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showing 10 items of 1548 documents

MBOAT7 rs641738 variant and hepatocellular carcinoma in non-cirrhotic individuals

2017

AbstractNonalcoholic fatty liver disease (NAFLD) represents an emerging cause of hepatocellular carcinoma (HCC), especially in non-cirrhotic individuals. The rs641738 C > T MBOAT7/TMC4 variant predisposes to progressive NAFLD, but the impact on hepatic carcinogenesis is unknown. In Italian NAFLD patients, the rs641738 T allele was associated with NAFLD-HCC (OR 1.65, 1.08–2.55; n = 765), particularly in those without advanced fibrosis (p < 0.001). The risk T allele was linked to 3’-UTR variation in MBOAT7 and to reduced MBOAT7 expression in patients without severe fibrosis. The number of PNPLA3, TM6SF2, and MBOAT7 risk variants was associated with NAFLD-HCC independently of clinical fa…

0301 basic medicineLiver CirrhosisMaleAlcoholic liver diseasePathologyCirrhosisliver diseasesGastroenterology0302 clinical medicineSettore BIO/13 - Biologia ApplicataNon-alcoholic Fatty Liver DiseaseRisk FactorsNonalcoholic fatty liver diseasefatty liver-disease; cirrhosis; liver cancer; hepatitis C; hepatocellular carcinoma; liver diseases; fibrosis; carcinogenesis; fatty liver; allelesHCCProspective cohort studySettore MED/12 - GastroenterologiaMultidisciplinaryLiver NeoplasmsQRhepatocellular carcinomaSingle NucleotideMiddle Aged3. Good healthItalyfatty liver-diseaseHepatocellular carcinomaCohortMedicine030211 gastroenterology & hepatologyFemalecarcinogenesisAcyltransferases; Adult; Aged; Carcinoma Hepatocellular; Female; Gene Expression Regulation; Genotype; Humans; Italy; Liver Cirrhosis; Liver Neoplasms; Male; Membrane Proteins; Middle Aged; Non-alcoholic Fatty Liver Disease; Polymorphism Single Nucleotide; Risk Factors; Alleles; Genetic Association Studies; Genetic Predisposition to Disease; Genetic VariationAdultmedicine.medical_specialtyCarcinoma HepatocellularGenotypeSciencePolymorphism Single NucleotideArticleliver cancer03 medical and health sciencesInternal medicinemedicineHumansGenetic Predisposition to DiseaseAllelePolymorphismAllelesGenetic Association Studiesfatty liverAgedSettore MED/06 - ONCOLOGIA MEDICAbusiness.industrycirrhosisfibrosisCarcinomaGenetic VariationMembrane ProteinsHepatocellularmedicine.diseasedigestive system diseases030104 developmental biologyGene Expression Regulationhepatitis CbusinessAcyltransferasesTM6SF2Scientific Reports
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Decreasing role of HCV and HBV infections as aetiological factors of hepatocellular carcinoma in Italy

2019

Background: The epidemiology of hepatocellular carcinoma (HCC) is characterized by a dynamical temporal trend of well-established and emerging risk factors. Methods: We evaluated the temporal trend of aetiological factors of HCC over the last two decades in Italy. HCC cases were recruited from two previously published national studies in 1996 and in 2008 and HCC cases were also enlisted from two national surveys in 2001 and in 2014 enrolling consecutive subjects with chronic liver disease (CLD) referring to more than 80 liver units scattered all over the country for a 6-monthperiod. Results: Out of the 9997 subjects with CLD recruited in 2001 and the 2408 recruited in 2014, 3.3% and 5.7% (P…

0301 basic medicineLiver CirrhosisMaleHepatocellular carcinomaPrevalenceHepacivirusSex FactorChronic liver diseaseAntibodies ViralGastroenterology0302 clinical medicineRisk FactorsSurveys and QuestionnairesHBVPrevalenceMedicineAge Factor030212 general & internal medicineProspective Studieseducation.field_of_studyIncidence (epidemiology)IncidenceLiver NeoplasmsAge FactorsGeneral MedicineHepatitis CHepatitis B viruHepatitis BMiddle AgedHepatitis BHepatitis CInfectious DiseasesItalyLiver NeoplasmHepatocellular carcinomaHCVFemaleAlcoholHumanMicrobiology (medical)medicine.medical_specialtyHepatitis B virusCarcinoma HepatocellularLiver Cirrhosi030106 microbiologyPopulation03 medical and health sciencesSex FactorsInternal medicineHumansRisk factoreducationAgedCross-Sectional StudieHepacivirubusiness.industryRisk Factormedicine.diseasedigestive system diseasesProspective StudieCross-Sectional Studiesbusiness
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Modeling of Hepatocytes Proliferation Isolated from Proximal and Distal Zones from Human Hepatocellular Carcinoma Lesion

2016

Isolation of hepatocytes from cirrhotic human livers and subsequent primary culture are important new tools for laboratory research and cell-based therapeutics in the study of hepatocellular carcinoma (HCC). Using such techniques, we have previously identified different subpopulations of human hepatocytes and among them one is showing a progressive transformation of hepatocytes in HCC-like cells. We have hypothesized that increasing the distance from the neoplastic lesion might affect hepatocyte function and transformation capacity. However, limited information is available in comparing the growth and proliferation of human hepatocytes obtained from different areas of the same cirrhotic liv…

0301 basic medicineLiver CirrhosisMalePathologyCirrhosislcsh:MedicinePathology and Laboratory Medicine0302 clinical medicineAnimal CellsMedicine and Health SciencesTumor Cells Culturedlcsh:ScienceMultidisciplinaryLiver DiseasesFatty liverLiver NeoplasmsMiddle AgedLiverCirrhosisOncologyCell Processes030220 oncology & carcinogenesisHepatocellular carcinomaLiver FibrosisFemalemedicine.symptomCellular TypesAnatomyResearch Articlemedicine.medical_specialtyCarcinoma HepatocellularGastroenterology and HepatologyBiologyResearch and Analysis MethodsCarcinomasCell GrowthLesion03 medical and health sciencesSigns and SymptomsDiagnostic MedicineGastrointestinal TumorsmedicineCarcinomaHumansImmunohistochemistry TechniquesAgedCell ProliferationCell growthlcsh:RBiology and Life SciencesCancers and NeoplasmsCell BiologyHepatocellular Carcinomamedicine.diseaseProliferating cell nuclear antigenFatty LiverHistochemistry and Cytochemistry Techniques030104 developmental biologyCancer cellbiology.proteinHepatocytesImmunologic TechniquesLesionslcsh:QPLoS ONE
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Renin-Angiotensin System Inhibitors, Type 2 Diabetes and Fibrosis Progression: An Observational Study in Patients with Nonalcoholic Fatty Liver Disea…

2016

Background The clinical determinants of fibrosis progression in nonalcoholic fatty liver disease (NAFLD) are still under definition. Aim To assess the clinical determinants of fibrosis progression rate (FPR) in NAFLD patients with baseline and follow-up histological evaluation, with a special focus on the impact of pharmacological therapy. Methods In an observational cohort of 118 Italian patients from tertiary referral centers, liver histology was evaluated according to Kleiner. Independent predictors of FPR were selected by a stepwise regression approach. Results Median follow-up was 36 months (IQR 24–77). Twenty-five patients (18%) showed some amelioration, 63 (53%) had stability, 30 (25…

0301 basic medicineLiver CirrhosisMalePeptide HormonesBiopsyTertiary Care Centerlcsh:MedicineBlood PressureAngiotensin-Converting Enzyme InhibitorsType 2 diabetesGastroenterologyVascular MedicineBiochemistryRenin-Angiotensin SystemTertiary Care Centers0302 clinical medicineFibrosisRetrospective StudieNon-alcoholic Fatty Liver DiseaseNonalcoholic fatty liver diseaseMedicine and Health SciencesEthnicitieslcsh:ScienceDiureticsMultidisciplinarymedicine.diagnostic_testMedicine (all)Liver DiseasesFatty liverAngiotensin Receptor AntagonistMiddle AgedPrognosisMetforminMetforminItalian PeopleItalyLiverHypertensionDisease Progression030211 gastroenterology & hepatologyFemaleAnatomymedicine.drugHumanResearch ArticleAdultmedicine.medical_specialtyHistologyPrognosiLiver CirrhosiAdrenergic beta-AntagonistsSurgical and Invasive Medical ProceduresGastroenterology and HepatologyFollow-Up Studie03 medical and health sciencesAngiotensin Receptor AntagonistsInternal medicineDiabetes mellitusBiopsymedicineDiureticHumansRetrospective StudiesBiochemistry Genetics and Molecular Biology (all)business.industrylcsh:RAdrenergic beta-Antagonistnutritional and metabolic diseasesBiology and Life SciencesRetrospective cohort studyAngiotensin-Converting Enzyme Inhibitormedicine.diseaseFibrosisHormonesFatty Liver030104 developmental biologyEndocrinologyAgricultural and Biological Sciences (all)Diabetes Mellitus Type 2People and Placeslcsh:QPopulation GroupingsHydroxymethylglutaryl-CoA Reductase InhibitorHydroxymethylglutaryl-CoA Reductase InhibitorsbusinessDevelopmental BiologyFollow-Up StudiesPLoS ONE
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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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PI3K inhibition reduces murine and human liver fibrogenesis in precisioncut liver slices

2019

Background: Liver fibrosis results from continuous inflammation and injury. Despite its high prevalence worldwide, no approved antifibrotic therapies exist. Omipalisib is a selective inhibitor of the PI3K/mTOR pathway that controls nutrient metabolism, growth and proliferation. It has shown antifibrotic properties in vitro. While clinical trials for idiopathic pulmonary fibrosis have been initiated, an in-depth preclinical evaluation is lacking. We evaluated omipalisib's effects on fibrogenesis using the ex vivo model of murine and human precision-cut tissue slices (PCTS).Methods: Murine and human liver and jejunum PCTS were incubated with omipalisib up to 10 mu M for 48 h. PI3K pathway act…

0301 basic medicineLiver CirrhosisMalePrecision-cut tissue slicesPROGRESSIONPharmacologyBILIARYBiochemistryPI3KGSK2126458JejunumMicePhosphatidylinositol 3-Kinases0302 clinical medicineAdenosine TriphosphateFibrosisFIBROSIShealth care economics and organizationsPhosphoinositide-3 Kinase InhibitorsSulfonamidesPyridazinesmedicine.anatomical_structureJejunumTARGET030220 oncology & carcinogenesisToxicityQuinolinesPhosphorylationmedicine.symptomATP Binding Cassette Transporter Subfamily BLiver fibrosisEARLY-ONSETInflammation03 medical and health sciencesmedicineAnimalsHumansOmipalisibProtein kinase BPI3K/AKT/mTOR pathwayPharmacologybusiness.industryCUT LIVERmedicine.diseaseMice Inbred C57BLMODEL030104 developmental biologybusinessMATRIXEx vivoBiochemical Pharmacology
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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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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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