Search results for "nonalcoholic fatty liver"

showing 10 items of 142 documents

Application of guidelines for the management of nonalcoholic fatty liver disease in three prospective cohorts of HIV-monoinfected patients

2020

Objectives: Current guidelines recommend use of a diagnostic algorithm to assess disease severity in cases of suspected nonalcoholic fatty liver disease (NAFLD). We applied this algorithm to HIV-monoinfected patients. Methods: We analysed three prospective screening programmes for NAFLD carried out in the following cohorts: the Liver Disease in HIV (LIVEHIV) cohort in Montreal, the Modena HIV Metabolic Clinic (MHMC) cohort and the Liver Pathologies in HIV in Palermo (LHivPa) cohort. In the LIVEHIV and LHivPa cohorts, NAFLD was diagnosed if the controlled attenuation parameter (CAP) was ≥ 248 dB/m; in the MHMC cohort, it was diagnosed if the liver/spleen Hounsfield unit (HU) ratio on abdomin…

0301 basic medicineAdultMalenonalcoholic fatty liver diseasemedicine.medical_specialtyCanadaHIV monoinfection; fibrosis-4; guidelines; nonalcoholic fatty liver disease; specialist referralHIV monoinfectionHIV InfectionsSeverity of Illness Index03 medical and health sciencesLiver disease0302 clinical medicineNon-alcoholic Fatty Liver DiseaseInternal medicineDiabetes mellitusNonalcoholic fatty liver diseasespecialist referralmedicineHumansPharmacology (medical)030212 general & internal medicineProspective Studiesbusiness.industryHealth Policyfibrosis-4Alanine TransaminaseHepatologyMiddle Agedmedicine.disease030112 virologyObesityInfectious DiseasesItalyCohortPractice Guidelines as TopicCoinfectionFemaleGuideline AdherencebusinessViral hepatitisTomography X-Ray ComputedguidelineAlgorithms
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AISF position paper on nonalcoholic fatty liver disease (NAFLD): Updates and future directions

2017

Abstract This review summarizes our current understanding of nonalcoholic fatty liver disease (NAFLD), a multi-factorial systemic disease resulting from a complex interaction between a specific genetic background and multiple environmental/metabolic “hits”. The role of gut microbiota, lipotoxicity, inflammation and their molecular pathways is reviewed in-depth. We also discuss the epidemiology and natural history of NAFLD by pinpointing the remarkably high prevalence of NAFLD worldwide and its inherent systemic complications: hepatic (steatohepatitis, advanced fibrosis and cirrhosis), cardio-metabolic (cardiovascular disease, cardiomyopathy, arrhythmias and type 2 diabetes) and neoplastic (…

0301 basic medicineDiagnostic ImagingLiver Cirrhosismedicine.medical_specialtyCirrhosisEpidemiologySettore MED/12 - GASTROENTEROLOGIAPhysiopathologyNatural historyType 2 diabetesDiseaseDiagnosis; Epidemiology; Genetics; Management; Natural history; PhysiopathologyBioinformaticsGastroenterology03 medical and health sciences0302 clinical medicineGeneticNon-alcoholic Fatty Liver DiseaseInternal medicineNonalcoholic fatty liver diseaseDiagnosismedicineGeneticsHumansmedicine.diagnostic_testHepatologyDiagnosis; Epidemiology; Genetics; Management; Natural history; Physiopathology; Hepatology; Gastroenterologybusiness.industryLiver NeoplasmsGastroenterologyHepatologymedicine.diseaseManagement030104 developmental biologyLipotoxicityDiabetes Mellitus Type 2LiverCardiovascular DiseasesLiver biopsy030211 gastroenterology & hepatologySteatohepatitisbusinessBiomarkersDiagnosi
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Exome-Wide Association Study on Alanine Aminotransferase Identifies Sequence Variants in the GPAM and APOE Associated With Fatty Liver Disease.

2021

BACKGROUND & AIMS: Fatty liver disease (FLD) is a growing epidemic that is expected to be the leading cause of end-stage liver disease within the next decade. Both environmental and genetic factors contribute to the susceptibility of FLD. Several genetic variants contributing to FLD have been identified in exome-wide association studies. However, there is still a missing hereditability indicating that other genetic variants are yet to be discovered. METHODS: To find genes involved in FLD, we first examined the association of missense and nonsense variants with alanine amino transferase at an exome-wide level in 425,671 participants from the UK Biobank. We then validated genetic variants wit…

0301 basic medicineGenome-wide association studyLiver disease0302 clinical medicineENRICHMENT ANALYSISNon-alcoholic Fatty Liver DiseaseRisk FactorsNonalcoholic fatty liver diseaseExomeCONFERS SUSCEPTIBILITYGeneticsINSULIN-RESISTANCEmedicine.diagnostic_testFatty liverGastroenterologyAlanine Transaminase1-Acylglycerol-3-Phosphate O-Acyltransferase3. Good healthGENOMEEuropePhenotypeLiver biopsy030211 gastroenterology & hepatologyNonalcoholic Fatty Liver DiseaseMAFLDSingle-nucleotide polymorphismBiologyTransaminaseRisk Assessment03 medical and health sciencesApolipoproteins ENAFLDmedicineGenetic predispositionHumansGenetic Predisposition to DiseaseHEPATIC STEATOSISGenetic associationMAFLD Phenotype Reproducibility of Results Risk Assessment Risk Factors Transcriptome Genetic Variation Metabolic Associated Fatty Liver Disease Nonalcoholic Fatty Liver Disease Transaminase 1-Acylglycerol-3-Phosphate O-Acyltransferase Alanine Transaminase Apolipoproteins E Biomarkers Europe Exome Gene Expression Profiling Genetic Predisposition to Disease Genome-Wide Association Study Humans Non-alcoholic Fatty Liver DiseaseHepatologyMUTATIONSGene Expression ProfilingGenetic VariationReproducibility of Resultsmedicine.diseaseX-RECEPTORGENE030104 developmental biology3121 General medicine internal medicine and other clinical medicineMetabolic Associated Fatty Liver DiseaseRNA-SEQ DATATranscriptomePATHOGENICITYBiomarkersGenome-Wide Association StudyGastroenterology
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Interferon lambda 4 rs368234815 TT>δG variant is associated with liver damage in patients with nonalcoholic fatty liver disease

2017

Background and Aims: The IFNL3/4 locus influencing innate immunity regulation has been associated with the severity of hepatitis and fibrosis progression during chronic hepatitis C infection, while contrasting results were reported in NAFLD. In this study, we examined whether rs12979860 and the linked causal rs368234815 variant encoding for the alternative IFNL4 protein variant are associated with liver fibrosis and damage in a large multicenter cohort of patients at risk of NASH. To clarify the mechanism, we also evaluated the impact on interferon-stimulated gene (ISG) hepatic expression in a subset of patients. Methods: We considered 946 consecutive Italian individuals at risk of NASH wit…

0301 basic medicineHepatitismedicine.medical_specialtyNAFLD NASH IFNL4Hepatologybusiness.industryLocus (genetics)medicine.diseaseGastroenterology03 medical and health sciences030104 developmental biology0302 clinical medicineFibrosisInternal medicineNonalcoholic fatty liver diseaseCohortGenotypemedicine030211 gastroenterology & hepatologyAllelebusinessProspective cohort studyHepatology
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Investigating fibrosis and inflammation in an ex vivo NASH murine model.

2020

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease, characterized by excess fat accumulation (steatosis). Nonalcoholic steatohepatitis (NASH) develops in 15–20% of NAFLD patients and frequently progresses to liver fibrosis and cirrhosis. We aimed to develop an ex vivo model of inflammation and fibrosis in steatotic murine precision-cut liver slices (PCLS). NASH was induced in C57Bl/6 mice on an amylin and choline-deficient l-amino acid-defined (CDAA) diet. PCLS were prepared from steatohepatitic (sPCLS) and control (cPCLS) livers and cultured for 48 h with LPS, TGFβ1, or elafibranor. Additionally, C57Bl/6 mice were placed on CDAA diet for 12 wk to receive elafibranor…

0301 basic medicineLipopolysaccharidesLiver CirrhosisMalePhysiologyHEPATOCYTESLiver diseaseMice0302 clinical medicineChalconesFibrosisNon-alcoholic Fatty Liver DiseaseNonalcoholic fatty liver diseaseCells CulturedINSULIN-RESISTANCEGastroenterologyElafibranorTGF-BETALiver030211 gastroenterology & hepatologyCHOLINE-DEFICIENT DIETEXPRESSIONmedicine.medical_specialtyEARLY-ONSETIn Vitro TechniquesCollagen Type IProinflammatory cytokineTransforming Growth Factor beta103 medical and health sciencesIn vivoPhysiology (medical)Internal medicinemedicineAnimalsHEPATIC STEATOSISFATTY LIVER-DISEASEInflammationPRECISION-CUT LIVERHepatologybusiness.industrymedicine.diseaseLipid MetabolismDietMice Inbred C57BLDisease Models Animal030104 developmental biologyEndocrinologyPROLIFERATOR-ACTIVATED RECEPTORSSteatosisPropionatesbusinessTranscriptomeEx vivoAmerican journal of physiology. Gastrointestinal and liver physiology
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Transcriptomic profiling across the nonalcoholic fatty liver disease spectrum reveals gene signatures for steatohepatitis and fibrosis

2020

International audience; The mechanisms that drive nonalcoholic fatty liver disease (NAFLD) remain incompletely understood. This large multicenter study characterized the transcriptional changes that occur in liver tissue across the NAFLD spectrum as disease progresses to cirrhosis to identify potential circulating markers. We performed high-throughput RNA sequencing on a discovery cohort comprising histologically characterized NAFLD samples from 206 patients. Unsupervised clustering stratified NAFLD on the basis of disease activity and fibrosis stage with differences in age, aspartate aminotransferase (AST), type 2 diabetes mellitus, and carriage of PNPLA3 rs738409 , a genetic variant assoc…

0301 basic medicineLiver CirrhosisCirrhosis[SDV]Life Sciences [q-bio]DiseaseBiologyTranscriptome03 medical and health sciences0302 clinical medicineFibrosisnashNon-alcoholic Fatty Liver DiseaseDiabetes mellitusNonalcoholic fatty liver diseasemedicineDiabetes MellitusHumansGeneral Medicinemedicine.disease3. Good health030104 developmental biologyDiabetes Mellitus Type 2LiverHumans; Liver; Liver Cirrhosis; Transcriptome; Diabetes Mellitus Type 2; Non-alcoholic Fatty Liver DiseaseImmunology030211 gastroenterology & hepatologyGDF15SteatohepatitisTranscriptomeType 2
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The membrane-bound O-acyltransferase domain-containing 7 variant rs641738 increases inflammation and fibrosis in chronic hepatitis B.

2017

Chronic hepatitis B (CHB) is characterized by hepatic inflammation that promotes progression to cirrhosis and predisposes to the development of hepatocellular carcinoma (HCC). Subtle interindividual genetic variation as well as viral and environmental factors interact to determine disease progression between individuals. Recently, the rs641738 membrane-bound O-acyltransferase domain-containing 7 (MBOAT7) polymorphism was demonstrated to influence histological liver damage in alcoholic liver disease, nonalcoholic fatty liver disease, and hepatitis C, but no data are available for CHB. We evaluated rs641738 influence on disease severity in a cohort of 1,101 patients with CHB. Forty-two patien…

0301 basic medicineLiver CirrhosisMaleAlcoholic liver diseaseCirrhosisSex FactorSeverity of Illness IndexCohort StudiesGene FrequencyFibrosisNon-alcoholic Fatty Liver DiseaseNonalcoholic fatty liver diseaseAge FactorProspective StudiesChronicMembrane ProteinMultivariate AnalysiAge FactorsHepatitis CSingle NucleotideMiddle AgedHepatitis BPrognosisHepatocellular carcinomaDisease ProgressionFemaleHumanAdultmedicine.medical_specialtyLogistic ModelPrognosiAcyltransferaseLiver CirrhosiAcetyltransferases; Acyltransferases; Adult; Age Factors; Cohort Studies; Confidence Intervals; Disease Progression; Female; Gene Frequency; Genetic Predisposition to Disease; Hepatitis B Chronic; Humans; Liver Cirrhosis; Logistic Models; Male; Membrane Proteins; Middle Aged; Multivariate Analysis; Non-alcoholic Fatty Liver Disease; Polymorphism Single Nucleotide; Prognosis; Prospective Studies; Risk Assessment; Severity of Illness Index; Sex FactorsPolymorphism Single NucleotideRisk Assessment03 medical and health sciencesHepatitis B ChronicSex FactorsSDG 3 - Good Health and Well-beingAcetyltransferasesInternal medicineAcetyltransferasemedicineConfidence IntervalsHumansGenetic Predisposition to DiseasePolymorphismHepatologybusiness.industryMembrane ProteinsHepatologymedicine.diseaseMinor allele frequencyProspective Studie030104 developmental biologyLogistic ModelsImmunologyMultivariate AnalysisCohort StudiebusinessConfidence IntervalAcyltransferasesHepatology (Baltimore, Md.)
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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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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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