2025
Comparison of prognostic accuracy of HCC staging systems in patients undergoing TACE
Kasolowsky V, Gross M, Madoff D, Duncan J, Taddei T, Strazzabosco M, Jaffe A, Chapiro J. Comparison of prognostic accuracy of HCC staging systems in patients undergoing TACE. Clinical Imaging 2025, 120: 110438. PMID: 40049074, DOI: 10.1016/j.clinimag.2025.110438.Peer-Reviewed Original ResearchMeSH KeywordsAgedCarcinoma, HepatocellularChemoembolization, TherapeuticFemaleHumansLiver NeoplasmsMaleMiddle AgedNeoplasm StagingPrognosisRetrospective StudiesConceptsOverall survival of patientsBCLC staging systemTransarterial chemoembolizationOverall survivalStaging systemHepatocellular carcinomaStaging systems of hepatocellular carcinomaHepatocellular carcinoma staging systemsRetrospective single center studyKaplan Meier survival analysisInternational Staging SystemSingle center studyLog-rank testTertiary care centerPredicting overall survivalMeier survival analysisConsecutive patientsPrognostic stratificationStudy endpointPrognostic accuracyCenter studyPrognostic powerStratify outcomesMultivariate analysisPatientsExploring Glypican-3 targeted CAR-NK treatment and potential therapy resistance in hepatocellular carcinoma
Yang L, Pham K, Xi Y, Wu Q, Liu D, Robertson K, Liu C. Exploring Glypican-3 targeted CAR-NK treatment and potential therapy resistance in hepatocellular carcinoma. PLOS ONE 2025, 20: e0317401. PMID: 39841705, PMCID: PMC11753693, DOI: 10.1371/journal.pone.0317401.Peer-Reviewed Original ResearchConceptsGlypican-3Hepatocellular carcinomaCAR-NKNatural killerCell linesCAR-NK therapyCAR-NK cellsTreatment of hepatocellular carcinomaNK cell lineAnti-tumor effectsCancer-related mortalitySuppressed tumor growthPrimary liver cancerInfluence therapeutic outcomesCells in vitroHepatocellular carcinoma treatmentHepG2 cells in vitroNK92MI cellsImmunotherapy strategiesNSG miceImmunotherapy targetOncofetal glycoproteinTherapy resistanceImprove patient outcomesPoor prognosisBile acid synthesis impedes tumor-specific T cell responses during liver cancer
Varanasi S, Chen D, Liu Y, Johnson M, Miller C, Ganguly S, Lande K, LaPorta M, Hoffmann F, Mann T, Teneche M, Casillas E, Mangalhara K, Mathew V, Sun M, Jensen I, Farsakoglu Y, Chen T, Parisi B, Deota S, Havas A, Lee J, Chung H, Schietinger A, Panda S, Williams A, Farber D, Dhar D, Adams P, Feng G, Shadel G, Sundrud M, Kaech S. Bile acid synthesis impedes tumor-specific T cell responses during liver cancer. Science 2025, 387: 192-201. PMID: 39787217, DOI: 10.1126/science.adl4100.Peer-Reviewed Original ResearchMeSH KeywordsAcyltransferasesAnimalsBile Acids and SaltsCarcinoma, HepatocellularCD8-Positive T-LymphocytesCell Line, TumorEndoplasmic Reticulum StressHepatocytesHumansImmune Checkpoint InhibitorsImmunotherapyLithocholic AcidLiver NeoplasmsMiceOxidative StressProgrammed Cell Death 1 ReceptorTumor MicroenvironmentUrsodeoxycholic AcidConceptsTumor-specific T-cell responsesT cell responsesAnti-programmed cell death protein 1Ursodeoxycholic acidCell death protein 1CD8<sup>+</sup> T cellsBile acidsFeatures of human hepatocellular carcinomaImprove tumor immunotherapyInfluence antitumor immunityT cell functionReduced tumor growthBA synthesisLiver cancer modelCancer model systemsHuman hepatocellular carcinomaLandscape of cancerAntitumor immunityTumor immunotherapySecondary bile acidsOrgan-specific metabolitesEndoplasmic reticulum stressT cellsCancer modelsDietary intakeTransarterial chemoembolisation combined with lenvatinib plus pembrolizumab versus dual placebo for unresectable, non-metastatic hepatocellular carcinoma (LEAP-012): a multicentre, randomised, double-blind, phase 3 study
Kudo M, Ren Z, Guo Y, Han G, Lin H, Zheng J, Ogasawara S, Kim J, Zhao H, Li C, Madoff D, Ghobrial R, Kawaoka T, Gerolami R, Ikeda M, Kumada H, El-Khoueiry A, Vogel A, Peng X, Mody K, Dutcus C, Dubrovsky L, Siegel A, Finn R, Llovet J, investigators L. Transarterial chemoembolisation combined with lenvatinib plus pembrolizumab versus dual placebo for unresectable, non-metastatic hepatocellular carcinoma (LEAP-012): a multicentre, randomised, double-blind, phase 3 study. The Lancet 2025, 405: 203-215. PMID: 39798578, DOI: 10.1016/s0140-6736(24)02575-3.Peer-Reviewed Original ResearchConceptsEastern Cooperative Oncology GroupNon-metastatic hepatocellular carcinomaProgression-free survivalTreatment-related adverse eventsPembrolizumab groupPhase 3 studyTransarterial chemoembolisationPlacebo groupHepatocellular carcinomaIntention-to-treatOverall survivalDouble-blindPerformance statusAdverse eventsFollow-upEastern Cooperative Oncology Group performance statusChild-Pugh class A diseaseMedian progression-free survivalSolid Tumors version 1.1Blinded independent central reviewA-fetoprotein levelAlbumin-bilirubin gradeResponse Evaluation CriteriaAs-treated populationMedian follow-up
2024
Targeting immune evasion in hepatocellular carcinoma-initiating cells
Sirera R, Beltrán-Visiedo M, Galluzzi L. Targeting immune evasion in hepatocellular carcinoma-initiating cells. Trends In Immunology 2024, 46: 4-6. PMID: 39721855, DOI: 10.1016/j.it.2024.12.002.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarcinoma, HepatocellularHumansImmune Checkpoint InhibitorsImmune EvasionLiver NeoplasmsNeoplastic Stem CellsTumor EscapeIntegrative multiomic analysis identifies distinct molecular subtypes of NAFLD in a Chinese population
Ding J, Liu H, Zhang X, Zhao N, Peng Y, Shi J, Chen J, Chi X, Li L, Zhang M, Liu W, Zhang L, Ouyang J, Yuan Q, Liao M, Tan Y, Li M, Xu Z, Tang W, Xie C, Li Y, Pan Q, Xu Y, Cai S, Byrne C, Targher G, Ouyang X, Zhang L, Jiang Z, Zheng M, Sun F, Chai J. Integrative multiomic analysis identifies distinct molecular subtypes of NAFLD in a Chinese population. Science Translational Medicine 2024, 16: eadh9940. PMID: 39504356, DOI: 10.1126/scitranslmed.adh9940.Peer-Reviewed Original ResearchConceptsNonalcoholic fatty liver diseaseWhole-genome sequencingHepatocellular carcinomaMolecular subtypesLiver cirrhosisChinese cohort of patientsInfiltration of M1Risk of liver cirrhosisSerum metabolic analysisClinical diagnosisSubtype of nonalcoholic fatty liver diseaseCohort of patientsDevelopment of liver cirrhosisHepatocellular carcinoma developmentIntegrative multiomic analysisHealth care burdenFatty liver diseaseExpression of CYP1A2Urine specimensTreatment strategiesChinese cohortImpaired outcomeM2 macrophagesIntegrative multiomicsLiver diseaseRisk Score for Hepatocellular Cancer in Adults Without Viral Hepatitis or Cirrhosis
Ilagan-Ying Y, Gordon K, Tate J, Lim J, Torgersen J, Re V, Justice A, Taddei T. Risk Score for Hepatocellular Cancer in Adults Without Viral Hepatitis or Cirrhosis. JAMA Network Open 2024, 7: e2443608. PMID: 39504020, PMCID: PMC11541635, DOI: 10.1001/jamanetworkopen.2024.43608.Peer-Reviewed Original ResearchConceptsClassification of DiseasesBody mass indexRisk scoreNinth Revision and International Statistical Classification of DiseasesMass indexAlcohol useInternational Statistical Classification of DiseasesStatistical Classification of DiseasesElectronic health recordsNon-Hispanic blacksInternational Classification of DiseasesNon-Hispanic whitesClinical Modification diagnosisHepatocellular carcinoma risk scoreRisk of hepatocellular carcinomaCox proportional hazards regression modelsValidation sampleHigh-risk individualsProportional hazards regression modelsHCC risk factorsFIB-4Multivariate risk scoreHepatocellular carcinomaHazards regression modelsViral hepatitisInterventional Oncology Meets Immuno-oncology: Combination Therapies for Hepatocellular Carcinoma.
Bitar R, Salem R, Finn R, Greten T, Goldberg S, Chapiro J. Interventional Oncology Meets Immuno-oncology: Combination Therapies for Hepatocellular Carcinoma. Radiology 2024, 313: e232875. PMID: 39560477, PMCID: PMC11605110, DOI: 10.1148/radiol.232875.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, HepatocellularCombined Modality TherapyHumansImmunotherapyLiver NeoplasmsRadiology, InterventionalTumor MicroenvironmentConceptsManagement of hepatocellular carcinomaHepatocellular carcinomaLocoregional therapyClinical trialsImage-guided locoregional therapiesEnd pointsStages of hepatocellular carcinomaTumor microenvironment mechanismsCatheter-directed therapyCombination of immunotherapyProspective clinical trialImaging end pointsStandard of careAdjuvant settingNovel immunotherapiesCombination therapyTherapy resistanceInterventional radiologistsImmunotherapyDisease stageTherapyDisease evolutionNovel biomarkersCarcinomaMicroenvironment mechanismsTitration of RAS alters senescent state and influences tumour initiation
Chan A, Zhu H, Narita M, Cassidy L, Young A, Bermejo-Rodriguez C, Janowska A, Chen H, Gough S, Oshimori N, Zender L, Aitken S, Hoare M, Narita M. Titration of RAS alters senescent state and influences tumour initiation. Nature 2024, 633: 678-685. PMID: 39112713, PMCID: PMC11410659, DOI: 10.1038/s41586-024-07797-z.Peer-Reviewed Original ResearchConceptsTumor typesOncogenic RAS-induced senescenceInfluence tumor initiationProgenitor-like featuresTumor-initiating phenotypeSingle-cell RNA sequencing analysisModel in vivoHCC subclassesModel in vitroHepatocellular carcinomaTumor suppressor mechanismEarly tumorigenesisTumor initiationEarly-onsetProgenitor featuresInduce tumorsSuppressor mechanismTumorLate-onsetRNA sequencing analysisOncogenic stressRas-induced senescenceIn vivoMolecular signaturesOncogene dosageCRISPR-based dissection of microRNA-23a ~ 27a ~ 24-2 cluster functionality in hepatocellular carcinoma
Cui M, Liu Z, Wang S, Bae S, Guo H, Zhou J, Liu R, Wang L. CRISPR-based dissection of microRNA-23a ~ 27a ~ 24-2 cluster functionality in hepatocellular carcinoma. Oncogene 2024, 43: 2708-2721. PMID: 39112518, PMCID: PMC11364504, DOI: 10.1038/s41388-024-03115-z.Peer-Reviewed Original ResearchConceptsMiR-23aMiR-27aCRISPR interferenceCRISPR activationHigh-throughput RNA-seqCell migrationCDK1/cyclin B activityReduced cell growth in vitroMiRNA target predictionCell cycle arrestMiRNA clusterHepatocellular carcinoma cellsCell growth in vitroRNA-seqGene networksTarget predictionCRISPR knockoutOncogenic roleGrowth in vitroCycle arrestMature miRNAsMiRNAsG2/M phaseSignaling pathwayOncogenic functionAcyl-CoA Synthetase Medium-Chain Family Member 5–Mediated Fatty Acid Metabolism Dysregulation Promotes the Progression of Hepatocellular Carcinoma
Yang L, Pham K, Xi Y, Jiang S, Robertson K, Liu C. Acyl-CoA Synthetase Medium-Chain Family Member 5–Mediated Fatty Acid Metabolism Dysregulation Promotes the Progression of Hepatocellular Carcinoma. American Journal Of Pathology 2024, 194: 1951-1966. PMID: 39069168, PMCID: PMC11423759, DOI: 10.1016/j.ajpath.2024.07.002.Peer-Reviewed Original ResearchConceptsDNA methyltransferase 1Fatty acid metabolismAcyl-CoADown-regulationAcid metabolismDecreased STAT3 phosphorylationCell linesPromoter region methylationHepatocellular carcinoma cell lineHepatocellular carcinoma patient samplesDNA methylationFatty acid accumulationDysregulated fatty acid metabolismSTAT3 phosphorylationDecreased cell proliferationHepatocellular carcinomaHepatocellular carcinoma tumor tissuesMethyltransferase 1Region methylationRegulatory mechanismsACSM5Molecular mechanismsMetabolic dysregulationProgression of hepatocellular carcinomaAcid accumulationScreening for Hepatocellular Carcinoma and Survival in Patients With Cirrhosis After Hepatitis C Virus Cure
Mezzacappa C, Kim N, Vutien P, Kaplan D, Ioannou G, Taddei T. Screening for Hepatocellular Carcinoma and Survival in Patients With Cirrhosis After Hepatitis C Virus Cure. JAMA Network Open 2024, 7: e2420963. PMID: 38985470, PMCID: PMC11238019, DOI: 10.1001/jamanetworkopen.2024.20963.Peer-Reviewed Original ResearchConceptsHepatitis C virus cureHepatitis C virusAssociated with improved overall survivalHepatocellular carcinoma diagnosisEarly-stage hepatocellular carcinomaImproved overall survivalOverall survivalHepatocellular carcinomaFollow-upHCC screeningCurative treatmentCumulative incidence of hepatocellular carcinomaDirect-acting antiviral (DAA) therapyCohort studyVeterans Affairs health care systemIncidence of hepatocellular carcinomaRisk of hepatocellular carcinomaCohort study of personsHepatitis C virus cirrhosisDiagnosis of hepatocellular carcinomaLikelihood of curative treatmentYears of follow-upHealth care systemHepatocellular carcinoma screeningHCV-related cirrhosisRole of ammonia and glutamine in the pathogenesis and progression of metabolic dysfunction‐associated steatotic liver disease: A systematic review
Njei B, Al-Ajlouni Y, Ameyaw P, Njei L, Boateng S. Role of ammonia and glutamine in the pathogenesis and progression of metabolic dysfunction‐associated steatotic liver disease: A systematic review. Journal Of Gastroenterology And Hepatology 2024, 39: 1788-1808. PMID: 38763916, DOI: 10.1111/jgh.16603.Peer-Reviewed Original ResearchMeSH KeywordsAmmoniaCarcinoma, HepatocellularDisease ProgressionFatty LiverGlutamate-Ammonia LigaseGlutaminaseGlutamineHumansLiver NeoplasmsConceptsClinical trialsLiver diseaseSteatotic liver diseaseSystematic reviewPersonalized approach to treatmentLarge-scale clinical trialsHuman clinical trialsUrea cycle dysfunctionApproach to treatmentPreclinical findingsPotential therapeutic targetHepatocellular carcinomaLiver cirrhosisLiver functionMeticulous searchDisease progressionSearch of literatureVariable expressionHuman studiesPROSPERO databaseExpression of glutamine synthetaseTherapeutic interventionsPRISMA guidelinesTherapeutic targetMetabolic differencesImpact of HIV Infection on Liver and Cardiovascular Outcomes in Veterans With Metabolic Dysfunction-Associated Steatotic Liver Disease
Wong R, Yang Z, Yeoh A, Do A, Ahmed A, Cheung R. Impact of HIV Infection on Liver and Cardiovascular Outcomes in Veterans With Metabolic Dysfunction-Associated Steatotic Liver Disease. The American Journal Of Gastroenterology 2024, 119: 1841-1848. PMID: 38477465, DOI: 10.14309/ajg.0000000000002760.Peer-Reviewed Original ResearchConceptsImpact of HIV infectionAntiretroviral therapyIncidence of cirrhosisAdverse cardiovascular eventsHIV infectionHepatocellular carcinomaAssociated with greater riskCardiovascular diseaseOverall survivalCardiovascular eventsLiver diseaseSteatotic liver diseaseConcurrent HIV infectionDecreased overall survivalRisk of cirrhosisRisk of liverGreater riskLiver disease progressionPropensity-matched cohortScore-matched cohortCardiovascular disease outcomesUS veteransCardiovascular outcomesDisease progressionPrimary outcomeFatty acid binding protein 5 suppression attenuates obesity-induced hepatocellular carcinoma by promoting ferroptosis and intratumoral immune rewiring
Sun J, Esplugues E, Bort A, Cardelo M, Ruz-Maldonado I, Fernández-Tussy P, Wong C, Wang H, Ojima I, Kaczocha M, Perry R, Suárez Y, Fernández-Hernando C. Fatty acid binding protein 5 suppression attenuates obesity-induced hepatocellular carcinoma by promoting ferroptosis and intratumoral immune rewiring. Nature Metabolism 2024, 6: 741-763. PMID: 38664583, DOI: 10.1038/s42255-024-01019-6.Peer-Reviewed Original ResearchConceptsFatty acid binding protein 5Tumor-associated macrophagesHepatocellular carcinomaImmunosuppressive phenotype of tumor-associated macrophagesIncreased CD8+ T cell activationCD8+ T cell activationPhenotype of tumor-associated macrophagesPro-inflammatory tumor microenvironmentCo-stimulatory molecules CD80T cell activationHepatocellular carcinoma burdenTransformation of hepatocytesBinding protein 5Potential therapeutic approachImmunosuppressive phenotypeTumor microenvironmentFerroptosis-induced cell deathMale miceEnhanced ferroptosisTherapeutic approachesPharmacological inhibitionGenetic ablationIncreased expressionSingle-cell atlasAnalysis of transformed cellsDesign, Synthesis, and Mechanistic Studies of (R)‑3-Amino-5,5-difluorocyclohex-1-ene-1-carboxylic Acid as an Inactivator of Human Ornithine Aminotransferase
Devitt A, Vargas A, Zhu W, Soye B, Butun F, Alt T, Kaley N, Ferreira G, Moran G, Kelleher N, Liu D, Silverman R. Design, Synthesis, and Mechanistic Studies of (R)‑3-Amino-5,5-difluorocyclohex-1-ene-1-carboxylic Acid as an Inactivator of Human Ornithine Aminotransferase. ACS Chemical Biology 2024, 19: 1066-1081. PMID: 38630468, PMCID: PMC11274680, DOI: 10.1021/acschembio.4c00022.Peer-Reviewed Original ResearchMeSH KeywordsCarboxylic AcidsCarcinoma, HepatocellularCrystallography, X-RayCyclohexenesDrug DesignEnzyme InhibitorsHumansModels, MolecularOrnithine-Oxo-Acid TransaminaseConceptsActive siteX-ray crystallographyIntact protein mass spectrometryHuman ornithine aminotransferaseNucleophilic additionRing scaffoldMass spectrometryIntermediate speciesProtein mass spectrometryIncreased selectivityTransient state kinetic studiesX-rayMechanistic studiesAdductsSolvent accessibilityKinetic studiesHepatocellular carcinomaProgression of hepatocellular carcinomaMechanism of inactivationStructural evidencePrevalence of hepatocellular carcinomaTreatment of hepatocellular carcinomaCyclohexeneCyclopenteneCrystallographyIntegrative common and rare variant analyses provide insights into the genetic architecture of liver cirrhosis
Ghouse J, Sveinbjörnsson G, Vujkovic M, Seidelin A, Gellert-Kristensen H, Ahlberg G, Tragante V, Rand S, Brancale J, Vilarinho S, Lundegaard P, Sørensen E, Erikstrup C, Bruun M, Jensen B, Brunak S, Banasik K, Ullum H, Verweij N, Lotta L, Baras A, Mirshahi T, Carey D, Kaplan D, Lynch J, Morgan T, Schwantes-An T, Dochtermann D, Pyarajan S, Tsao P, Laisk T, Mägi R, Kozlitina J, Tybjærg-Hansen A, Jones D, Knowlton K, Nadauld L, Ferkingstad E, Björnsson E, Ulfarsson M, Sturluson Á, Sulem P, Pedersen O, Ostrowski S, Gudbjartsson D, Stefansson K, Olesen M, Chang K, Holm H, Bundgaard H, Stender S. Integrative common and rare variant analyses provide insights into the genetic architecture of liver cirrhosis. Nature Genetics 2024, 56: 827-837. PMID: 38632349, PMCID: PMC11096111, DOI: 10.1038/s41588-024-01720-y.Peer-Reviewed Original ResearchMeSH KeywordsAlanine TransaminaseCarcinoma, HepatocellularCase-Control StudiesCohort StudiesFemalegamma-GlutamyltransferaseGenetic Predisposition to DiseaseGenetic VariationGenome-Wide Association StudyHumansLipaseLiver CirrhosisLiver NeoplasmsMaleMembrane ProteinsMultifactorial InheritancePolymorphism, Single NucleotideRisk FactorsConceptsMulti-ancestry genome-wide association studyPolygenic risk scoresRare variant analysisVariant analysisGenome-wide association studiesRare coding variantsHepatocellular carcinomaLow alanine aminotransferaseRisk associationAlcohol intakePrioritized genesGenetic architectureNear genesAlanine aminotransferaseRisk scoreHepatic lipid metabolismAssociation studiesLiver cirrhosisGenetic underpinningsPNPLA3 p.Cirrhosis to hepatocellular carcinomaRisk of cirrhosisLiver function testsLipid metabolismGenesEffect of Incomplete Cryoablation and Matrix Metalloproteinase Inhibition on Intratumoral CD8+ T-Cell Infiltration in Murine Hepatocellular Carcinoma.
Shewarega A, Santana J, Nam D, Berz A, Tefera J, Kahl V, Mishra S, Coman D, Duncan J, Roberts S, Wetter A, Madoff D, Chapiro J. Effect of Incomplete Cryoablation and Matrix Metalloproteinase Inhibition on Intratumoral CD8+ T-Cell Infiltration in Murine Hepatocellular Carcinoma. Radiology 2024, 310: e232365. PMID: 38349244, PMCID: PMC10902598, DOI: 10.1148/radiol.232365.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarcinoma, HepatocellularCD8-Positive T-LymphocytesCryosurgeryFemaleLiver NeoplasmsMatrix Metalloproteinase InhibitorsMatrix MetalloproteinasesMiceConceptsT cell infiltrationCD8<sup>+</sup> T cellsMatrix metalloproteinase inhibitionT cellsHepatocellular carcinomaMatrix metalloproteinase inhibitorsMatrix metalloproteinasesResidual tumorCXCR3<sup>+</sup> CD8<sup>+</sup> T cellsCytotoxic CD8<sup>+</sup> T cell infiltrationIntratumoral CD8+ T cell infiltrationCD8+ T cell infiltrationCD8<sup>+</sup> T cell infiltrationMouse model of hepatocellular carcinomaEarly-stage hepatocellular carcinomaImage-guided tumor ablationUnpaired Student's <i>t</i> testModel of hepatocellular carcinomaFirst-line therapyMurine hepatocellular carcinomaT cell subsetsTumor-associated macrophagesMurine HCC modelLocal immune responseFemale BALB/c miceImage-guided High-Dose-Rate Brachytherapy for Hepatocellular Carcinoma Could Be the Ultimate Ablation Tool.
Chapiro J. Image-guided High-Dose-Rate Brachytherapy for Hepatocellular Carcinoma Could Be the Ultimate Ablation Tool. Radiology 2024, 310: e240072. PMID: 38319171, PMCID: PMC10902593, DOI: 10.1148/radiol.240072.Peer-Reviewed Original ResearchMay we actually help clinicians select the best systemic treatment for patients with intermediate‐stage hepatocellular carcinoma?
Giannini E, Strazzabosco M. May we actually help clinicians select the best systemic treatment for patients with intermediate‐stage hepatocellular carcinoma? Liver International 2024, 44: 272-274. PMID: 38289589, DOI: 10.1111/liv.15781.Peer-Reviewed Original Research
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