDDonor T cell expansionDonor T cell migrationDonor T cellsExpression of CXCR3GVHD target organsDonor cellsEffector T cellsBone marrow transplantation modelDonor T-cell functionMinor histocompatibility antigensT cell expansionWild-type B6Chemokine receptor CXCR3T cell functionWild-type T cellsWild-type donor cellsT cell migrationMigration of donorWild-type donorsAcute graftHost diseaseBMT recipientsLong‐term interleukin 10 therapy in chronic hepatitis C patients has a proviral and anti‐inflammatory effect
Nelson D, Tu Z, Soldevila‐Pico C, Abdelmalek M, Zhu H, Xu Y, Cabrera R, Liu C, Davis G. Long‐term interleukin 10 therapy in chronic hepatitis C patients has a proviral and anti‐inflammatory effect. Hepatology 2003, 38: 859-868. PMID: 14512873, DOI: 10.1002/hep.1840380412.Peer-Reviewed Original ResearchConceptsIL-10HCV RNASerum ALTCytokine productionChronic hepatitis C patientsFunctional T cell analysesSerum HCV RNA levelsHCV-specific CD4Hepatic inflammation scoresIL-10 administrationInterleukin-10 therapyPBMC cytokine productionTh2 dominant profileHCV RNA levelsHepatitis C patientsT cell analysisTh2 cytokine productionAnti-inflammatory effectsAcute flaresC patientsDisease activityMeq/mLViral burdenAdvanced fibrosisLiver biopsyRepifermin (keratinocyte growth factor-2) reduces the severity of graft-versus-host disease while preserving a graft-versus-leukemia effect
Clouthier S, Cooke K, Teshima T, Lowler K, Liu C, Connolly K, Ferrara J. Repifermin (keratinocyte growth factor-2) reduces the severity of graft-versus-host disease while preserving a graft-versus-leukemia effect. Transplantation And Cellular Therapy 2003, 9: 592-603. PMID: 14506661, DOI: 10.1016/s1083-8791(03)00230-1.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Marrow TransplantationCD4 Lymphocyte CountCD8-Positive T-LymphocytesCell DivisionCell Line, TumorDisease Models, AnimalFemaleFibroblast Growth Factor 10Fibroblast Growth FactorsGraft vs Host DiseaseGraft vs Leukemia EffectHumansInterferon-gammaInterleukin-2IntestinesLipopolysaccharidesLiverLymphocyte CountMiceMice, Inbred C57BLMice, Inbred StrainsRecombinant ProteinsSpleenT-LymphocytesT-Lymphocytes, CytotoxicTransplantation, HomologousTumor Necrosis Factor-alphaConceptsBone marrow transplantationAllogeneic bone marrow transplantationAllogeneic BMT recipientsSystemic GVHDGVL effectHost diseaseBMT recipientsTumor necrosis factor alphaBeneficial GVL effectInduction of GVHDSeverity of graftToxicity of GVHDMurine BMT modelBone marrow inoculumNecrosis factor alphaT cell proliferationRecombinant human keratinocyte growth factorHuman keratinocyte growth factorKeratinocyte growth factorLeukemia effectLeukemia responseSerum levelsMarrow transplantationControl miceOrgan histopathologyCD8+ T‐cell interaction with HCV replicon cells: Evidence for both cytokine‐ and cell‐mediated antiviral activity
Liu C, Zhu H, Tu Z, Xu Y, Nelson D. CD8+ T‐cell interaction with HCV replicon cells: Evidence for both cytokine‐ and cell‐mediated antiviral activity. Hepatology 2003, 37: 1335-1342. PMID: 12774012, DOI: 10.1053/jhep.2003.50207.Peer-Reviewed Original ResearchConceptsHepatitis C virusHCV replicon cellsAntiviral activityReplicon cellsHCV repliconMechanisms of HCVAnti-tumor necrosis factor alphaHCV subgenomic replicon systemAnti-interferon gammaDirect cytolytic effectHLA-A11 alleleNecrosis factor alphaHLA class IHost immune responseSubgenomic replicon systemT cell interactionsT-cell bindingHCV nonstructural proteinsCytolytic functionHCV interactionC virusSpecific lysisInfected hepatocytesTNF-alphaAntiviral effectEarly changes in gene expression profiles of hepatic GVHD uncovered by oligonucleotide microarrays
Ichiba T, Teshima T, Kuick R, Misek D, Liu C, Takada Y, Maeda Y, Reddy P, Williams D, Hanash S, Ferrara J. Early changes in gene expression profiles of hepatic GVHD uncovered by oligonucleotide microarrays. Blood 2003, 102: 763-771. PMID: 12663442, DOI: 10.1182/blood-2002-09-2748.Peer-Reviewed Original ResearchMeSH KeywordsAcute-Phase ProteinsAnimalsAntigen PresentationApoptosisBone Marrow TransplantationChemotaxis, LeukocyteExpressed Sequence TagsFemaleGene Expression ProfilingGene Expression RegulationGraft vs Host DiseaseInflammationIntercellular Adhesion Molecule-1Interferon-gammaLiverLymphocyte ActivationMiceMice, Inbred C57BLOligonucleotide Array Sequence AnalysisOrgan SpecificityRadiation ChimeraSpleenT-LymphocytesTransplantation, HomologousTransplantation, IsogeneicConceptsBone marrow transplantationAllogeneic bone marrow transplantationHepatic GVHDAcute GVHDSyngeneic bone marrow transplantationMajor histocompatibility class II moleculesDonor T cellsMajor target organAcute phase proteinsClass II moleculesGene expression profilesIFN-gamma proteinNew potential molecular targetsPotential molecular targetsAcute graftHost diseaseMajor complicationsMarrow transplantationHistologic changesGVHDT cellsEndocrine functionIFN-gammaGastrointestinal tractInterferon gamma
2002
Combination of interferon alfa‐2b and ribavirin in liver transplant recipients with histological recurrent hepatitis C
Firpi R, Abdelmalek M, Soldevila‐Pico C, Reed A, Hemming A, Howard R, van der Werf W, Lauwers G, Liu C, Crawford J, Davis G, Nelson D. Combination of interferon alfa‐2b and ribavirin in liver transplant recipients with histological recurrent hepatitis C. Liver Transplantation 2002, 8: 1000-1006. PMID: 12424712, DOI: 10.1053/jlts.2002.34968.Peer-Reviewed Original ResearchConceptsInterferon alfa-2bLiver transplantationAlfa-2bHistological recurrenceViral eradicationHCV RNAWeek 24Recurrent hepatitis C virus (HCV) infectionHCV RNA 6 monthsHepatitis C virus infectionEnd pointProgressive cholestatic diseaseRecurrent HCV infectionSerum HCV RNAC virus infectionLiver transplant recipientsPrimary end pointRecurrent hepatitis CSecondary end pointsGenotype 1 infectionYears of therapyEnd of treatmentHigh viral loadLiver biopsy resultsRecurrent HCV
2000
Apoptosis and Regeneration of Hepatocytes during Recovery from Transient Hepadnavirus Infections
Guo J, Zhou H, Liu C, Aldrich C, Saputelli J, Whitaker T, Barrasa M, Mason W, Seeger C. Apoptosis and Regeneration of Hepatocytes during Recovery from Transient Hepadnavirus Infections. Journal Of Virology 2000, 74: 1495-1505. PMID: 10627561, PMCID: PMC111485, DOI: 10.1128/jvi.74.3.1495-1505.2000.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesDNA, ViralHepatitis BHepatitis B Virus, WoodchuckHepatitis B, ChronicInterferon-gammaLiverLiver RegenerationMarmotaMolecular Sequence DataReverse Transcriptase Polymerase Chain ReactionTumor Necrosis Factor-alphaViremiaConceptsRegeneration of hepatocytesHepadnavirus infectionTransient infectionHepatitis B virus infectionTumor necrosis factor alphaTransient hepadnavirus infectionsB virus infectionT cell accumulationNecrosis factor alphaCytokine expressionInfected hepatocytesFactor alphaT cellsVirus infectionInterferon gammaInfected liverHistologic analysisLiver tissueInfectionRecovery periodSignificant increaseHepatocytesInitial influxUnknown mechanismApoptosis