2024
Integrative 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 metabolismGenes
2019
Clinical utility of genomic analysis in adults with idiopathic liver disease
Hakim A, Zhang X, DeLisle A, Oral EA, Dykas D, Drzewiecki K, Assis DN, Silveira M, Batisti J, Jain D, Bale A, Mistry PK, Vilarinho S. Clinical utility of genomic analysis in adults with idiopathic liver disease. Journal Of Hepatology 2019, 70: 1214-1221. PMID: 31000363, PMCID: PMC6526061, DOI: 10.1016/j.jhep.2019.01.036.Peer-Reviewed Original ResearchConceptsIdiopathic liver diseaseUnexplained liver diseaseManagement of adultsWhole-exome sequencingLiver diseaseAdult patientsUnknown etiologyHeterozygous variantsUse of WESAmelioration of dyslipidemiaDaily insulin requirementLeptin replacement therapyUtility of WESChronic liver diseaseNon-alcoholic steatohepatitisAcademic health care centerHealth care centersHomozygous pathogenic variantUnrelated adult patientsNon-oncological diseasesDisease preventive measuresInsulin requirementsLean patientsDevastating complicationLiver aminotransferasesMitoMatters Targeted next generation sequencing identifies novel pathogenic variants and provides molecular diagnoses in a cohort of pediatric and adult patients with unexplained mitochondrial dysfunction
Nogueira C, Silva L, Pereira C, Vieira L, Leão Teles E, Rodrigues E, Campos T, Janeiro P, Gaspar A, Dupont J, Bandeira A, Martins E, Magalhães M, Sequeira S, Vieira JP, Santos H, Vilarinho S, Vilarinho L. MitoMatters Targeted next generation sequencing identifies novel pathogenic variants and provides molecular diagnoses in a cohort of pediatric and adult patients with unexplained mitochondrial dysfunction. Mitochondrion 2019, 47: 309-317. PMID: 30831263, DOI: 10.1016/j.mito.2019.02.006.Peer-Reviewed Original ResearchConceptsMitochondrial diseaseWhole mitochondrial genomeNext-generation sequencing strategyMitochondrial genomePathogenic variantsCustom gene panelSequencing strategyMitochondrial dysfunctionMolecular analysisMutational landscapeNGS strategyNovel pathogenic variantsPhenotypic heterogeneityEffective therapeutic optionHigh diagnostic yieldGene panelMolecular diagnosisVariantsAdult patientsGenomeTherapeutic optionsUnknown significanceDiagnostic yield
2016
ACOX2 deficiency: A disorder of bile acid synthesis with transaminase elevation, liver fibrosis, ataxia, and cognitive impairment
Vilarinho S, Sari S, Mazzacuva F, Bilgüvar K, Esendagli-Yilmaz G, Jain D, Akyol G, Dalgiç B, Günel M, Clayton PT, Lifton RP. ACOX2 deficiency: A disorder of bile acid synthesis with transaminase elevation, liver fibrosis, ataxia, and cognitive impairment. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: 11289-11293. PMID: 27647924, PMCID: PMC5056113, DOI: 10.1073/pnas.1613228113.Peer-Reviewed Original ResearchConceptsAcyl-CoA oxidase 2Liver fibrosisCognitive impairmentElevated transaminase levelsTreatable inborn errorsBile acid synthesisBile acid intermediatesBile acid biosynthesisTransaminase elevationTransaminase levelsMarked elevationMild ataxiaBile acidsPatient's liverOxidase 2Acyl-CoA oxidaseOld maleBranched chain acyl-CoA oxidaseInborn errorsExome sequencingPremature termination mutationsBranched-chain fatty acidsFibrosisAtaxiaLiverRecurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension
Vilarinho S, Sari S, Yilmaz G, Stiegler AL, Boggon TJ, Jain D, Akyol G, Dalgic B, Günel M, Lifton RP. Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension. Hepatology 2016, 63: 1977-1986. PMID: 26874653, PMCID: PMC4874872, DOI: 10.1002/hep.28499.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAmino Acid SequenceAnimalsCattleChildChild, PreschoolDNA Mutational AnalysisDogsFemaleGenes, RecessiveHomozygoteHumansHypertension, PortalInfantLiver FailureMaleMolecular Sequence DataPedigreePhosphotransferases (Alcohol Group Acceptor)Principal Component AnalysisRatsYoung AdultConceptsIdiopathic noncirrhotic portal hypertensionNoncirrhotic portal hypertensionPortal hypertensionHuman immunodeficiency viral infectionNoncirrhotic liver diseaseStable portal hypertensionSubset of patientsTreatment of patientsNucleoside analog didanosineLiver failureIndeterminate etiologyLiver diseaseHypertensionKinase levelsNew genetic testsViral infectionMechanisms mediatingDGUOK deficiencyPhenotypic spectrumSpecific causesDeoxyguanosine kinaseExome sequencingPatientsConsanguineous familyFunction mutations
2015
The Impact of Enhanced Screening and Treatment on Hepatitis C in the United States
Durham DP, Skrip LA, Bruce RD, Vilarinho S, Elbasha EH, Galvani AP, Townsend JP. The Impact of Enhanced Screening and Treatment on Hepatitis C in the United States. Clinical Infectious Diseases 2015, 62: 298-304. PMID: 26628566, PMCID: PMC4706637, DOI: 10.1093/cid/civ894.Peer-Reviewed Original ResearchConceptsHepatitis C virusInterferon-free DAAsHCV incidenceTreatment ratesChronic hepatitis C virusCases of cirrhosisInjection drug useImpact of administrationAnnual treatment ratesEnhanced screeningHCV prevalenceHCV screeningDecompensated cirrhosisHCV infectionHCV transmissionHepatitis CLiver transplantActing antiviralsLevels of screeningPatients 4C virusHepatocellular carcinomaEpidemiological dataUniversal screeningDrug use
2014
New advances in precision medicine for hepatocellular carcinoma recurrence prediction and treatment
Vilarinho S, Calvisi DF. New advances in precision medicine for hepatocellular carcinoma recurrence prediction and treatment. Hepatology 2014, 60: 1812-1814. PMID: 25042754, DOI: 10.1002/hep.27311.Commentaries, Editorials and LettersIndividual exome analysis in diagnosis and management of paediatric liver failure of indeterminate aetiology
Vilarinho S, Choi M, Jain D, Malhotra A, Kulkarni S, Pashankar D, Phatak U, Patel M, Bale A, Mane S, Lifton RP, Mistry PK. Individual exome analysis in diagnosis and management of paediatric liver failure of indeterminate aetiology. Journal Of Hepatology 2014, 61: 1056-1063. PMID: 25016221, PMCID: PMC4203706, DOI: 10.1016/j.jhep.2014.06.038.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceBase SequenceCarboxylic Ester HydrolasesChildCholestasisDNA Mutational AnalysisEnd Stage Liver DiseaseExomeFatal OutcomeFemaleGenes, RecessiveHepatolenticular DegenerationHeterozygoteHomozygoteHumansInfant, NewbornLiver FailureLiver Failure, AcuteMaleMembrane ProteinsMitochondrial ProteinsMolecular Sequence DataPedigreeReceptor, Notch2RNA Splice SitesSequence Homology, Amino AcidConceptsFatal acute liver failureWhole-exome sequencingAdvanced liver diseaseAcute liver failureIndeterminate etiologyYear old femaleLiver failureLiver diseaseMetabolic liver diseasePatient 3Treatment optionsPhenotypic spectrumPediatric liver failureDecompensated liver cirrhosisManagement of childrenOptimal treatment optionsAge 3 monthsNovel inborn errorLiver transplantAtypical presentationLiver cirrhosisHepatocerebral mitochondrial DNA depletion syndromePatient 1Patient 2Unknown etiology
2013
New frontier in liver cancer treatment: Oncolytic viral therapy
Vilarinho S, Taddei TH. New frontier in liver cancer treatment: Oncolytic viral therapy. Hepatology 2013, 59: 343-346. PMID: 23836532, PMCID: PMC4427510, DOI: 10.1002/hep.26605.Commentaries, Editorials and Letters
2011
IL-21 is pivotal in determining age-dependent effectiveness of immune responses in a mouse model of human hepatitis B
Publicover J, Goodsell A, Nishimura S, Vilarinho S, Wang ZE, Avanesyan L, Spolski R, Leonard WJ, Cooper S, Baron JL. IL-21 is pivotal in determining age-dependent effectiveness of immune responses in a mouse model of human hepatitis B. Journal Of Clinical Investigation 2011, 121: 1154-1162. PMID: 21393863, PMCID: PMC3049376, DOI: 10.1172/jci44198.Peer-Reviewed Original ResearchConceptsIL-21 productionImmune responseHBV infectionIL-21Viral clearanceYoung miceAdult miceHepatic immune responseAge-dependent outcomesIL-21 receptorB cell responsesAge-dependent effectivenessHuman hepatitis BChronic hepatitisHBV antigensHepatitis BYounger patientsLiver diseaseAntigen persistenceChronic infectionTherapeutic augmentationMajor human pathogenMouse modelBlood samplesAnimal models