2024
Therapeutic landscape of metabolic dysfunction-associated steatohepatitis (MASH)
Do A, Zahrawi F, Mehal W. Therapeutic landscape of metabolic dysfunction-associated steatohepatitis (MASH). Nature Reviews Drug Discovery 2024, 1-19. PMID: 39609545, DOI: 10.1038/s41573-024-01084-2.Peer-Reviewed Original ResearchSide effect profileTrial end pointsCombination of therapeuticsReverse many aspectsFatty acid synthase inhibitorGenetic susceptibility factorsPlacebo responseEffect profileFibrosis reversalTreated patientsClinical studiesLiver inflammationSynthase inhibitorLiver diseaseTherapeutic approachesClinical useEnd pointsSteatotic liver diseaseTherapeutic landscapeMetabolic environmentHepatocyte deathSusceptibility factorsChronic overnutritionGlobal epidemicLiverCorrigendum to: “A disease-promoting role of the intestinal mycobiome in non-alcoholic fatty liver disease” [J Hepatol (2022) 765-767]
Mehal W, Schwabe R. Corrigendum to: “A disease-promoting role of the intestinal mycobiome in non-alcoholic fatty liver disease” [J Hepatol (2022) 765-767]. Journal Of Hepatology 2024 PMID: 39580245, DOI: 10.1016/j.jhep.2024.10.004.Peer-Reviewed Original ResearchCorrigendum to: “From mice to humans: Unravelling the genetic levers of NASH” [J Hepatol (2020) 749-751]
Mehal W. Corrigendum to: “From mice to humans: Unravelling the genetic levers of NASH” [J Hepatol (2020) 749-751]. Journal Of Hepatology 2024 PMID: 39516051, DOI: 10.1016/j.jhep.2024.10.002.Peer-Reviewed Original ResearchCorrigendum to: “A gold mine of information from a deep dive into the liver transcriptome” [J Hepatol (2024) 540-542]
Mehal W. Corrigendum to: “A gold mine of information from a deep dive into the liver transcriptome” [J Hepatol (2024) 540-542]. Journal Of Hepatology 2024 PMID: 39443197, DOI: 10.1016/j.jhep.2024.10.003.Peer-Reviewed Original ResearchGlucagon promotes increased hepatic mitochondrial oxidation and pyruvate carboxylase flux in humans with fatty liver disease
Petersen K, Dufour S, Mehal W, Shulman G. Glucagon promotes increased hepatic mitochondrial oxidation and pyruvate carboxylase flux in humans with fatty liver disease. Cell Metabolism 2024, 36: 2359-2366.e3. PMID: 39197461, DOI: 10.1016/j.cmet.2024.07.023.Peer-Reviewed Original ResearchAcute kidney injury in severe alcohol-associated hepatitis treated with anakinra plus zinc or prednisone.
Patidar K, Tu W, Cotter T, Simonetto D, Asgharpour A, Jan M, Tang Q, Yu Y, Li Y, Taiwo M, Thevkar Nagesh P, Dasarathy S, Kamath P, McClain C, Chalasani N, Szabo G, Bataller R, Mitchell M, Mehal W, Nagy L, Shah V, Gawrieh S, Sanyal A. Acute kidney injury in severe alcohol-associated hepatitis treated with anakinra plus zinc or prednisone. Hepatology 2024 PMID: 39028887, DOI: 10.1097/hep.0000000000001019.Peer-Reviewed Original ResearchMultivariable competing-risk analysisCompeting-risk analysisTreatment armsKidney injuryRisk factorsWhite blood cell countMulticenter randomized clinical trialAcute kidney injuryKidney injury biomarkersBaseline risk factorsBlood cell countRandomized clinical trialsAKI developmentClinical factorsPrednisoneFollow-upHepatic encephalopathyArterial pressureClinical trialsDay 7Cell countPatientsTrialsBaselineLower survivalInflammasomes 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, 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 cellsRNA modifications in the progression of liver diseases: from fatty liver to cancer
Li S, Mehal W, Ouyang X. RNA modifications in the progression of liver diseases: from fatty liver to cancer. Science China Life Sciences 2024, 67: 2105-2119. PMID: 38809498, PMCID: PMC11545962, DOI: 10.1007/s11427-023-2494-x.Peer-Reviewed Original ResearchRNA modificationsRNA metabolismRNA speciesNon-alcoholic fatty liver diseaseN1-methyladenosineCellular functionsN6-methyladenosineGene expressionRNANon-alcoholic steatohepatitisFatty liver to non-alcoholic steatohepatitisM6AHepatocellular carcinomaGlobal health concernFatty liver diseaseLiver diseaseM5CHigher risk of metabolic syndromePseudouridineAssociated with higher risk of metabolic syndromePathological conditionsRisk of metabolic syndromeGenes-methyladenosineProgression of liver diseaseThe effect of a fermented soy beverage among patients with localized prostate cancer prior to radical prostatectomy
Lokeshwar S, Ali A, Weiss T, Reynolds J, Shuch B, Ferencz T, Kyriakides T, Mehal W, Brito J, Renzulli J, Leapman M. The effect of a fermented soy beverage among patients with localized prostate cancer prior to radical prostatectomy. BMC Urology 2024, 24: 102. PMID: 38702664, PMCID: PMC11067086, DOI: 10.1186/s12894-024-01483-y.Peer-Reviewed Original ResearchConceptsEnd-of-studyProstate cancerRadical prostatectomyTreatment armsDouble-blind randomized trialProstate cancer characteristicsSurgical margin statusLocalized prostate cancerFACT-P scoresBaseline to end-of-studySerum PSACAPRA scoreGleason scorePSA levelsPlacebo-controlledMedium-chain triglyceridesPrimary endpointIntermediate riskClinical stageMargin statusSerum testosteroneRandomization armFACT-PRisk strataITT analysisComplement 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 proteinA gold mine of information from a deep dive into the liver transcriptome
Mehal W. A gold mine of information from a deep dive into the liver transcriptome. Journal Of Hepatology 2024, 80: 540-542. PMID: 38244846, DOI: 10.1016/j.jhep.2024.01.006.Peer-Reviewed Original ResearchLetter to the Editor: Concerns regarding the use of fatty liver index in studies of lean NAFLD
Zahrawi F, Mehal W. Letter to the Editor: Concerns regarding the use of fatty liver index in studies of lean NAFLD. Hepatology 2024, 79: e129-e129. PMID: 38214551, DOI: 10.1097/hep.0000000000000754.Peer-Reviewed Original Research
2023
S1581 Assessing the Effectiveness of Incorporating Weight Management Treatments Into a Fatty Liver Disease Program
Do A, Ilagan-Ying Y, Deng Y, Banini B, Lim J, Mehal W. S1581 Assessing the Effectiveness of Incorporating Weight Management Treatments Into a Fatty Liver Disease Program. The American Journal Of Gastroenterology 2023, 118: s1193-s1194. DOI: 10.14309/01.ajg.0000955964.73046.7b.Peer-Reviewed Original ResearchBioactive 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 ResearchConceptsChronic 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 lipidsInflammationProgressionMechanisms of liver fibrosis in metabolic syndrome
Mehal W. Mechanisms of liver fibrosis in metabolic syndrome. EGastroenterology 2023, 1: e100015. PMID: 37946713, PMCID: PMC10634657, DOI: 10.1136/egastro-2023-100015.Peer-Reviewed Original ResearchNon-alcoholic steatohepatitisLiver fibrosisMetabolic syndromeHepatic stellate cellsHepatocellular injuryImmune systemHSC transdifferentiationGrowth factorChronic hepatocellular injuryInnate immune cellsMetabolite changesInnate immune systemAdaptive immune systemNASH fibrosisHepatocellular damageAntifibrotic strategiesImmune cellsProfibrotic roleT cellsFree fatty acidsStellate cellsViral infectionFibrosisSyndromeEndothelial cellsHumanized mouse liver reveals endothelial control of essential hepatic metabolic functions
Kaffe E, Roulis M, Zhao J, Qu R, Sefik E, Mirza H, Zhou J, Zheng Y, Charkoftaki G, Vasiliou V, Vatner D, Mehal W, AlcHepNet, Kluger Y, Flavell R. Humanized mouse liver reveals endothelial control of essential hepatic metabolic functions. Cell 2023, 186: 3793-3809.e26. PMID: 37562401, PMCID: PMC10544749, DOI: 10.1016/j.cell.2023.07.017.Peer-Reviewed Original ResearchConceptsMetabolic functionsSpecies-specific interactionsKey metabolic functionsCell-autonomous mechanismsNon-alcoholic fatty liver diseaseMajor metabolic hubNon-parenchymal cellsMetabolic hubHuman hepatocytesMicroenvironmental regulationHuman diseasesHuman-specific aspectsHuman pathologiesHomeostatic processesSpecies mismatchCholesterol uptakeFatty liver diseaseParacrine mannerHuman immuneBile acid conjugationSinusoidal endothelial cellsHepatic metabolic functionMouse liverEndothelial cellsCellsMultiomics identifies metabolic subtypes based on fatty acid degradation allocating personalized treatment in hepatocellular carcinoma
Li B, Li Y, Zhou H, Xu Y, Cao Y, Cheng C, Peng J, Li H, Zhang L, Su K, Xu Z, Hu Y, Lu J, Lu Y, Qian L, Wang Y, Zhang Y, Liu Q, Xie Y, Guo S, Mehal W, Yu D. Multiomics identifies metabolic subtypes based on fatty acid degradation allocating personalized treatment in hepatocellular carcinoma. Hepatology 2023, 79: 289-306. PMID: 37540187, PMCID: PMC10789383, DOI: 10.1097/hep.0000000000000553.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsPatient-derived xenograftsTransarterial chemoembolizationF1 subtypeMolecular classificationAnti-programmed cell death-1 therapyNovel molecular classificationCancer patient therapyCheckpoint inhibitorsBevacizumab treatmentPD-L1Immunosuppressive microenvironmentRNA sequencingPatient cohortHepatocellular carcinomaImmunological characteristicsTherapeutic strategiesPotential respondersPatient therapyYM-155Prognosis predictionPrecision therapySingle-cell RNA sequencingMetabolic subtypesTumor microenvironmentPharmacologic Management of Obesity after Liver Transplantation: A Critical Review.
Zahrawi F, Fathma S, Mehal W, Banini B. Pharmacologic Management of Obesity after Liver Transplantation: A Critical Review. Annals Of Gastroenterology And Digestive Disorders 2023, 6: 17-25. PMID: 38098758, PMCID: PMC10719957.Peer-Reviewed Original ResearchMitochondrial DNA and the STING pathway are required for hepatic stellate cell activation
Arumugam S, Li B, Boodapati S, Nathanson M, Sun B, Ouyang X, Mehal W. Mitochondrial DNA and the STING pathway are required for hepatic stellate cell activation. Hepatology 2023, 78: 1448-1461. PMID: 37013923, PMCID: PMC10804318, DOI: 10.1097/hep.0000000000000388.Peer-Reviewed Original ResearchConceptsVoltage-dependent anion channelBioenergetic capacityMitochondrial DNATranscriptional upregulationCyclic GMP-AMP synthaseGMP-AMP synthaseTranscriptional regulationBioenergetic organellesFunctional mitochondriaMitochondrial membraneExternal mitochondrial membraneAnabolic pathwaysMitochondrial massAnion channelInterferon genesHSC transdifferentiationSubsequent activationCGAS-STINGTransdifferentiationIRF3 pathwayPathwaySTING pathwayGenesMitochondriaQuiescent HSCsNew uses for an old remedy: Digoxin as a potential treatment for steatohepatitis and other disorders
Jamshed F, Dashti F, Ouyang X, Mehal W, Banini B. New uses for an old remedy: Digoxin as a potential treatment for steatohepatitis and other disorders. World Journal Of Gastroenterology 2023, 29: 1824-1837. PMID: 37032732, PMCID: PMC10080697, DOI: 10.3748/wjg.v29.i12.1824.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements