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A randomized, placebo-controlled trial of cenicriviroc for treatment of nonalcoholic steatohepatitis with fibrosis

2018

The aim of this study was to evaluate cenicriviroc (CVC), a dual antagonist of C-C chemokine receptor types 2 and 5, for treatment of nonalcoholic steatohepatitis (NASH) with liver fibrosis. A randomized, double-blind, multinational phase 2b study enrolled subjects with NASH, a nonalcoholic fatty liver disease activity score [NAS] ≥4, and liver fibrosis (stages 1-3, NASH Clinical Research Network) at 81 clinical sites. Subjects (N = 289) were randomly assigned CVC 150 mg or placebo. Primary outcome was ≥2-point improvement in NAS and no worsening of fibrosis at year 1. Key secondary outcomes were: resolution of steatohepatitis and no worsening of fibrosis; improvement in fibrosis by ≥1 stag…

0301 basic medicineLiver CirrhosisMalePlacebo-controlled studyMedical Biochemistry and MetabolomicsGastroenterologyOral and gastrointestinallaw.inventionHepatitisNASH NAFLD CVC nonalcoholic fatty liver inflammationSteatohepatitis/Metabolic Liver Disease0302 clinical medicineRandomized controlled trialFibrosislawNon-alcoholic Fatty Liver DiseaseNonalcoholic fatty liver diseaseeducation.field_of_studyCVCLiver DiseaseNASHImidazolesMiddle AgedTreatment OutcomeTolerabilityLiverSulfoxides6.1 PharmaceuticalsCCR5 Receptor Antagonists030211 gastroenterology & hepatologyOriginal ArticleFemalePatient SafetyAdultmedicine.medical_specialtyPopulationChronic Liver Disease and CirrhosisClinical Trials and Supportive ActivitiesClinical SciencesImmunologyPlacebo03 medical and health sciencesDouble-Blind MethodClinical ResearchInternal medicineNAFLDmedicinenonalcoholic fatty liverHumanseducationAgedHepatologyGastroenterology & Hepatologybusiness.industryEvaluation of treatments and therapeutic interventionsOriginal Articlesmedicine.diseaseequipment and suppliesSurgeryCVC; NAFLD; NASH; inflammation; nonalcoholic fatty liver030104 developmental biologyinflammationHuman medicineSteatohepatitisbusinessDigestive DiseasesBiomarkers
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Elafibranor, an Agonist of the Peroxisome Proliferator-Activated Receptor-alpha and -delta, Induces Resolution of Nonalcoholic Steatohepatitis Withou…

2016

International audience; BACKGROUND & AIMS: Elafibranor is an agonist of the peroxisome proliferator-activated receptor-α and peroxisome proliferator-activated receptor-δ. Elafibranor improves insulin sensitivity, glucose homeostasis, and lipid metabolism and reduces inflammation. We assessed the safety and efficacy of elafibranor in an international, randomized, double-blind placebo-controlled trial of patients with nonalcoholic steatohepatitis (NASH).METHODS: Patients with NASH without cirrhosis were randomly assigned to groups given elafibranor 80 mg (n = 93), elafibranor 120 mg (n = 91), or placebo (n = 92) each day for 52 weeks at sites in Europe and the United States. Clinical and …

0301 basic medicineLiver CirrhosisMaleTime FactorsIntention to Treat Analysi[SDV]Life Sciences [q-bio]BiopsyPLACEBO-CONTROLLED TRIALTHERAPYGastroenterologySeverity of Illness IndexChalcone0302 clinical medicineChalconesNon-alcoholic Fatty Liver DiseaseGastrointestinal AgentNonalcoholic fatty liver diseasePropionateMedicine and Health SciencesOdds RatioMedicineGlucose homeostasisVITAMIN-Eeducation.field_of_studyGastrointestinal agentFatty liverRemission InductionGastroenterologyMiddle Aged3. Good healthIntention to Treat AnalysisPPARDEuropeTreatment OutcomeLiverACIDPIOGLITAZONE030211 gastroenterology & hepatologyFemalePPARAHumanSignal TransductionAdultCLINICAL-OUTCOMESmedicine.medical_specialtyLogistic ModelTime FactorLiver CirrhosiPopulationfatty liver; NAFLD; PPARA; PPARD; Adult; Biomarkers; Biopsy; Chalcones; Double-Blind Method; Europe; Female; Gastrointestinal Agents; Humans; Intention to Treat Analysis; Liver; Liver Cirrhosis; Logistic Models; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Odds Ratio; PPAR alpha; PPAR gamma; Propionates; Remission Induction; Severity of Illness Index; Signal Transduction; Time Factors; Treatment Outcome; United States; GastroenterologyPlacebo03 medical and health sciencesDouble-Blind MethodGastrointestinal AgentsInternal medicineNAFLDHumansPPAR alphaeducationFATTY LIVER-DISEASEfatty liverHepatologybusiness.industryBiomarkerAMERICAN ASSOCIATIONOdds ratiomedicine.diseaseConfidence intervalUnited StatesPPAR gammaRenal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11]030104 developmental biologyEndocrinologyLogistic ModelsHuman medicinePropionatesbusinessBiomarkers
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Impact of virus eradication in patients with compensated hepatitis C virus-related cirrhosis: competing risks and multistate model

2016

BACKGROUND & AIMS No published study to date has provided a careful analysis of the effects of a sustained viral response (SVR) on the outcomes of patients with compensated hepatitis C virus (HCV)-related cirrhosis in relation to the degree of portal hypertension. Therefore, we estimated the impact of achieving SVR on disease progression, hepatocellular carcinoma (HCC) development and mortality in a large cohort of HCV patients with cirrhosis with or without oesophageal varices (OVs) at the start of antiviral therapy. METHODS A total of 535 Caucasian patients were prospectively recruited to this study. All patients had a clinical or histological diagnosis of compensated HCV-related cirrhosi…

0301 basic medicineLiver CirrhosisMalemedicine.medical_specialtyCirrhosisCarcinoma HepatocellularSVRSustained Virologic ResponseHepatitis C virusHepacivirusmedicine.disease_causeEsophageal and Gastric VaricesGastroenterologyAntiviral Agents03 medical and health sciencesLiver diseasemultistate0302 clinical medicineInternal medicinemedicineHumansProspective StudiesAgedCirrhosiHepatologybusiness.industryLiver Neoplasmsvirus diseasesHepatitis CHepatitis C ChronicMiddle Agedmedicine.diseasedigestive system diseases030104 developmental biologyItalyLiverHepatocellular carcinomaHCVDisease Progression030211 gastroenterology & hepatologyFemaleViral hepatitisLiver cancerbusinessViral load
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Refining prediction of survival after TIPS with the novel Freiburg index of post-TIPS survival.

2021

Background & Aims Transjugular intrahepatic portosystemic shunt (TIPS) implantation is an effective and safe treatment for complications of portal hypertension. Survival prediction is important in these patients as they constitute a high-risk population. Therefore, the aim of our study was to develop an alternative prognostic model for accurate survival prediction after planned TIPS implantation. Methods A total of 1,871 patients with de novo TIPS implantation for ascites or secondary prophylaxis of variceal bleeding were recruited retrospectively. The study cohort was divided into a training set (80% of study patients; n = 1,496) and a validation set (20% of study patients; n = 375). Furth…

0301 basic medicineLiver CirrhosisMalemedicine.medical_specialtyCirrhosismedicine.medical_treatmentPopulationClinical Decision-MakingSerum Albumin HumanEsophageal and Gastric Varices03 medical and health sciences0302 clinical medicineRisk FactorsInternal medicineAscitesmedicineSecondary PreventionHumanseducationAgedRetrospective Studieseducation.field_of_studyFramingham Risk ScoreHepatologyProportional hazards modelbusiness.industryAge FactorsAscitesBilirubinMiddle Agedmedicine.diseasePrognosisSurvival Rate030104 developmental biologyTreatment OutcomeResearch DesignCreatinineCohortPortal hypertension030211 gastroenterology & hepatologyFemalemedicine.symptomPortasystemic Shunt Transjugular IntrahepaticbusinessGastrointestinal HemorrhageTransjugular intrahepatic portosystemic shuntJournal of hepatology
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TM6SF2 rs58542926 is not associated with steatosis and fibrosis in largecohort of patients with genotype 1 chronic hepatitis C

2016

Background & Aims We tested the putative association of the rs58542926 variant of TM6SF2, a recently described genetic determinant of nonalcoholic fatty liver disease, with steatosis and fibrosis in genotype 1(G1) chronic hepatitis C(CHC) patients. Methods A total of 694 consecutively biopsied Caucasian G1 CHC patients were genotyped for TM6SF2 rs58542926, IL28B rs12979860 and PNPLA3 rs738409. Steatosis was classified as absent (<5%), mild-moderate(5–29%) and severe(≥30%), Fibrosis was considered severe if=F3-F4. Results Carriers of TM6SF2 rs58542926 (6.3% of patients) exhibited lower serum levels of cholesterol (P = 0.04) and triglycerides (P = 0.01), but a similar distribution of steatosi…

0301 basic medicineLiver CirrhosisMalesteatosiIL28BStatistics as TopicGastroenterologySeverity of Illness IndexCohort Studies0302 clinical medicineFibrosisNon-alcoholic Fatty Liver DiseaseNonalcoholic fatty liver diseaseMembrane ProteinFatty liverHepatitis CMiddle AgedItalyLiver030211 gastroenterology & hepatologyFemaleHumanAdultmedicine.medical_specialtyLiver Cirrhosisteatosis; CHC; IL28B; PNPLA3; TM6SF2; Adult; Cohort Studies; Female; Hepatitis C Chronic; Humans; Interleukins; Italy; Lipase; Liver; Male; Membrane Proteins; Middle Aged; Severity of Illness Index; Statistics as Topic; Fatty Liver; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease; HepatologyTM6SF203 medical and health sciencesInternal medicineSeverity of illnessmedicineHumansPNPLA3Hepatologybusiness.industryInterleukinsMembrane ProteinsOdds ratioLipaseHepatologyHepatitis C ChronicInterleukinmedicine.diseaseFatty LiverCHC030104 developmental biologyEndocrinologyInterferonsSteatosisCohort Studiebusiness
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Prevalence and severity of nonalcoholic fatty liver disease by transient elastography: Genetic and metabolic risk factors in a general population.

2017

BACKGROUND & AIMS The worldwide spread of obesity is leading to a dramatic increase in the prevalence of nonalcoholic fatty liver disease (NAFLD) and its complications. We aimed to evaluate both prevalence and factors associated with NAFLD in a general population in a Mediterranean area. METHODS We considered 890 consecutive individuals included in the community-based ABCD (Alimentazione, Benessere Cardiovascolare e Diabete) study (ISRCTN15840340). Controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) were measured with FibroScan. Participants were genotyped for PNPLA3 rs738409 and TM6SF2 rs58542926 variants. RESULTS The prevalence of NAFLD in the cohort was 48%. NAFL…

0301 basic medicineLiver CirrhosisMalesteatosigeneral populationGastroenterologySeverity of Illness Index0302 clinical medicinepatatin like phospholipase domain containing 3FibrosisNon-alcoholic Fatty Liver DiseaseRisk FactorsNonalcoholic fatty liver diseasePrevalenceliver stiffness measurementeducation.field_of_studyMiddle Agedtransient elastographycontrolled attenuation parameterItalyLiverCohortElasticity Imaging Techniquestransmembrane 6 superfamily 2030211 gastroenterology & hepatologyFemalefibrosiAdultmedicine.medical_specialtyPopulationPopulationPolymorphism Single Nucleotide03 medical and health sciencesDiabetes mellitusInternal medicinemedicineDiabetes MellitusHumansObesityeducationstiffneAgedHepatologybusiness.industrynutritional and metabolic diseasesMembrane ProteinsLipasemedicine.diseaseObesitydigestive system diseases030104 developmental biologyLogistic ModelsTransient elastographybusinessTM6SF2Liver international : official journal of the International Association for the Study of the Liver
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The rs11187533 C&amp;#x3e;T Variant of the &lt;b&gt;&lt;i&gt;FFAR4&lt;/i&gt;&lt;/b&gt; Gene Is Associated with Lower Levels of Fasting Glucose and De…

2020

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Genetic factors can modulate the development of associated comorbidities in obesity. It has been shown that loss-of-function variants of the &lt;i&gt;free fatty acid receptor 4 (FFAR4)&lt;/i&gt; gene negatively affect obesity comorbidities such as insulin resistance and fatty liver disease. &lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; To test the relationships of metabolic factors in children with obesity with variants of the &lt;i&gt;FFAR4&lt;/i&gt; gene. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; We performed an association study of 3 single nucleotide polymorphisms (SNPs) of &lt;i&gt;FFAR4&lt;/i&gt; (rs10882273 T&amp;#x3e;C, rs1…

0301 basic medicineLiver injurymedicine.medical_specialty030109 nutrition & dieteticsNutrition and Dieteticsbusiness.industryFatty liverMedicine (miscellaneous)030209 endocrinology & metabolismSingle-nucleotide polymorphismmedicine.diseaseObesityMinor allele frequency03 medical and health sciences0302 clinical medicineInsulin resistanceEndocrinologyInternal medicineGenotypemedicineSNPbusinessAnnals of Nutrition and Metabolism
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Biallelic variants in LARS2 and KARS cause deafness and (ovario)leukodystrophy

2019

Supplemental Digital Content is available in the text.

0301 basic medicineLysine-tRNA LigaseMalePathologyMagnetic Resonance SpectroscopyMedizinmembrane proteins030204 cardiovascular system & hematologyMitochondrionDeafnessmedicine.disease_causeCompound heterozygosityCorrectionsLeukoencephalopathyMyelin0302 clinical medicineCytosolLeukoencephalopathies030212 general & internal medicineOvarian DiseasesTransfer RNA AminoacylationChildZebrafishMUTATIONExome sequencing10012MutationBrainMetabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6]General MedicineMiddle AgedDisorders of movement Donders Center for Medical Neuroscience [Radboudumc 3]Magnetic Resonance ImagingMitochondriaProtein Transportendoplasmic reticulummedicine.anatomical_structureChild PreschoolTransfer RNAComputingMethodologies_DOCUMENTANDTEXTPROCESSING/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]Biological AssayFemaleWRBRare cancers Radboud Institute for Health Sciences [Radboudumc 9]Adultcardiomyopathiesmedicine.medical_specialtyMitochondrial diseaseAminoacylationMuscle disorderBiologyArticleMEDIATES INSERTIONAmino Acyl-tRNA Synthetases03 medical and health sciencesSDG 3 - Good Health and Well-beingmedicineAnimalsPoint MutationHumansAmino Acid SequenceAlleleAllelesCOMPLEXGenetic heterogeneitybusiness.industryArsenite Transporting ATPasesLeukodystrophyGenetic Variation10090Original ArticlesZebrafish Proteinsbiology.organism_classificationDILATED CARDIOMYOPATHYmedicine.diseasezebrafishGENEMolecular biologyDisease Models Animal030104 developmental biologyMembrane protein[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics10084Neurology (clinical)Transfer RNA AminoacylationMEMBRANEbusinessSequence Alignment030217 neurology & neurosurgeryexomeNeurology
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Arrestin-β-1 Physically Scaffolds TSH and IGF1 Receptors to Enable Crosstalk

2019

Endogenously expressed TSH receptors (TSHRs) on orbital fibroblasts of patients with Graves ophthalmopathy (GO) use crosstalk with IGF1 receptors (IGF1R) to synergistically stimulate secretion of hyaluronan (HA), a major component of GO pathology. We previously showed crosstalk occurred upstream of mitogen-activated protein kinase (ERK) phosphorylation. Because other G protein-coupled receptors engage arrestin-β-1 (ARRB1) and ERK, we tested whether ARRB1 was a necessary component of TSHR/IGF1R crosstalk. HA secretion was stimulated by the TSHR-stimulating monoclonal antibodies M22 and KSAb1, or immunoglobulins from patients with GO (GO-Igs). Treatment with M22, as previously shown, resulted…

0301 basic medicineMAPK/ERK pathwaymedicine.medical_specialty030209 endocrinology & metabolismStimulationReceptor tyrosine kinaseCell LineReceptor IGF Type 103 medical and health sciencesMice0302 clinical medicineEndocrinologyInternal medicinemedicineArrestinAnimalsHumansPhosphorylationProtein kinase AReceptorResearch ArticlesbiologyChemistryReceptors Thyrotropinbody regionsGraves OphthalmopathyCrosstalk (biology)030104 developmental biologyEndocrinologybeta-Arrestin 1Thyroid Epithelial CellsGene Knockdown Techniquesbiology.proteinPhosphorylationSignal Transduction
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AMPK phosphorylation modulates pain by activation of NLRP3 inflammasome

2016

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0301 basic medicineMESH : Carrier Proteins/geneticsMaleMESH: Fibromyalgia/geneticsFibromyalgiaIndolesPhysiologyInflammasomesClinical BiochemistryInterleukin-1betaInjuryAMP-Activated Protein KinasesNeuropathic painBiochemistryPyrin domainMice0302 clinical medicineAMP-activated protein kinaseRestrictionSunitinibDiseasePhosphorylationGeneral Environmental Sciencebiologyintegumentary systemChemistryInterleukin-18InflammasomePain Perception[SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism[ SDV.MHEP.EM ] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolismMiddle AgedMetforminCell biologyOriginal Research CommunicationsMESH : Fibromyalgia/geneticsHyperalgesiaPhosphorylationFemalemedicine.symptommedicine.drugMESH : Inflammasomes/metabolismAdultmedicine.medical_specialtyPain03 medical and health sciencesMESH: Carrier Proteins/geneticsInternal medicineNLR Family Pyrin Domain-Containing 3 ProteinmedicineAnimalsHumans[SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular BiologyPyrrolesProtein kinase AMolecular Biology[ SDV.BBM ] Life Sciences [q-bio]/Biochemistry Molecular BiologyMESH: Inflammasomes/metabolismFibromialgia patientsAMPK ; fibromyalgia ; NLRP3 InflammasomeDangerAMPKCell BiologyAdenosineMESH: AMP-Activated Protein Kinases/genetics030104 developmental biologyEndocrinologyMetabolismProtein-Kinase AMPKbiology.proteinGeneral Earth and Planetary SciencesMESH : AMP-Activated Protein Kinases/geneticsAnalgesiaCarrier Proteins030217 neurology & neurosurgery
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