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Genome-wide Studies Reveal Genetic Risk Factors for Hepatic Fat Content

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Genomics, Proteomics & Bioinformatics 2024年第2期22卷 57-68页

作者： Yanni Li Eline H.van den Berg Alexander Kurilshikov Dasha V.Zhernakova Ranko Gacesa Shixian Hu Esteban A.Lopera-Maya Alexandra Zhernakova Lifelines Cohort Study Vincent E.de Meijer Serena Sanna Robin P.F.Dullaart Hans Blokzijl Eleonora A.M.Festen Jingyuan Fu Rinse K.Weersma Department of Gastroenterology and Hepatology University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands Department of Genetics University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands Department of Gastroenterology and Hepatology Tianjin Medical University General HospitalTianjin Medical UniversityTianjin 300052China Laboratory of Genomic Diversity Center for Computer TechnologiesITMO UniversitySaint Petersburg 199034Russia Institute of Precision Medicine the First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China Department of Surgery Section of Hepatobiliary Surgery and Liver TransplantationUniversity of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands Department of Endocrinology University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands Department of Pediatrics University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands 不详

Genetic susceptibility to metabolic associated fatty liver disease(MAFLD)is complex and poorly *** characterization of the genetic background of hepatic fat content would provide insights into disease etiology and causality of risk *** performed genome-wide association study(GWAS)on two noninvasive definitions of hepatic fat content:magnetic resonance imaging proton density fat fraction(MRI-PDFF)in 16,050 participants and fatty liver index(FLI)in 388,701 participants from the United Kingdom(UK)Biobank(UKBB).Heritability,genetic overlap,and similarity between hepatic fat content phenotypes were analyzed,and replicated in 10,398 participants from the University Medical Center Groningen(UMCG)Genetics Lifelines Initiative(UGLI).Meta-analysis of GWASs of MRI-PDFF in UKBB revealed five statistically significant loci,including two novel genomic loci harboring CREB3L1(rs72910057-T,P=5.40E−09)and GCM1(rs1491489378-T,P=3.16E−09),respectively,as well as three previously reported loci:PNPLA3,TM6SF2,and *** of FLI in UKBB identified 196 genome-wide significant loci,of which 49 were replicated in UGLI,with top signals in ZPR1(P=3.35E−13)and FTO(P=2.11E−09).Statistically significant genetic correlation(rg)between MRI-PDFF(UKBB)and FLI(UGLI)GWAS results was found(rg=0.5276,P=1.45E−03).Novel MRI-PDFF genetic signals(CREB3L1 and GCM1)were replicated in the FLI *** identified two novel genes for MRI-PDFF and 49 replicable loci for *** a difference in hepatic fat content assessment between MRI-PDFF and FLI,a substantial similar genetic architecture was *** is identified as an easy and reliable approach to study hepatic fat content at the population level.

关键词： Hepatic fat content MAFLD Genome-wide association study fatty liver index Magnetic resonance imaging proton density fat fraction

Validity of fatty liver prediction scores for diagnosis of fatty liver by Fibroscan

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 353-360页

作者： Seogsong Jeong Sun Jae Park Seong Kyun Na Sang Min Park Byung-Cheol Song Yun Hwan Oh Department of Biomedical Sciences Seoul National University Graduate SchoolSeoul 03080Korea Department of Biomedical Informatics CHA University School of MedicineCHA UniversitySeongnam 13488Korea Department of Internal Medicine Inje University College of MedicineSeoul 50834Korea Department of Family Medicine Seoul National University HospitalSeoul National University College of MedicineSeoul 03080Korea Department of Internal Medicine Jeju National University HospitalJeju National University College of MedicineJeju 63241Korea Department of Family Medicine Jeju National University HospitalJeju National University College of MedicineJeju 63241Korea Department of Family Medicine Chung-Ang University Gwangmyeong HospitalChung-Ang University College of MedicineGwangmyeong 14353Korea

Background:The Korea National Health and Nutrition Examination Survey nonalcoholic fatty liver disease(K-NAFLD)score was recently developed with the intent to operationally define nonalcoholic fatty liver disease(NAFLD).However,there remained an external validation that confirmed its diagnostic performance,especially in patients with alcohol consumption or hepatitis virus ***:Diagnostic accuracy of the K-NAFLD score was evaluated in a hospital-based cohort consisting of 1388 participants who received Fibroscan®.Multivariate-adjusted logistic regression models and the contrast estimation of receiver operating characteristic curves were used for validation of the K-NAFLD score,fatty liver index(FLI),and hepatic steatosis index(HSI).Results:K-NAFLD-moderate[adjusted odds ratio(aOR)=2.53,95%confidence interval(CI):1.13-5.65]and K-NAFLD-high(aOR=4.14,95%CI:1.69-10.13)groups showed higher risks of fatty liver compared to the K-NAFLD-low group after adjustments for demographic and clinical characteristics,and FLI-moderate and FLI-high groups revealed aORs of 2.05(95%CI:1.22-3.43)and 1.51(95%CI:0.78-2.90),*** addition,the HSI was less predictive for Fibroscan®-defined fatty *** K-NAFLD and FLI also demonstrated high accuracy in the prediction of fatty liver in patients with alcohol consumption and chronic hepatitis virus infection,and the adjusted area under curve values were comparable between K-NAFLD and ***:Externally validation of the K-NAFLD and FLI showed that these scores may be a useful,noninvasive,and non-imaging modality for the identification of fatty *** addition,these scores also predicted fatty liver in patients with alcohol consumption and chronic hepatitis virus infection.

关键词： Nonalcoholic fatty liver disease fatty liver index Hepatic steatosis index

liver Fat Scores for Noninvasive Diagnosis and Monitoring of Nonalcoholic fatty liver Disease in Epidemiological and Clinical Studies

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Journal of Clinical and Translational Hepatology 2023年第5期11卷 1212-1227页

作者： Mona Reinshagen Stefan Kabisch Andreas F.H.Pfeiffer Joachim Spranger Department of Endocrinology and Metabolism Campus Benjamin FranklinCharitéUniversity MedicineBerlinGermany Deutsches Zentrum für Diabetesforschung e.V. Geschäftsstelle am Helmholtz-Zentrum MünchenNeuherbergGermany

Nonalcoholic fatty liver disease(NAFLD)is strongly associated with the metabolic syndrome and type 2 diabetes and independently contributes to long-term *** often asymptomatic but reversible,it would require population-wide screening,but direct diagnostics are either too invasive(liver biopsy),costly(MRI)or depending on the examiner’s expertise(ultrasonography).Hepatosteatosis is usually accommodated by features of the metabolic syndrome(***,disturbances in triglyceride and glucose metabolism),and signs of hepatocellular damage,all of which are reflected by biomarkers,which poorly predict NAFLD as single item,but provide a cheap diagnostic alternative when integrated into composite liver fat *** liver index,NAFLD LFS,and hepatic steatosis index are common and accurate indices for NAFLD prediction,but show limited accuracy for liver fat *** indices are rarely *** fibrosis scores are commonly used in clinical practice,but their mandatory reflection of fibrotic reorganization,hepatic injury or systemic sequelae reduces sensitivity for the diagnosis of simple ***-induced liver fat changes are poorly reflected by liver fat indices,depending on the intervention and its specific impact of weight loss on *** limited validity in longitudinal settings stimulates research for new ***,hepatokines,markers of cellular integrity,genetic variants but also simple and inexpensive routine parameters might be potential ***,liver fat indices lack precision for NAFLD prediction or monitoring in individual patients,but in large cohorts they may substitute nonexistent imaging data and serve as a compound biomarker of metabolic syndrome and its cardiometabolic sequelae.

关键词： NAFLD liver fat indices fatty liver index Prediction Dietary intervention

Ursodeoxycholic acid as a means of preventing atherosclerosis,steatosis and liver fibrosis in patients with nonalcoholic fatty liver disease

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World Journal of Gastroenterology 2021年第10期27卷 959-975页

作者： Maria Nadinskaia Marina Maevskaya Vladimir Ivashkin Khava Kodzoeva Irina Pirogova Evgeny Chesnokov Alexander Nersesov Jamilya Kaibullayeva Akzhan Konysbekova Aigul Raissova Feruza Khamrabaeva Elena Zueva Department of Propaedeutics of Internal Diseases Gastroenterology and HepatologySechenov First Moscow State Medical University(Sechenov University)Moscow 119991Russia Vasilenko Clinic of Internal Diseases Propedeutics Gastroenterology and HepatologyUniversity Clinical Hospital№2Sechenov First Moscow State Medical University(Sechenov University)Moscow 119991Russia LLC MC“Lotus” Center for Gastroenterology and HepatologyChelyabinsk 454092Russia Department of Hospital Therapy with the Course of Endocrinology and Clinical Pharmacology Tyumen State Medical UniversityTyumen 625003Russia Department of Gastroenterology S.Asfendiyarov Kazakh National Medical UniversityAlmaty 050000Kazakhstan Functional and Ultrasound Diagnostics Scientific and Research Institute of Cardiology and Internal DiseasesAlmaty 050000Kazakhstan Department of Internal Diseases Scientific and Research Institute of Cardiology and Internal DiseasesAlmaty 050000Kazakhstan Faculty of Therapy Tashkent Institute of Advanced Medical StudiesTashkent 100007Uzbekistan Department of Therapy№1 with Training General Practitioners Tashkent Medical AcademyTashkent 100109Uzbekistan

BACKGROUND Atherosclerotic cardiovascular disease(ASCVD)is the leading cause of mortality in patients with nonalcoholic fatty liver disease(NAFLD).Weight loss is a key factor for successful NAFLD and CVD *** acid(UDCA),which is one of the first-line therapeutic agents for treatment of NAFLD,is reported to have a beneficial effect on dyslipidemia and ASCVD risk because of antioxidant *** To evaluate the effects of 6 mo of UDCA treatment on hepatic function tests,lipid profile,hepatic steatosis and fibrosis,atherogenesis,and ASCVD risk in men and women with NAFLD,as well as to assess the impact of>5%weight reduction on these *** An open-label,multicenter,international noncomparative trial was carried out at primary health care settings and included 174 patients with ultrasound-diagnosed NAFLD who received 15 mg/kg/d UDCA for 6 mo and were prescribed lifestyle modification with diet and *** efficacy criteria were liver enzymes,lipid profile,fatty liver index(FLI),noninvasive liver fibrosis tests(nonalcoholic fatty liver disease fibrosis score and liver fibrosis index),carotid intima-media thickness(CIMT),and ASCVD risk *** test statistical hypotheses,the Wilcoxon test,paired t-test,Fisher’s exact test,and Pearson's chi-squared test were *** The alanine aminotransferase(ALT)level changed by-14.1 U/L(-31.0;-5.3)from baseline to 3 mo and by-6.5 U/L(-14.0;0.1)from 3 to 6 *** magnitude of ALT,aspartate transaminase,and glutamyltransferase decrease was greater during the first 3 mo of treatment compared to the subsequent 3 mo(Pfatty liver disease

关键词： Ursodeoxycholic acid Nonalcoholic fatty liver disease liver function tests fatty liver index Carotid intima-media thickness Atherosclerotic cardiovascular disease

A novel model for predicting fatty liver disease by means of an artificial neural network

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Gastroenterology Report 2021年第1期9卷 31-37,I0001,I0002页

作者： Yi-Shu Chen Dan Chen Chao Shen Ming Chen Chao-Hui Jin Cheng-Fu Xu Chao-Hui Yu You-Ming Li Department of Gastroenterology The First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouZhejiangP.R.China Health Management Center The First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouZhejiangP.R.China Hithink Royal Flush Information Network Co. LtdHangzhouZhejiangP.R.China

Background:The artificial neural network(ANN)emerged recently as a potent diagnostic tool,especially for complicated systemic *** study aimed to establish a diagnostic model for the recognition of fatty liver disease(FLD)by virtue of the ***:A total of 7,396 pairs of gender-and age-matched subjects who underwent health check-ups at the First Affiliated Hospital,College of Medicine,Zhejiang University(Hangzhou,China)were enrolled to establish the ANN *** available in health check-up reports were utilized as potential input *** performance of our model was evaluated through a receiver-operating characteristic(ROC)curve *** outcome measures included diagnostic accuracy,sensitivity,specificity,Cohen’s k coefficient,Brier score,and Hosmer-Lemeshow *** fatty liver index(FLI)and the Hepatic Steatosis index(HSI),retrained using our training-group data with its original designated input variables,were used as comparisons in the capability of FLD ***:Eight variables(age,gender,body mass index,alanine aminotransferase,aspartate aminotransferase,uric acid,total triglyceride,and fasting plasma glucose)were eventually adopted as input nodes of the ANN *** applying a cut-off point of 0.51,the area under ROC curves of our ANN model in predicting FLD in the testing group was 0.908[95%confidence interval(CI),0.901-0.915]—significantly higher(P<0.05)than that of the FLI model(0.881,95%CI,0.872-0.891)and that of the HSI model(0.885;95%CI,0.877-0.893).Our ANN model exhibited higher diagnostic accuracy,better concordance with ultrasonography results,and superior capability of calibration than the FLI model and the HSI ***:Our ANN system showed good capability in the diagnosis of *** is anticipated that our ANN model will be of both clinical and epidemiological use in the future.

关键词： artificial neural network diagnostic model fatty liver disease fatty liver index Hepatic Steatosis index uric acid

Discrepancies between Nonalcoholic and Metabolic-associated fatty liver Disease by Multiple Steatosis Assessment

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Journal of Clinical and Translational Hepatology 2022年第6期10卷 1013-1026页

作者： Congxiang Shao Junzhao Ye Xin Li Yansong Lin Shiting Feng Bing Liao Wei Wang Xiaorong Gong Bihui Zhong Department of Gastroenterology of the First Affiliated Hospital Sun Yat-sen UniversityGuangzhouGuangdongChina Department of Gastroenterology Affiliated Dongguan People’s HospitalSouthern Medical University(Dongguan People’s Hospital)DongguanGuangdongChina Department of Radiology of the First Affiliated Hospital Sun Yat-sen Univer-sityGuangzhouGuangdongChina Department of Pathology of the First Affiliated Hospital Sun Yat-sen UniversityGuangzhouGuangdongChina Department of Medical Ultrasonics of the First Affiliated Hospital Sun Yat-sen UniversityGuangzhouGuangdongChina Department of Gastroenterology First Affiliated HospitalGuangzhou Medical UniversityGuangzhouGuangdongChina

Background and Aims:The redefinition of metabolic-as-sociated fatty liver disease(MAFLD)from nonalcoholic fat-ty liver disease(NAFLD)has caused a revolution in clinical practice,and the characteristics of patients with steatosis but not MAFLD remain *** aims were to compare the diagnosis rate of MAFLD in NAFLD using different steato-sis methods and explore the features of non-MAFLD-NAFLD and ***:A cross-sectional study enrolling consecutive individuals was conducted at three medical centers in southern China from January 2015 to September *** was evaluated by liver biopsy or magnetic resonance imaging-based proton density fat frac-tion(MRI-PDFF),ultrasound,controlled attenuation param-eter(CAP),and fatty liver index(FLI).Fibrosis was assessed by the NAFLD fibrosis score,transient elastography,or shear wave ***:The study enrolled 14,985 Chi-nese *** agreement of MAFLD and NAFLD diagnoses were 83%for FLI,95%for ultrasound,94%for both CAP and MRI-PDFF,and 95%for liver *** body mass index,blood pressure and lipid levels among non-MAFLD-NAFLD pa-tients were similar metabolic parameters(p>0.05 for all),but not the alanine aminotransferase and the proportion of pa-tients with insulin resistance,which were significantly higher in non-MAFLD-NAFLD with significant ***:The new MAFLD definition ruled out 5-17%of NAFLD *** and MAFLD-NAFLD involved more severe metabolic abnormalities than MAFLD and ***-MAFLD-NAFLD patients with significant fibrosis had more se-vere liver injury and increased glycemic dysregulation within the normal *** should be paid to its progression.

关键词： Controlled attenuation parameter fatty liver index liver biopsy Metabolic-associated fatty liver disease Magnetic resonance imaging-based proton density fat fraction

Non-alcoholic fatty liver disease:a multidisciplinary clinical practice approach—the institutional adaptation to existing Clinical Practice Guidelines

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Emergency and Critical Care Medicine 2022年第1期2卷 12-22页

作者： Zoran Gluvic Ratko Tomasevic Ksenija Bojovic Milan Obradovic Esma R.Isenovic University Clinical-Hospital Centre Zemun-Belgrade Clinic of Internal MedicineSchool of MedicineUniversity of BelgradeBelgradeSerbia Clinical Centre of Serbia Clinic of Infectious and Tropical DiseasesSchool of MedicineUniversity of BelgradeBelgradeSerbia Department of Radiobiology and Molecular Genetics “VINČA”Institute of Nuclear Sciences-National Institute of thеRepublic of SerbiaUniversity of BelgradeBelgradeSerbia

Non-alcoholic fatty liver disease(NAFLD)is among the most frequently encountered chronic liver diseases in everyday clinical *** is considered the hepatic manifestation of metabolic ***,liver biopsy is still the gold standard for NAFLD confirmation and assessing NAFLD’s possible progression to non-alcoholic steatohepatitis,fibrosis,cirrhosis,and hepatocellular *** of the high prevalence of NAFLD and potential associated risks of invasive diagnostic procedures,it is of great interest to recruit the patients for liver ***,as the presence of liver fibrosis determines the further clinical course,liver biopsy is expectedly reserved for those with increased fibrosis *** quality of liver biopsy recruitment and patient monitoring could be significantly improved by using non-invasive tools to assess liver fibrosis presence and interactive collaboration between general practitioners,gastroenterologists,and *** a result,the quality of liver biopsy recruitment and patients monitoring could be significantly ***,we proposed clinical practice guidelines that could be implemented for everyday clinical practice in NAFLD patients.

关键词： Diagnostics of NAFLD fatty liver index Fibrosis score-4 Management of NAFLD Non-alcoholic fatty liver disease