2025
Concomitant treatment of alcohol associated liver disease and alcohol use disorder in the nontransplant setting: A scoping review
Fathma S, McKee S, Grimshaw A, Boateng S, Fiellin D, Haque L, Mehal W, Banini B. Concomitant treatment of alcohol associated liver disease and alcohol use disorder in the nontransplant setting: A scoping review. Alcohol Clinical And Experimental Research 2025, 49: 1631-1639. PMID: 40650432, DOI: 10.1111/acer.70112.Peer-Reviewed Original ResearchConceptsTreatment of alcohol-associated liver diseaseAlcohol-associated liver diseaseAlcohol use disorderTreatment of alcohol use disordersConcomitant treatmentLiver transplant evaluationLiver diseaseNontransplant settingLiver transplantationProgression of alcohol-associated liver diseaseTransplant evaluationEffective treatmentUse disorderLiver-related deathComprehensive searchAssociated liver diseaseComprehensive search of electronic databasesFrequency of hospitalizationCare modelSearch of electronic databasesDisease courseEmergency department visitsCochrane LibraryAddiction medicineMultidisciplinary care teamTargeted inhibition of pathobiont virulence factor mitigates alcohol-associated liver disease
Yang Y, Duan Y, Lang S, Fondevila M, Schöler D, Harberts A, Cabré N, Chen S, Shao Y, Vervier K, Miyamoto Y, Zhang X, Chu H, Yang L, Tan C, Eckmann L, Bosques-Padilla F, Verna E, Abraldes J, Brown R, Vargas V, Altamirano J, Caballería J, Shawcross D, Louvet A, Lucey M, Mathurin P, Garcia-Tsao G, Bataller R, Stärkel P, Lawley T, Schnabl B. Targeted inhibition of pathobiont virulence factor mitigates alcohol-associated liver disease. Cell Host & Microbe 2025, 33: 957-972.e6. PMID: 40441146, PMCID: PMC12162233, DOI: 10.1016/j.chom.2025.05.003.Peer-Reviewed Original ResearchConceptsEthanol-induced liver diseaseAlcohol-associated liver diseaseAlcohol-associated hepatitisLiver diseaseGenome of Escherichia coliE. coliMetagenomic sequencing of fecal samplesInternational cohort of patientsGenetic manipulation of bacteriaGnotobiotic mouse modelOutcomes of patientsManipulation of bacteriaCohort of patientsScavenger receptor MARCOGlobal health burdenVirulence factorsMetagenomic sequencingGut microbiotaGenetic manipulationDisease progressionMouse modelKupffer cellsKpsMBacterial spreadInternational cohort
2024
Treatment of alcohol use disorder in patients with alcohol-associated liver disease: Innovative approaches and a call to action
Haque L, Zuluaga P, Muga R, Fuster D. Treatment of alcohol use disorder in patients with alcohol-associated liver disease: Innovative approaches and a call to action. Addiction Science & Clinical Practice 2024, 19: 19. PMID: 38504384, PMCID: PMC10949674, DOI: 10.1186/s13722-024-00448-8.Peer-Reviewed Original ResearchConceptsAlcohol-associated liver diseaseAlcohol use disorderLiver diseasePresence of liver cirrhosisTreatment of alcohol use disordersUse disorderInnovative treatment strategiesUnhealthy alcohol usePharmacologic treatment choicesTreating unhealthy alcohol useLiver transplantationLiver cirrhosisTreatment strategiesTreatment choiceEfficacious treatmentLiver deathsPatientsAlcohol useDiseaseLiverTreatmentDisordersCirrhosisTransplantation
2023
Bioactive signalling lipids as drivers of chronic liver diseases
Kaffe E, Tisi A, Magkrioti C, Aidinis V, Mehal W, Flavell R, Maccarrone M. Bioactive signalling lipids as drivers of chronic liver diseases. Journal Of Hepatology 2023, 80: 140-154. PMID: 37741346, DOI: 10.1016/j.jhep.2023.08.029.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, HepatocellularHumansLiverLiver Diseases, AlcoholicLiver NeoplasmsNon-alcoholic Fatty Liver DiseasePhospholipidsConceptsChronic liver diseaseLiver diseasePrevalent chronic liver diseaseBioactive lipidsPotential therapeutic targetG protein-coupled receptorsProtein-coupled receptorsTherapeutic targetPoly-unsaturated fatty acidsMalignant transformationPotent modulatorEnergy homeostasisDiseaseCell proliferationSignaling lipidsTissue repairReceptorsFatty acidsMultiple cellular functionsLipidsBioactive roleBioactive signaling lipidsInflammationProgressionProteomic Panels for Alcohol-Associated Liver Disease: Accurate, but Different Enough From Existing Clinical Tests?
Mezzacappa C, Bhat M. Proteomic Panels for Alcohol-Associated Liver Disease: Accurate, but Different Enough From Existing Clinical Tests? Gastroenterology 2023, 165: 1576. PMID: 37683704, DOI: 10.1053/j.gastro.2023.09.002.Commentaries, Editorials and LettersInhibition 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 formationCatecholamine induces Kupffer cell apoptosis via growth differentiation factor 15 in alcohol-associated liver disease
Kim H, Shim Y, Choi S, Kim M, Lee G, You H, Choi W, Yang K, Ryu T, Kim K, Kim M, Woo C, Chung K, Hong S, Eun H, Kim S, Ko G, Park J, Gao B, Kim W, Jeong W. Catecholamine induces Kupffer cell apoptosis via growth differentiation factor 15 in alcohol-associated liver disease. Experimental & Molecular Medicine 2023, 55: 158-170. PMID: 36631664, PMCID: PMC9898237, DOI: 10.1038/s12276-022-00921-x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisEthanolGrowth Differentiation Factor 15InflammationKupffer CellsLipopolysaccharidesLiverLiver Diseases, AlcoholicMiceConceptsAlcohol-associated liver diseaseApoptotic Kupffer cellsKupffer cellsSingle-cell RNA sequencingCatecholamine levelsLiver diseaseKupffer cell apoptosisPortal bloodGrowth differentiation factor 15Chronic ethanol intakePathogen challengeChronic alcohol exposureApoptotic genesChronic alcohol consumptionB2 adrenergic receptorDifferentiation factor 15Effects of catecholaminesEthanol-fed miceExpression of ADRB2KC apoptosisChronic ethanol-fed miceGrowth differentiation factorRegulatory roleCell apoptosisGenetic ablation
2022
Liver metabolomics identifies bile acid profile changes at early stages of alcoholic liver disease in mice
Charkoftaki G, Tan WY, Berrios-Carcamo P, Orlicky DJ, Golla JP, Garcia-Milian R, Aalizadeh R, Thomaidis NS, Thompson DC, Vasiliou V. Liver metabolomics identifies bile acid profile changes at early stages of alcoholic liver disease in mice. Chemico-Biological Interactions 2022, 360: 109931. PMID: 35429548, PMCID: PMC9364420, DOI: 10.1016/j.cbi.2022.109931.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBile Acids and SaltsEthanolLiverLiver Diseases, AlcoholicMetabolomicsMiceMice, Inbred C57BLConceptsAlcoholic liver diseaseEthanol-consuming miceAlcohol consumptionLiver diseaseDevelopment of ALDBile acid changesChronic alcohol drinkingChronic alcohol consumptionLieber-DeCarli dietAlcohol-induced alterationsGlobal healthcare problemBile acid biosynthesisAlcohol drinkingLiver histopathologyTissue injuryClinical consequencesUntargeted metabolomics analysisEarly stagesComplex pathologyMinimal changesUntargeted metabolomics approachEarly onsetHealthcare problemMiceLiverLipidomics and Redox Lipidomics Indicate Early Stage Alcohol‐Induced Liver Damage
Koelmel JP, Tan WY, Li Y, Bowden JA, Ahmadireskety A, Patt AC, Orlicky DJ, Mathé E, Kroeger NM, Thompson DC, Cochran JA, Golla JP, Kandyliari A, Chen Y, Charkoftaki G, Guingab‐Cagmat J, Tsugawa H, Arora A, Veselkov K, Kato S, Otoki Y, Nakagawa K, Yost RA, Garrett TJ, Vasiliou V. Lipidomics and Redox Lipidomics Indicate Early Stage Alcohol‐Induced Liver Damage. Hepatology Communications 2022, 6: 513-525. PMID: 34811964, PMCID: PMC8870008, DOI: 10.1002/hep4.1825.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkersEthanolFatty LiverFatty Liver, AlcoholicInflammationLipidomicsLiver CirrhosisLiver Diseases, AlcoholicMiceOxidation-ReductionTriglyceridesConceptsAlcoholic fatty liver diseaseEthanol-treated miceFatty liver diseaseAlcohol consumption altersRegulation of triglycerideLiver lipidomeRegulation of phosphatidylcholineHepatic inflammationLiver biopsyLiver diseaseComprehensive time-course studyLiver damageHistological signsEarly biomarkersHistological markersMouse modelTime-course studyLiver tissueTriglyceridesHistological analysisEarly detectionLipid accumulationLiverMajor lipid classesDiet model
2021
Convergent somatic mutations in metabolism genes in chronic liver disease
Ng S, Rouhani F, Brunner S, Brzozowska N, Aitken S, Yang M, Abascal F, Moore L, Nikitopoulou E, Chappell L, Leongamornlert D, Ivovic A, Robinson P, Butler T, Sanders M, Williams N, Coorens T, Teague J, Raine K, Butler A, Hooks Y, Wilson B, Birtchnell N, Naylor H, Davies S, Stratton M, Martincorena I, Rahbari R, Frezza C, Hoare M, Campbell P. Convergent somatic mutations in metabolism genes in chronic liver disease. Nature 2021, 598: 473-478. PMID: 34646017, DOI: 10.1038/s41586-021-03974-6.Peer-Reviewed Original ResearchConceptsSomatic mutationsConvergent evolutionNon-alcoholic fatty liver diseaseMetabolic genesAlcohol-related liver diseaseFatty liver diseaseFrequent convergent evolutionRegulation of metabolic pathwaysLiver diseaseExcess of mutationsLipid droplet metabolismHepatocellular carcinomaBurden of somatic mutationsStorage triacylglycerolsAcquisition of somatic mutationsNuclear exportIndependent clonesChronic liver diseases to hepatocellular carcinomaIncreased clone sizePositive selectionMaster regulatorsTranscription factorsInsulin signalingChronic liver diseaseMetabolic pathwaysAlcohol-induced Hsp90 acetylation is a novel driver of liver sinusoidal endothelial dysfunction and alcohol-related liver disease
Yang Y, Sangwung P, Kondo R, Jung Y, McConnell MJ, Jeong J, Utsumi T, Sessa WC, Iwakiri Y. Alcohol-induced Hsp90 acetylation is a novel driver of liver sinusoidal endothelial dysfunction and alcohol-related liver disease. Journal Of Hepatology 2021, 75: 377-386. PMID: 33675874, PMCID: PMC8292196, DOI: 10.1016/j.jhep.2021.02.028.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationAdultAlcohol DrinkingAnalysis of VarianceAnimalsEndothelial CellsHSP90 Heat-Shock ProteinsHumansLiver Diseases, AlcoholicMiceRatsConceptsEndothelial nitric oxide synthaseAlcohol-induced liver injuryLiver sinusoidal endothelial cellsAlcohol-related liver diseaseLiver injuryLSEC dysfunctionHsp90 acetylationNO productionHistone deacetylase 6Liver diseaseTherapeutic strategiesHeat shock protein 90 (Hsp90) acetylationLiver sinusoidal endothelial dysfunctionSinusoidal endothelial cell dysfunctionMouse liver sinusoidal endothelial cellsEndothelial cell dysfunctionNitric oxide synthaseEthanol-fed miceSinusoidal endothelial dysfunctionPotential therapeutic approachPotential therapeutic strategyNitric oxide productionNew therapeutic strategiesSinusoidal endothelial cellsAcetylation of Hsp90
2020
The lymphatic system in alcohol-associated liver disease
Kondo R, Iwakiri Y. The lymphatic system in alcohol-associated liver disease. Clinical And Molecular Hepatology 2020, 26: 633-638. PMID: 32951411, PMCID: PMC7641555, DOI: 10.3350/cmh.2020.0179.BooksConceptsAlcoholic liver diseaseLymphatic systemLiver diseaseTreatment of ALDAlcohol-associated liver diseaseAlcohol-related diseasesEffects of alcoholHepatic lymphaticsFluid balanceCell surveillanceTherapeutic potentialImmune cell surveillanceDiseaseInterstitial fluid balanceReview articlePathogenesisLymphaticsMitochondrial Double‐Stranded RNA in Exosome Promotes Interleukin‐17 Production Through Toll‐Like Receptor 3 in Alcohol‐associated Liver Injury
Lee J, Shim Y, Seo W, Kim M, Choi W, Kim H, Kim Y, Yang K, Ryu T, Jeong J, Choi H, Eun H, Kim S, Mun H, Yoon J, Jeong W. Mitochondrial Double‐Stranded RNA in Exosome Promotes Interleukin‐17 Production Through Toll‐Like Receptor 3 in Alcohol‐associated Liver Injury. Hepatology 2020, 72: 609-625. PMID: 31849082, PMCID: PMC7297661, DOI: 10.1002/hep.31041.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsExosomesFemaleInterleukin-17Kupffer CellsLiver Diseases, AlcoholicMaleMiceMice, Inbred C57BLMice, KnockoutRNA, Double-StrandedRNA, MitochondrialToll-Like Receptor 3ConceptsAlcohol-associated liver diseaseToll-like receptor 3IL-17A productionCD4<sup>+</sup> T cellsT cellsIL-17AWT miceHepatocytes of WT miceKupffer cellsIL-1B expressionDouble-stranded RNAMitochondrial double-stranded RNAStages of alcohol-associated liver diseaseAlcohol-associated liver injuryProduction of IL-17AReceptor 3MRNA expressionToll-like receptor 3 knockoutWild-type (WT) miceToll-like receptor 3 activationInterleukin-17 productionIL-17A expressionInterleukin (IL)-17AExpression of mitochondrial genesSmall-sized RNARecent advances of sterile inflammation and inter-organ cross-talk in alcoholic liver disease
Shim Y, Jeong W. Recent advances of sterile inflammation and inter-organ cross-talk in alcoholic liver disease. Experimental & Molecular Medicine 2020, 52: 772-780. PMID: 32457490, PMCID: PMC7272465, DOI: 10.1038/s12276-020-0438-5.Peer-Reviewed Original ResearchConceptsDamage-associated molecular patternsAlcoholic liver diseaseNon-parenchymal cellsSterile inflammationLiver diseaseGeneration of damage-associated molecular patternsCellular pattern recognition receptorsMultiple pro-inflammatory cytokinesSpectrum of alcoholic liver diseaseToll-like receptorsPro-inflammatory cytokinesHepatic stellate cellsAlcoholic liver injuryPattern recognition receptorsDouble-stranded RNACross-talkInter-organ cross-talkAlcohol-mediatedBone marrowImmune cellsInduce de novo lipogenesisMitochondrial double-stranded RNALiver injuryKupffer cellsPortal circulationNIK links inflammation to hepatic steatosis by suppressing PPARα in alcoholic liver disease
Li Y, Chen M, Zhou Y, Tang C, Zhang W, Zhong Y, Chen Y, Zhou H, Sheng L. NIK links inflammation to hepatic steatosis by suppressing PPARα in alcoholic liver disease. Theranostics 2020, 10: 3579-3593. PMID: 32206109, PMCID: PMC7069072, DOI: 10.7150/thno.40149.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsEthanolFatty AcidsFatty LiverHepatocytesInflammationLiver Diseases, AlcoholicMaleMAP Kinase Kinase 1MAP Kinase Kinase 2MiceMice, Inbred C57BLMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Oxidation-ReductionPhosphorylationPPAR alphaProtein Serine-Threonine KinasesSignal TransductionConceptsAlcoholic liver diseaseFatty acid oxidationAlcoholic steatosisHepatic fatty acid oxidationHepatocyte-specific deletionHepatic steatosisLiver diseasePPARα agonistAcid oxidationBinge ethanol feedingMain pathological featuresHepatic lipid accumulationEthanol-fed miceRegulation of PPARαRole of NIKALD therapyInflammatory cytokinesPathological featuresUnderlying pathogenesisPharmacological interventionsSteatosisEthanol feedingInflammationPharmacological inhibitionPPARα
2019
Macrophages in Zebrafish Models of Liver Diseases
Shwartz A, Goessling W, Yin C. Macrophages in Zebrafish Models of Liver Diseases. Frontiers In Immunology 2019, 10: 2840. PMID: 31867007, PMCID: PMC6904306, DOI: 10.3389/fimmu.2019.02840.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDisease Models, AnimalHematopoiesisLiver DiseasesLiver Diseases, AlcoholicLiver NeoplasmsLiver RegenerationMacrophagesZebrafishConceptsLiver macrophagesLiver diseaseInflammatory monocyte-derived macrophagesProgression of liver diseaseModels of liver diseaseZebrafish modelChronic liver diseaseNon-alcoholic liver diseaseLiver-resident macrophagesMonocyte-derived macrophagesHepatocellular carcinomaHepatic macrophagesProinflammatory cytokinesLiver disease modelsLiver immunityResident macrophagesKupffer cellsMouse studiesBehavior of macrophagesLiver regenerationMacrophagesTherapeutic interventionsLiver homeostasisLiverDiseaseLiver Transplantation for Alcoholic Liver Disease An Update
Godfrey EL, Stribling R, Rana A. Liver Transplantation for Alcoholic Liver Disease An Update. Clinics In Liver Disease 2019, 23: 127-139. PMID: 30454827, DOI: 10.1016/j.cld.2018.09.007.Peer-Reviewed Original ResearchMeSH KeywordsAftercareAlcohol AbstinenceAlcoholismEligibility DeterminationEnd Stage Liver DiseaseHumansLiver Diseases, AlcoholicLiver TransplantationMalnutritionPatient SelectionConceptsAlcoholic liver diseaseLiver diseaseAbstinence periodBetter long-term outcomesLiver disease burdenSevere alcoholic hepatitisOverall favorable outcomeLong-term outcomesAlcohol use treatmentUnique health concernsMinimum abstinence periodPosttransplantation riskAlcoholic hepatitisLiver transplantationMetabolic complicationsEarly transplantationDisease burdenFavorable outcomeBetter outcomesHealth concernUse treatmentTransplantationOutcomesDiseaseSelection criteria
2018
The multi-dimensional role of intestinal HIFs in liver pathobiology
Ouyang X, Mehal WZ. The multi-dimensional role of intestinal HIFs in liver pathobiology. Journal Of Hepatology 2018, 69: 772-773. PMID: 30104025, DOI: 10.1016/j.jhep.2018.07.012.Peer-Reviewed Original Researchβ-Hydroxybutyrate protects from alcohol-induced liver injury via a Hcar2-cAMP dependent pathway
Chen Y, Ouyang X, Hoque R, Garcia-Martinez I, Yousaf MN, Tonack S, Offermanns S, Dubuquoy L, Louvet A, Mathurin P, Massey V, Schnabl B, Bataller R, Mehal WZ. β-Hydroxybutyrate protects from alcohol-induced liver injury via a Hcar2-cAMP dependent pathway. Journal Of Hepatology 2018, 69: 687-696. PMID: 29705237, PMCID: PMC6098974, DOI: 10.1016/j.jhep.2018.04.004.Peer-Reviewed Original ResearchConceptsAlcohol-induced liver injuryAlcoholic hepatitisAlanine aminotransferase levelsLiver injuryNeutrophil influxAminotransferase levelsΒ-hydroxybutyrateDevelopment of AHPlasma alanine aminotransferase levelsGreater neutrophil influxExcess alcohol intakeAlcoholic liver diseaseLife-threatening conditionExcess alcohol consumptionDependent pathwayHigher plasma alanine aminotransferase levelsIntrahepatic macrophagesLiver inflammationLiver diseaseAlcohol intakeHepatoprotective roleReduced steatosisM2 phenotypeTherapeutic effectHepatitisText Messaging to Reduce Alcohol Relapse in Prelisting Liver Transplant Candidates: A Pilot Feasibility Study
DeMartini KS, Schilsky ML, Palmer A, Fehon DC, Zimbrean P, O'Malley SS, Lee HB, Toll BA. Text Messaging to Reduce Alcohol Relapse in Prelisting Liver Transplant Candidates: A Pilot Feasibility Study. Alcohol Clinical And Experimental Research 2018, 42: 761-769. PMID: 29498753, PMCID: PMC6438371, DOI: 10.1111/acer.13603.Peer-Reviewed Original ResearchConceptsAlcoholic liver diseaseLiver transplant candidatesLiver transplant patientsStandard careEfficacy outcomesTransplant patientsTransplant candidatesFeasibility outcomesTM participantsAlcohol interventionsClinical efficacy outcomesLiver transplantation programPreliminary efficacy outcomesPrimary feasibility outcomePilot feasibility trialPilot feasibility studyRelapse prevention interventionsBetter treatment outcomesLiver diseaseFeasibility trialUnited NetworkTransplantation programIntervention satisfactionTreatment outcomesAlcohol relapse
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