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 metabolismGenesGenetics 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 2AllelesAuthor Correction: GIMAP5 deficiency reveals a mammalian ceramide-driven longevity assurance pathway
Park A, Leney-Greene M, Lynberg M, Gabrielski J, Xu X, Schwarz B, Zheng L, Balasubramaniyam A, Ham H, Chao B, Zhang Y, Matthews H, Cui J, Yao Y, Kubo S, Chanchu J, Morawski A, Cook S, Jiang P, Ravell J, Cheng Y, George A, Faruqi A, Pagalilauan A, Bergerson J, Ganesan S, Chauvin S, Aluri J, Edwards-Hicks J, Bohrnsen E, Tippett C, Omar H, Xu L, Butcher G, Pascall J, Karakoc-Aydiner E, Kiykim A, Maecker H, Tezcan İ, Esenboga S, Heredia R, Akata D, Tekin S, Kara A, Kuloglu Z, Unal E, Kendirli T, Dogu F, Karabiber E, Atkinson T, Cochet C, Filhol O, Bosio C, Davis M, Lifton R, Pearce E, Daumke O, Aytekin C, Şahin G, Aksu A, Uzel G, Koneti Rao V, Sari S, Dalgıç B, Boztug K, Cagdas D, Haskologlu S, Ikinciogullari A, Schwefel D, Vilarinho S, Baris S, Ozen A, Su H, Lenardo M. Author Correction: GIMAP5 deficiency reveals a mammalian ceramide-driven longevity assurance pathway. Nature Immunology 2024, 25: 717-717. PMID: 38347083, DOI: 10.1038/s41590-024-01779-z.Peer-Reviewed Original ResearchGIMAP5 deficiency reveals a mammalian ceramide-driven longevity assurance pathway
Park A, Leney-Greene M, Lynberg M, Gabrielski J, Xu X, Schwarz B, Zheng L, Balasubramaniyam A, Ham H, Chao B, Zhang Y, Matthews H, Cui J, Yao Y, Kubo S, Chanchu J, Morawski A, Cook S, Jiang P, Ravell J, Cheng Y, George A, Faruqi A, Pagalilauan A, Bergerson J, Ganesan S, Chauvin S, Aluri J, Edwards-Hicks J, Bohrnsen E, Tippett C, Omar H, Xu L, Butcher G, Pascall J, Karakoc-Aydiner E, Kiykim A, Maecker H, Tezcan İ, Esenboga S, Heredia R, Akata D, Tekin S, Kara A, Kuloglu Z, Unal E, Kendirli T, Dogu F, Karabiber E, Atkinson T, Cochet C, Filhol O, Bosio C, Davis M, Lifton R, Pearce E, Daumke O, Aytekin C, Şahin G, Aksu A, Uzel G, Koneti Rao V, Sari S, Dalgıç B, Boztug K, Cagdas D, Haskologlu S, Ikinciogullari A, Schwefel D, Vilarinho S, Baris S, Ozen A, Su H, Lenardo M. GIMAP5 deficiency reveals a mammalian ceramide-driven longevity assurance pathway. Nature Immunology 2024, 25: 282-293. PMID: 38172257, PMCID: PMC11151279, DOI: 10.1038/s41590-023-01691-y.Peer-Reviewed Original Research
2022
Fulminant Viral Hepatitis in Two Siblings with Inherited IL-10RB Deficiency
Korol C, Belkaya S, Alsohime F, Lorenzo L, Boisson-Dupuis S, Brancale J, Neehus A, Vilarinho S, Zobaida A, Halwani R, Al-Muhsen S, Casanova J, Jouanguy E. Fulminant Viral Hepatitis in Two Siblings with Inherited IL-10RB Deficiency. Journal Of Clinical Immunology 2022, 43: 406-420. PMID: 36308662, PMCID: PMC9892130, DOI: 10.1007/s10875-022-01376-5.Peer-Reviewed Original ResearchConceptsEarly onset inflammatory bowel diseaseFulminant viral hepatitisHepatitis A virusIL-10IL-22IL-26Viral hepatitisIFN-λ1Inflammatory bowel diseaseIFN-γ productionIFN-γ activityLife-threatening diseaseImpairs cellular responsesHAV infectionBowel diseaseLymphocyte cytotoxicityIL-18BPIFN-λsDisease-causing variantsHealthy individualsPatientsA virusCellular responsesUnrelated patientsPotent antagonist
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 studiesDiarrheaPatientsHepatologyClinicReply to: “Whole exome sequencing for personalized hepatology: Expanding applications in adults and challenges”
Hakim A, Mistry PK, Vilarinho S. Reply to: “Whole exome sequencing for personalized hepatology: Expanding applications in adults and challenges”. Journal Of Hepatology 2019, 71: 850-851. PMID: 31378425, DOI: 10.1016/j.jhep.2019.07.005.Peer-Reviewed Case Reports and Technical NotesClinical 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 mutationsMitoMatters 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
2018
Great Expectations: Principal Investigator and Trainee Perspectives on Hiring, Supervision, and Mentoring
Kaps L, Stine JG, Mellinger J, Vilarinho S. Great Expectations: Principal Investigator and Trainee Perspectives on Hiring, Supervision, and Mentoring. Hepatology Communications 2018, 2: 999-1004. PMID: 30248677, PMCID: PMC6128226, DOI: 10.1002/hep4.1205.Commentaries, Editorials and LettersPrototheca zopfii Colitis in Inherited CARD9 Deficiency
Sari S, Dalgic B, Muehlenbachs A, DeLeon-Carnes M, Goldsmith CS, Ekinci O, Jain D, Keating MK, Vilarinho S. Prototheca zopfii Colitis in Inherited CARD9 Deficiency. The Journal Of Infectious Diseases 2018, 218: 485-489. PMID: 29659908, PMCID: PMC6049027, DOI: 10.1093/infdis/jiy198.Peer-Reviewed Original ResearchConceptsCARD9 deficiencyInherited CARD9 DeficiencySpecific immune defectsAbdominal painImmune defectsBloody diarrheaImmunocompromised individualsExome sequencingHuman protothecosisConsanguineous unionsProtothecosisNew mechanistic insightsFrameshift mutationDeficiencyPancolitisColitisPainDiarrheaPatientsPrototheca zopfiiImmunodeficiencyCARD9InfectionImmunityMonths
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
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 acidsFibrosisAtaxiaLiverPioneering a Global Cure for Chronic Hepatitis C Virus Infection
Vilarinho S, Lifton RP. Pioneering a Global Cure for Chronic Hepatitis C Virus Infection. Cell 2016, 167: 12-15. PMID: 27634325, DOI: 10.1016/j.cell.2016.08.038.BooksRecurrent 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 useThe Role of ARF6 in Biliary Atresia
Ningappa M, So J, Glessner J, Ashokkumar C, Ranganathan S, Min J, Higgs BW, Sun Q, Haberman K, Schmitt L, Vilarinho S, Mistry PK, Vockley G, Dhawan A, Gittes GK, Hakonarson H, Jaffe R, Subramaniam S, Shin D, Sindhi R. The Role of ARF6 in Biliary Atresia. PLOS ONE 2015, 10: e0138381. PMID: 26379158, PMCID: PMC4574480, DOI: 10.1371/journal.pone.0138381.Peer-Reviewed Original ResearchTherapeutic Strategies for Hepatocellular Carcinoma: New Advances and Challenges
Vilarinho S, Taddei T. Therapeutic Strategies for Hepatocellular Carcinoma: New Advances and Challenges. Current Treatment Options In Gastroenterology 2015, 13: 219-234. PMID: 25791207, DOI: 10.1007/s11938-015-0049-8.BooksLiver transplantationSurgical resectionTherapeutic modalitiesContrast-enhanced computerized tomographyBi-lobar diseaseDecompensated liver diseaseOpinion statementHepatocellular carcinomaPortal venous washoutCatheter-directed therapyCurative surgical resectionGood performance statusLiver synthetic functionYttrium-90 microspheresPortal vein occlusionExtra-hepatic metastasisNon-cirrhotic liverHigh-risk individualsInternal radiation therapyMultiple therapeutic modalitiesDiagnosis of HCCMagnetic resonance imagingLevel of suspicionCurative ablationUnresectable diseaseVenous washout
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 Letters