2024
Genetics of liver disease in adults
Konkwo C, Chowdhury S, Vilarinho S. Genetics of liver disease in adults. Hepatology Communications 2024, 8: e0408. PMID: 38551385, PMCID: PMC10984672, DOI: 10.1097/hc9.0000000000000408.Peer-Reviewed Original ResearchConceptsInterpretation of genetic variationNext-generation sequencing technologiesIncorporation of genomic informationSomatic genetic variantsGenomic informationSequencing technologiesHuman genomeLiver diseaseGenetic variationGenetic variantsImprove patient careMonogenic diseasesProtective allelesPersonalized medicinePatient careManagement of patientsChronic liver diseaseContribution of riskHealth problemsAnnual deathsGlobal health problemHepatology practiceGenomeEstimated 2Alleles
2019
Exome Sequencing in Clinical Hepatology
Vilarinho S, Mistry PK. Exome Sequencing in Clinical Hepatology. Hepatology 2019, 70: 2185-2192. PMID: 31222768, PMCID: PMC6885087, DOI: 10.1002/hep.30826.BooksConceptsWhole-exome sequencingClinical diagnosisUtility of WESCare of patientsCongenital chloride diarrheaLiver clinicLiver diseaseClinical hepatologyDefinitive diagnosisNovel genetic disorderPediatric disordersClinical relevanceChloride diarrheaSalt-wasting diseaseExome sequencingDiagnosisGenetic disordersDiseaseDisordersPractice of medicineNumerous studiesDiarrheaPatientsHepatologyClinicClinical 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 aminotransferasesRecessive Mutations in KIF12 Cause High Gamma‐Glutamyltransferase Cholestasis
Aksu A, Das SK, Nelson‐Williams C, Jain D, Hoşnut F, Şahin G, Lifton RP, Vilarinho S. Recessive Mutations in KIF12 Cause High Gamma‐Glutamyltransferase Cholestasis. Hepatology Communications 2019, 3: 471-477. PMID: 30976738, PMCID: PMC6442693, DOI: 10.1002/hep4.1320.Peer-Reviewed Original ResearchLiver diseaseHigh GGTUndiagnosed liver diseaseHomozygous mutationCholestatic liver diseaseUnmet medical needWhole-exome sequencingSame homozygous mutationPediatric hepatologyNeonatal cholestasisRare homozygous mutationUnclear etiologyCholestasisUndiagnosed childrenMedical needUnrelated childrenGermline DNADiseaseMember 12ChildrenConsanguineous unionsOlder siblingsMissense mutationsGGTDamaging mutations
2017
Exome analysis of the evolutionary path of hepatocellular adenoma-carcinoma transition, vascular invasion and brain dissemination
Vilarinho S, Erson-Omay E, Mitchell-Richards K, Cha C, Nelson-Williams C, Harmancı AS, Yasuno K, Günel M, Taddei TH. Exome analysis of the evolutionary path of hepatocellular adenoma-carcinoma transition, vascular invasion and brain dissemination. Journal Of Hepatology 2017, 67: 186-191. PMID: 28323122, PMCID: PMC5497691, DOI: 10.1016/j.jhep.2017.03.009.Peer-Reviewed Original ResearchConceptsAdenoma-carcinoma transitionHepatocellular adenomaBrain metastasesHepatocellular carcinomaVascular invasionTumor thrombusCatenin beta 1Rare benign liver tumorMultifocal hepatic lesionsAcute abdominal painBenign liver tumorsPeripheral blood leucocytesSomatic mutationsWhole-exome sequencingParaffin-embedded samplesBrain disseminationAbdominal painLeft hepatectomyMajor complicationsLiver diseaseSpontaneous hemorrhageLeft lobeDisease progressionBlood leucocytesLiver tumors
2016
Recurrent 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
2014
Individual 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
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
2010
Neonatal cholestasis: an uncommon presentation of hyperargininemia
Martins E, Silva E, Vilarinho S, Saudubray JM, Vilarinho L. Neonatal cholestasis: an uncommon presentation of hyperargininemia. Journal Of Inherited Metabolic Disease 2010, 33: 503-506. PMID: 21229317, DOI: 10.1007/s10545-010-9263-7.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acids, EssentialArginaseArginineBiomarkersChildChild DevelopmentChild, PreschoolCholestasisDiet, Protein-RestrictedDisease ProgressionEnd Stage Liver DiseaseFemaleGenetic Predisposition to DiseaseHumansHyperargininemiaHypertension, PortalInfantInfant, NewbornLiver Cirrhosis, BiliaryLiver TransplantationNeonatal ScreeningPhenotypeTreatment OutcomeConceptsNeonatal cholestasisLiver diseaseSuccessful orthotopic liver transplantEnd-stage liver diseaseFurther evaluationProgressive biliary cirrhosisInitial clinical presentationOrthotopic liver transplantProgressive spastic paraparesisCholestatic liver diseaseYears of ageMonths of ageRare inborn errorLiver transplantPortal hypertensionBiliary cirrhosisNeurological examinationClinical presentationUncommon presentationInjury patternsSpastic paraparesisUnexplained cholestasisNeonatal presentationDifferential diagnosisFirst presentation