2025
Liver lipid droplet cholesterol content is a key determinant of metabolic dysfunction–associated steatohepatitis
Sakuma I, Gaspar R, Nasiri A, Dufour S, Kahn M, Zheng J, LaMoia T, Guerra M, Taki Y, Kawashima Y, Yimlamai D, Perelis M, Vatner D, Petersen K, Huttasch M, Knebel B, Kahl S, Roden M, Samuel V, Tanaka T, Shulman G. Liver lipid droplet cholesterol content is a key determinant of metabolic dysfunction–associated steatohepatitis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2502978122. PMID: 40310463, PMCID: PMC12067271, DOI: 10.1073/pnas.2502978122.Peer-Reviewed Original ResearchConceptsCholine-deficient l-amino acid-defined high-fat dietBempedoic acidLiver fibrosisLiver diseaseL-amino acid-defined high-fat dietAdvanced liver diseaseCholesterol contentHSD17B13 variantsHigh-fat dietTotal liver cholesterol contentTreated miceActivate signaling pathwaysVariant rs738409Liver cholesterol contentLiver lipidsFibrotic responsePromote inflammationTherapeutic approachesSteatotic liver diseaseDietary cholesterol supplementationFibrosisHuman liver samplesI148MAntisense oligonucleotidesProgressive formSecondary Spontaneous Bacterial Peritonitis Prophylaxis Is Associated With a Higher Rate of Infections other than Spontaneous Bacterial Peritonitis in 2 US-Based National Cirrhosis Cohorts
Silvey S, Patel N, O'Leary J, Jakab S, Patton H, Rogal S, Markley J, Cheung R, Patel A, Morgan T, Bajaj J. Secondary Spontaneous Bacterial Peritonitis Prophylaxis Is Associated With a Higher Rate of Infections other than Spontaneous Bacterial Peritonitis in 2 US-Based National Cirrhosis Cohorts. Clinical And Translational Gastroenterology 2025, 16: e00837. PMID: 40062879, PMCID: PMC12101923, DOI: 10.14309/ctg.0000000000000837.Peer-Reviewed Original ResearchConceptsNon-SBP infectionsUrinary tract infectionSpontaneous bacterial peritonitis prophylaxisTract infectionsMultivariate regressionNational cohort of patientsSpontaneous bacterial peritonitisCohort of patientsBacterial peritonitisRate of infectionCirrhosis cohortAntibiotic overuseHigh riskAntibiotic resistanceC. difficileInfection outcomesPatientsCirrhosisInfectionBacteremiaSBPProphylaxisPneumoniaPeritonitisRecurrenceThe sex differences in diseases progression and prognosis among persons with HIV and HBV coinfection
Yang R, Chen Q, Jiao F, Yu X, Xiong Y. The sex differences in diseases progression and prognosis among persons with HIV and HBV coinfection. Scientific Reports 2025, 15: 4018. PMID: 39893294, PMCID: PMC11787304, DOI: 10.1038/s41598-025-88530-2.Peer-Reviewed Original ResearchConceptsCD4+ T-lymphocyte countT lymphocyte countsEnd-stage-liver diseaseFIB-4 scoreHBV coinfectionFIB-4HBV DNADecline of HBV DNA levelsDisease progressionLong-term surveillance periodRisk factorsPrevalence of liver cirrhosisHBV co-infectionMultivariate logistic regression analysisHBV DNA levelsProgression of liver diseaseIndependent risk factorLiver disease progressionLiver fibrosis levelsAll-cause mortalityMultivariate logistic regressionLogistic regression analysisMale groupSex differencesFemale groupMortality, Hepatic Decompensation, and Cardiovascular Outcomes in Lean vs. Non-lean MASLD Cirrhosis: A Veterans Affairs Cohort Study
Njei B, Mezzacappa C, John B, Serper M, Kaplan D, Taddei T, Mahmud N. Mortality, Hepatic Decompensation, and Cardiovascular Outcomes in Lean vs. Non-lean MASLD Cirrhosis: A Veterans Affairs Cohort Study. Digestive Diseases And Sciences 2025, 70: 802-813. PMID: 39779587, PMCID: PMC11839701, DOI: 10.1007/s10620-024-08764-4.Peer-Reviewed Original ResearchConceptsNon-lean individualsAll-cause mortalityMajor adverse cardiovascular eventsIncreased risk of all-cause mortalityRisk of all-cause mortalityVeterans Health AdministrationRisk of hepatic decompensationPrevalence of diabetesRisk of cardiovascular mortalityHepatic decompensationHigher mortality riskCardiovascular-related mortalityCox proportional hazards modelsCohort study of patientsCardiovascular outcomesIncident major adverse cardiovascular eventsRetrospective cohort study of patientsProportional hazards modelNon-HispanicRetrospective cohort studyCompeting risk regressionHealth AdministrationMultivariate Cox proportional hazards modelLean individualsAssessed associations
2024
Depression and anxiety management in cirrhosis
Zimbrean P, Jakab S. Depression and anxiety management in cirrhosis. Hepatology Communications 2024, 9: e0600. PMID: 39670879, PMCID: PMC11637748, DOI: 10.1097/hc9.0000000000000600.Peer-Reviewed Original ResearchMeSH KeywordsAntidepressive AgentsAnxietyAnxiety DisordersDepressionHumansLiver CirrhosisPrevalencePsychotherapyQuality of LifeConceptsAnxiety disordersAnxiety symptomsPrevalence of generalized anxiety disorderDiagnosis of depressionPrevalence of depressionGeneral populationAnxietyScreening instrumentAnxiety managementTreatment interventionsDepressionPsychotherapyDisordersHealth-related quality of lifeLiver diseaseIntegrated care approachSymptomsHealth-related qualitySevere symptomsPharmacological agentsStand-alone therapyQuality of lifeCare approachAntidepressantsDose adjustmentIntegrative 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 hepatitisGut microbiome profiles to exclude the diagnosis of hepatic encephalopathy in patients with cirrhosis
Bajaj J, O’Leary J, Jakab S, Fagan A, Sikaroodi M, Gillevet P. Gut microbiome profiles to exclude the diagnosis of hepatic encephalopathy in patients with cirrhosis. Gut Microbes 2024, 16: 2392880. PMID: 39189586, PMCID: PMC11352695, DOI: 10.1080/19490976.2024.2392880.Peer-Reviewed Original ResearchConceptsGut microbiome profilesHepatic encephalopathyGut microbiota testMicrobial speciesMicrobiome profilesTraining cohortValidation cohortHE diagnosisStool microbiotaMulticenter prospective cohortDiagnosis of hepatic encephalopathyMulticenter validation cohortNeuropsychological testsNanopore analysisSemi-quantitative questionnaireGutStandard neuropsychological testsProspective cohortIdentified patientsPatientsGold standardCohortDisease processCognitive complaintsDiagnosisSerologic extracellular matrix remodeling markers are related to fibrosis stage and prognosis in a phase 2b trial of simtuzumab in patients with primary sclerosing cholangitis
Thorburn D, Leeming D, Barchuk W, Wang Y, Lu X, Malkov V, Ito K, Bowlus C, Levy C, Goodman Z, Karsdal M, Muir A, Xu J. Serologic extracellular matrix remodeling markers are related to fibrosis stage and prognosis in a phase 2b trial of simtuzumab in patients with primary sclerosing cholangitis. Hepatology Communications 2024, 8: e0467. PMID: 38967589, PMCID: PMC11227354, DOI: 10.1097/hc9.0000000000000467.Peer-Reviewed Original ResearchConceptsPrimary sclerosing cholangitisELF scoreAdvanced fibrosisFibrosis stageFibrosis progressionClinical eventsSclerosing cholangitisExtracellular matrix remodeling markersRemodeling markersPredictors of disease severityPhase 2b trialBaseline to weekPRO-C3Progression to cirrhosisWilcoxon rank sum testMarker of collagen formationType III procollagenModerate diagnostic abilityDiagnosing fibrosis stagesRank sum testSerum markersNoninvasive predictorPrognostic markerModerate prognosisMedian changeScreening 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 cirrhosisGlycolysis in hepatic stellate cells coordinates fibrogenic extracellular vesicle release spatially to amplify liver fibrosis
Khanal S, Liu Y, Bamidele A, Wixom A, Washington A, Jalan-Sakrikar N, Cooper S, Vuckovic I, Zhang S, Zhong J, Johnson K, Charlesworth M, Kim I, Yeon Y, Yoon S, Noh Y, Meroueh C, Timbilla A, Yaqoob U, Gao J, Kim Y, Lucien F, Huebert R, Hay N, Simons M, Shah V, Kostallari E. Glycolysis in hepatic stellate cells coordinates fibrogenic extracellular vesicle release spatially to amplify liver fibrosis. Science Advances 2024, 10: eadn5228. PMID: 38941469, PMCID: PMC11212729, DOI: 10.1126/sciadv.adn5228.Peer-Reviewed Original ResearchConceptsHepatic stellate cellsLiver fibrosisExtracellular vesiclesEV releaseHistone 3 lysine 9 acetylationExtracellular vesicle releaseIncreased EV releaseFibrotic gene expressionNanosized extracellular vesiclesPromoter regionVesicle releasePotential therapeutic targetGene expressionGenetic inhibitionSpatial transcriptomicsStellate cellsGlycolysisUp-regulatedFibrosisTherapeutic targetPericentral zoneLiverPathwayAmplificationExpressionImpact 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 outcomeIntegrative 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 metabolismGenesDivergent role of Mitochondrial Amidoxime Reducing Component 1 (MARC1) in human and mouse
Smagris E, Shihanian L, Mintah I, Bigdelou P, Livson Y, Brown H, Verweij N, Hunt C, Johnson R, Greer T, Hartford S, Hindy G, Sun L, Nielsen J, Halasz G, Lotta L, Murphy A, Sleeman M, Gusarova V. Divergent role of Mitochondrial Amidoxime Reducing Component 1 (MARC1) in human and mouse. PLOS Genetics 2024, 20: e1011179. PMID: 38437227, PMCID: PMC10939284, DOI: 10.1371/journal.pgen.1011179.Peer-Reviewed Original ResearchConceptsAssociation studiesExome-wide association studyHuman genome-wide association studiesGenome-wide association studiesLoss of function variantsFamily enzymesMissense variantsObserved phenotypesFunctional variantsAberrant localizationProtein instabilityAncestry groupsHepatic triglyceride accumulationDivergent rolesLiver phenotypePhysiological functionsTriglyceride accumulationPhenotypeDeletionMouse liverIn vitro studiesHepatic cellsProteinEnzymeKnockout miceImpact of Longitudinal Alcohol Use Patterns on Long-Term Risk of Cirrhosis Among US Veterans With Steatotic Liver Disease
Wong R, Yang Z, Cheung R, Singal A, Do A, Ahmed A, Yeoh A. Impact of Longitudinal Alcohol Use Patterns on Long-Term Risk of Cirrhosis Among US Veterans With Steatotic Liver Disease. Gastroenterology 2024, 166: 1156-1165.e4. PMID: 38428619, DOI: 10.1053/j.gastro.2024.02.032.Peer-Reviewed Original ResearchConceptsRisk of cirrhosisHigh-risk alcoholIncidence of cirrhosisHigh-risk alcohol useLiver diseaseSteatotic liver diseaseLong-term riskAlcohol Use Disorders Identification Test-ConciseAlcohol useFollow-upRisk of liver disease progressionLow-risk alcohol useAbstractText Label="RESULTS">Liver disease progressionAlcohol use assessmentImpact of alcohol useUS veteransBaseline alcohol useAlcohol use patternsDisease progressionCirrhosisReducing alcohol usePatientsLongitudinal alcohol useNo alcohol
2023
Liver Transplantation in a Woman with Mahvash Disease
Robbins J, Halegoua-DeMarzio D, Basu Mallick A, Vijayvergia N, Ganetzky R, Lavu H, Giri V, Miller J, Maley W, Shah A, DiMeglio M, Ambelil M, Yu R, Sato T, Lefler D. Liver Transplantation in a Woman with Mahvash Disease. New England Journal Of Medicine 2023, 389: 1972-1978. PMID: 37991855, DOI: 10.1056/nejmoa2303226.Peer-Reviewed Original ResearchConceptsPortal hypertensionLiver transplantationPancreatic hypertrophyMahvash diseasePancreatic α cell hyperplasiaAbsence of cirrhosisNoncirrhotic portal hypertensionΑ-cell hyperplasiaRare genetic disorderSerum glucagonDefinitive treatmentGlucagon levelsVascular diseaseMedical CenterHypertensionDiseaseAmmonia levelsHyperglucagonemiaGenetic disordersTransplantationHypertrophyGlucagonWomenHematemesisCirrhosisAGA Clinical Practice Update on the Use of Vasoactive Drugs and Intravenous Albumin in Cirrhosis: Expert Review
Garcia-Tsao G, Abraldes J, Rich N, Wong V. AGA Clinical Practice Update on the Use of Vasoactive Drugs and Intravenous Albumin in Cirrhosis: Expert Review. Gastroenterology 2023, 166: 202-210. PMID: 37978969, DOI: 10.1053/j.gastro.2023.10.016.Peer-Reviewed Original ResearchConceptsSpontaneous bacterial peritonitisAcute kidney injuryLarge-volume paracentesisEffective arterial blood volumeVasoactive drugsVariceal hemorrhageArterial blood volumeHRS-AKIUncomplicated ascitesIntravenous albuminVolume statusPractice UpdateBlood volumeChronic liver failure grade 3Best practice advice statementsClinical Practice Updates CommitteeEnd-stage liver diseaseAGA Clinical Practice UpdateForms of AKIIntensive care unit monitoringAGA Governing BoardCombination of vasoconstrictorsInitial endoscopic hemostasisPatient's volume statusClinical Practice UpdatePrevalence and characteristics of hepatitis delta virus infection in patients with hepatitis B in the United States: An analysis of the All-Payer Claims Database
Gish R, Jacobson I, Lim J, Waters-Banker C, Kaushik A, Kim C, Cyhaniuk A, Wong R. Prevalence and characteristics of hepatitis delta virus infection in patients with hepatitis B in the United States: An analysis of the All-Payer Claims Database. Hepatology 2023, 79: 1117-1128. PMID: 37976395, PMCID: PMC11020024, DOI: 10.1097/hep.0000000000000687.Peer-Reviewed Original ResearchConceptsHBV/HDV infectionLiver complicationsAll-Payer Claims DatabaseClaims databaseRisk of liver-related morbidityHepatitis delta virus infectionPrevalence of HDVDelta virus infectionProportion of patientsTime of diagnosisLiver-related morbidityUS insured populationHDV prevalenceHBV populationsHIV infectionCompensated cirrhosisDecompensated cirrhosisHBV infectionDelayed diagnosisHDV infectionHepatitis BViral hepatitisHBV/HDVPatient characteristicsSevere formThe effect of endoscopic gastric plication on portosystemic pressure gradient in patients with nonalcoholic fatty liver disease and compensated advanced chronic liver disease
Jirapinyo P, Thompson C, Garcia-Tsao G, Zucker S, Ryou M. The effect of endoscopic gastric plication on portosystemic pressure gradient in patients with nonalcoholic fatty liver disease and compensated advanced chronic liver disease. Endoscopy 2023, 56: 56-62. PMID: 37532114, DOI: 10.1055/a-2146-8857.Peer-Reviewed Original ResearchMeSH KeywordsHumansLiverLiver CirrhosisNon-alcoholic Fatty Liver DiseasePilot ProjectsProspective StudiesTreatment OutcomeWeight LossConceptsNonalcoholic fatty liver diseaseEndoscopic gastric plicationAdvanced chronic liver diseaseFatty liver diseasePortosystemic pressure gradientChronic liver diseaseLiver diseaseTotal weight lossGastric plicationNoninvasive testsBaseline median body-mass indexMedian body mass indexPercent total weight lossWeight lossProportion of patientsProspective pilot studyBody mass indexLiver stiffness measurementWeight loss proceduresGoal of therapyHepatic decompensationSecondary outcomesPrimary outcomeMass indexPatientsLet-7 suppresses liver fibrosis by inhibiting hepatocyte apoptosis and TGF-β production
Song J, Lv H, Liu B, Hao M, Taylor H, Zhang X, Li D, Huang Y. Let-7 suppresses liver fibrosis by inhibiting hepatocyte apoptosis and TGF-β production. Molecular Metabolism 2023, 78: 101828. PMID: 37898449, PMCID: PMC10641683, DOI: 10.1016/j.molmet.2023.101828.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisFibrosisHepatocytesHumansLiver CirrhosisMiceMicroRNAsTransforming Growth Factor beta1ConceptsFas-mediated apoptosisLet-7Hepatocyte apoptosisNegative feedback loopMouse primary hepatocytesLet-7 miRNAsTGF-b signalingSignaling networksApoptosis of hepatocytesTransient transfectionFas expressionInhibiting hepatocyte apoptosisSiRNA knockdownLet-7 expressionLet-7 overexpressionMouse modelApoptosisPrimary hepatocytesSuppressed hepatocyte apoptosisTET3Liver fibrosisFeedback loopExpressionDriver of liver fibrosisAdeno-associated viral vectors
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