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Recommendations and Clinical Guidance for Children with Metabolic-associated Liver Disease duringthe COVID-19 Pandemic0

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Journal of Clinical and Translational Hepatology 2021年第1期9卷 1-2页

作者： Yong-Hai Zhou rafael s.rios Kenneth I.Zheng Ming-Hua Zheng Department of Pediatrics The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhouZhejiangChina MAFLD Research Center Department of HepatologyThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiangChina Institute of Hepatology Wenzhou Medical UniversityWenzhouZhejiangChina Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province WenzhouZhejiangChina

The outbreak of coronavirus disease-2019(COVID-19),a new disease caused by the severe acute respiratory syndrome coronavirus 2(sARs-CoV-2)in December 2019 affected most countries in the world within just a few *** March 11,2020,the Director-General at the World Health Organization(WHO)declared that COVID-19 can be considered a pandemic,and as of January 11,2021,there were over 88.8 million cases of COVID-19 worldwide and 1.9 million deaths reported by *** order to prevent the further spread of this epidemic outbreak,measures such as social distancing,stay-at-home orders,and school closure were executed in many ***,these measures also greatly reduced the opportunities for physical activity among *** on past experience,there are indications that an increased rate of weight gain occurs during summer school vacation for overweight ***,it is reasonable to speculate that under the influence of the COVID-19 epidemic,long-term school closures may significantly increase the risk of weight gain in obese *** children with metabolic-associated fatty liver disease(MAFLD),formerly known as nonalcoholic fatty liver disease,weight reduction through lifestyle changes(caloric restriction and physical activity)is considered as the first step in reversing disease progression,which makes managing MAFLD in children quite difficult during the ongoing COVID-19 *** addition,several studies found a significant correlation between a higher risk of severe illness from COVID-19 and metabolic disorders(***,obesity,MAFLD).

关键词： COVID-19 MAFLD Children

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Non-alcoholic steatohepatitis and risk of hepatocellular carcinoma

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Chinese Medical Journal 2021年第24期134卷 2911-2921页

作者： rafael s.rios Kenneth I.Zheng Ming-Hua Zheng NAFLD Research Center Department of Hepatologythe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang 325000China

The emergence of non-alcoholic fatty liver disease(NAFLD)as the leading chronic liver disease worldwide raises some *** particular,NAFLD is closely tied to sedentary lifestyle habits and associated with other metabolic diseases,such as obesity and *** the end of the disease spectrum,non-alcoholic steatohepatitis(NAsH)may progress to cirrhosis and hepatocellular carcinoma(HCC),representing a serious health problem to modern ***,an increasing number of HCC cases originating from this progressive disease spectrum have been identified,with different levels of severity and *** the current guidelines by placing a bigger focus on this emerging cause and highlighting some of its unique features is ***,the drivers of the disease are complex and multifactorial,in order to improve future outcomes,having a better understanding of NAsH progression into HCC may be *** risks that can promote disease progression and currently available management strategies employed to monitor and treat NAsH-related HCC make up the bulk of this review.

关键词： Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis Liver disease Hepatocellular carcinoma Insulin resistance Oxidative stress Metabolic associated fatty liver disease

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COVID-19 and Liver Dysfunction:Current Insights and Emergent Therapeutic strategies

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Journal of Clinical and Translational Hepatology 2020年第1期8卷 18-24页

作者： Gong Feng Kenneth I.Zheng Qin-Qin Yan rafael s.rios Giovanni Targher Christopher D.Byrne sven Van Poucke Wen-Yue Liu Ming-Hua Zheng Xi’an Medical University Xi’anChina NAFLD Research Center Department of Hepatologythe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina section of Endocrinology Diabetes and MetabolismDepartment of MedicineUniversity and Azienda Ospedaliera Universitaria Integrata of VeronaVeronaItaly southampton National Institute for Health Research Biomedical Research Center University Hospital SouthamptonSouthampton General HospitalSouthamptonUK Ziekenhuis Oost-Limburg Department of AnesthesiologyCritical CareEmergency Medicine and Pain TherapyGenkBelgium Department of Endocrinology the First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina Institute of Hepatology Wenzhou Medical UniversityWenzhouChina Key Laboratory of Diagnosis and Treatment for The Development of Chronic Liver Disease in Zhejiang Province WenzhouChina

The outbreak of coronavirus disease 2019(COVID-19),caused by the severe acute respiratory syndrome coronavirus 2(sARs-CoV-2),has attracted increasing worldwide *** of liver damage or dysfunction(mainly characterized by moderately elevated serum aspartate aminotransferase lev-els)have been reported among patients with ***,it is currently uncertain whether the COVID-19-related liver damage/dysfunction is due mainly to the viral infection per se or other coexisting conditions,such as the use of potentially hepatotoxic drugs and the coexistence of sys-temic inflammatory response,respiratory distress syndrome-induced hypoxia,and multiple organ *** on the current evidence from case reports and case series,this review article focuses on the demographic and clinical characteristics,potential mechanisms,and treatment options for COVID-19-related liver *** review also describes the geo-graphical and demographic distribution of COVID-19-related liver dysfunction,as well as possible underlying mechanisms linking COVID-19 to liver dysfunction,in order to facilitate future drug development,prevention,and control measures for COVID-19.

关键词： COVID-19 Liver dysfunction sARs-CoV-2

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Non-invasive fibrosis assessment in non-alcoholic fatty liver disease

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Chinese Medical Journal 2020年第22期133卷 2743-2745页

作者： rafael s.rios Kenneth I Zheng Giovanni Targher Christopher D.Byrne Ming-Hua Zheng Department of Hepatology MAFLD Research CenterThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang 325000China section of Endocrinology Diabetes and MetabolismDepartment of MedicineUniversity and Azienda Ospedaliera Universitaria Integrata of VeronaVerona 37126Italy southampton National Institute for Health Research Biomedical Research Center University Hospital SouthamptonSouthampton General HospitalSouthampton SO166YDUK Institute of Hepatology Wenzhou Medical UniversityWenzhouZhejiang 325000China Key Laboratory of Diagnosis and Treatment for The Development of Chronic Liver Disease in Zhejiang Province WenzhouZhejiang 325000China

Non-alcoholic fatty liver disease(NAFLD)is estimated to affect approximately 25%of the adult population worldwide.[1]NAFLD encompasses a histopathological spectrum of progressive pathologic conditions ranging from non... 详细信息

关键词： NAFLD liver pathologic

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Associations of Hydroxysteroid 17-beta Dehydrogenase 13 Variants with Liver Histology in Chinese Patients with Metabolicassociated Fatty Liver Disease

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Journal of Clinical and Translational Hepatology 2021年第2期9卷 194-202页

作者： Wen-Yue Liu Mohammed Eslam Kenneth I.Zheng Hong-Lei Ma rafael s.rios Min-Zhi Lv Gang Li Liang-Jie Tang Pei-Wu Zhu Xiao-Dong Wang Christopher D.Byrne Giovanni Targher Jacob George Ming-Hua Zheng Department of Endocrinology The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiangChina storr Liver Centre Westmead Institute for Medical ResearchWestmead Hospital and University of SydneyWestmeadSydneyAustralia NAFLD Research Center Department of HepatologyThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiangChina Department of Biostatistics Zhongshan HospitalFudan UniversityShanghaiChina Department of Laboratory Medicine The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiangChina Institute of Hepatology Wenzhou Medical UniversityWenzhouZhejiangChina southampton National Institute for Health Research Biomedical Research Centre University Hospital SouthamptonSouthampton General HospitalSouthamptonUK section of Endocrinology Diabetes and MetabolismDepartment of MedicineUniversity and Azienda Ospedaliera Universitaria Integrata of VeronaVeronaItaly Key Laboratory of Diagnosis and Treatment for The Development of Chronic Liver Disease in Zhejiang Province WenzhouZhejiangChina

Background and Aims:In Europeans,variants in the hydroxysteroid 17-beta dehydrogenase 13(HsD17B13)gene impact liver histology in metabolic-associated fatty liver disease(MAFLD).The impact of these variants in ethnic Chinese is *** aim of this study was to investigate the potential associations in Chinese ***:In total,427 Han Chinese with biopsy-confirmed MAFLD were *** single nucleotide polymorphisms in HsD17B13 were genotyped:rs72613567 and *** regression was used to test the association between the single nucleotide polymorphisms and liver ***:In our cohort,the minor allele TA of the rs72613567 variant was related to an increased risk of fibrosis[odds ratio(OR):2.93(1.20–7.17),p=0.019 for the additive model;OR:3.32(1.39–7.91),p=0.007 for the recessive model],representing an inverse association as compared to the results from European *** contrast,we observed a protective effect on fibrosis for the minor A allele carriers of the HsD17B13 rs6531975 variant[OR:0.48(0.24–0.98),p=0.043 for the additive model;OR:0.62(0.40–0.94),p=0.025 for the dominant model].HsD17B13 variants were only associated with fibrosis but no other histological ***,HsD17B13 rs6531975 modulated the effect of PNPLA3 rs738409 on hepatic ***:HsD17B13 rs72613567 is a risk variant for fibrosis in a Han Chinese MAFLD population but with a different direction for allelic association to that seen in *** data exemplify the need for studying diverse populations in genetic studies in order to fine map genome-wide association studies signals.

关键词： Metabolic-associated fatty liver disease(MAFLD) Nonalcoholic fatty liver disease(NAFLD) Hydroxysteroid 17-beta dehydrogenase 13(HsD17B13) single nucleotide polymorphism(sNP)

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A novel radiomics signature based on T2-weighted imaging accurately predicts hepatic inflammation in individuals with biopsy-proven nonalcoholic fatty liver disease:a derivation and independent validation study

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Hepatobiliary surgery and Nutrition 2022年第2期11卷 212-226,I0008-I0010页

作者： Zhong-Wei Chen Huan-Ming Xiao Xinjian Ye Kun Liu rafael s.rios Kenneth I.Zheng Yi Jin Giovanni Targher Christopher D.Byrne Junping shi Zhihan Yan Xiao-Ling Chi Ming-Hua Zheng Department of Radiology the First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina Department of Hepatology Guangdong Provincial Hospital of Chinese Medicinethe Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhouChina Department of Radiology the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhouChina NAFLD Research Center Department of Hepatologythe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina Department of Pathology the First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina section of Endocrinology Diabetes and MetabolismDepartment of MedicineUniversity and Azienda Ospedaliera Universitaria Integrata of VeronaVeronaItaly southampton National Institute for Health Research Biomedical Research Centre University Hospital SouthamptonSouthampton General HospitalSouthamptonUK Department of Hepatology The Affiliated Hospital of Hangzhou Normal UniversityHangzhouChina Institute of Hepatology Wenzhou Medical UniversityWenzhouChina Key Laboratory of Diagnosis and Treatment for The Development of Chronic Liver Disease in Zhejiang Province WenzhouChina

Background:Currently,there are no effective methods for assessing hepatic inflammation without resorting to histological examination of liver tissue obtained by biopsy.T2-weighted images(T2WI)are routinely obtained from liver magnetic resonance imaging(MRI)scan *** aimed to establish a radiomics signature based on T2WI(T2-Rs)for assessment of hepatic inflammation in people with nonalcoholic fatty liver disease(NAFLD).Methods:A total of 203 individuals with biopsy-confirmed NAFLD from two independent Chinese cohorts with liver MRI examination were enrolled in this *** hepatic inflammatory activity score(IAs)was calculated by the unweighted sum of the histologic scores for lobular inflammation and *** thousand and thirty-two radiomics features were extracted from the localized region of interest(ROI)in the right liver lobe of T2WI and,subsequently,selected by minimum redundancy maximum relevance and least absolute shrinkage and selection operator(LAssO)*** T2-Rs was calculated by adding the selected features weighted by their ***:Eighteen radiomics features from Laplacian of Gaussian,wavelet,and original images were selected for establishing *** T2-Rs value differed significantly between groups with increasing grades of hepatic inflammation(Ps yielded an area under the receiver operating characteristic(ROC)curve(AUROC)of 0.80[95%confidence interval(CI):0.71-0.89]for predicting hepatic inflammation in the training cohort with excellent *** AUROCs of T2-Rs in the internal cohort and external validation cohorts were 0.77(0.61-0.93)and 0.75(0.63-0.84),***:The T2-Rs derived from radiomics analysis of T2WI shows promising utility for predicting hepatic inflammation in individuals with NAFLD.

关键词： Nonalcoholic fatty liver disease(NAFLD) inflammation activity radiomics magnetic resonance imaging(MRI)

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Glycemic control predicts the risk of hepatic fibrosis in biopsy-proven NAFLD:a possible mediating role for leukemia inhibitory factor?

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iLIVER 2022年第1期1卷 30-34页

作者： Feng Gong Kenneth I.Zheng Liang-Jie Tang Gang Li rafael s.rios Ou-Yang Huang Yang-Yang Li Christopher D.Byrne Giovanni Targher Man Mi Na He Hong-Lei Ma Ming-Hua Zheng Xi'an Medical University China NAFLD Research Center Department of HepatologyThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina Department of Pathology The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina southampton National Institute for Health Research Biomedical Research Centre University Hospital SouthamptonSouthampton General HospitalSouthamptonUK section of Endocrinology Diabetes and MetabolismDepartment of MedicineUniversity and Azienda Ospedaliera Universitaria Integrata of VeronaVeronaItaly The First Affiliated Hospital of Xi'an Medical University Xi'anChina Institute of Hepatology Wenzhou Medical UniversityWenzhouChina Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province WenzhouChina

Background:Despite the clear link between nonalcoholic fatty liver disease(NAFLD)and type 2 diabetes mellitus,little is understood about how glycemic control impacts histological *** aimed to investigate the deeper association between hemoglobin A1c(HbA1c)and the histologic severity of liver ***:A total of 568 adults with biopsy-proven NAFLD from the PERsONs cohort in Wenzhou were *** association between mean HbA1c and hepatic histological features was investigated with ordinal logistic *** additive models were used to identify the non-linear relationship between HbA1c and increased fibrosis stage(stage F3).Causal mediation analysis was performed to calculate the indirect effect of the relationship between HbA1c and hepatic fibrosis mediated by ***:Every 1%increase in mean HbA1c was associated with 16%higher odds of increased fibrosis stage(odds ratio 1.16,95%CI 1.04–1.30),even after adjustment for confounding *** was a non-linear association between HbA1c and increased fibrosis stage(stage F3),and the HbA1c inflection point was 9.2%.In particular,the ORs on the left and right sides of this inflection point were 2.1(95%CI 1.4–3.3)and 0.1(95%CI 0–4.8),respectively.7%of the association(OR 1.07,95%CI 1.01–1.12)between HbA1c and liver fibrosis was mediated by leukemia inhibitory ***:Glycemic control predicts severity of hepatic fibrosis and leukemia inhibitory factor plays an intermediary role between them,and thus optimizing glycemic control may be a means of modifying the risk of fibrosis progression in NAFLD.

关键词： NAFLD Leukemia inhibitory factor Hepatic fibrosis

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LEARN algorithm:a novel option for predicting non-alcoholic steatohepatitis

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Hepatobiliary surgery and Nutrition 2023年第4期12卷 507-522,I0017-I0022页

作者： Gang Li Tian-Lei Zheng Xiao-Ling Chi Yong-Fen Zhu Jin-Jun Chen Liang Xu Jun-Ping shi Xiao-Dong Wang Wei-Guo Zhao Christopher D.Byrne Giovanni Targher rafael s.rios Ou-Yang Huang Liang-Jie Tang shi-Jin Zhang shi Geng Huan-Ming Xiao sui-Dan Chen Rui Zhang Ming-Hua Zheng MAFLD Research Center Department of Hepatologythe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina Artificial Intelligence Unit Department of Medical EquipmentThe Affiliated Hospital of Xuzhou Medical UniversityXuzhouChina Department of Hepatology Guangdong Provincial Hospital of Chinese Medicinethe Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhouChina Department of Hepatology and Infection Sir Run Run Shaw HospitalAffiliated with School of MedicineZhejiang UniversityHangzhouChina Hepatology Unit Department of Infectious DiseasesNanfang HospitalSouthern Medical UniversityGuangzhouChina Hepatology Unit Zengcheng BranchNanfang HospitalSouthern Medical UniversityGuangzhouChina Department of Hepatology Tianjin Second People’s HospitalTianjinChina Department of Liver Diseases Hangzhou Normal University Affiliated HospitalHangzhouChina Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province WenzhouChina southampton National Institute for Health and Care Research Biomedical Research Centre University Hospital Southampton&University of SouthamptonSouthampton General HospitalSouthamptonUK section of Endocrinology Diabetes and MetabolismDepartment of MedicineUniversity of VeronaVeronaItaly Department of Pathology the First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina Department of Nutrition the First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina Institute of Hepatology Wenzhou Medical UniversityWenzhouChina

Background:There is an unmet need for accurate non-invasive methods to diagnose non-alcoholic steatohepatitis(NAsH).since impedance-based measurements of body composition are simple,repeatable and have a strong association with non-alcoholic fatty liver disease(NAFLD)severity,we aimed to develop a novel and fully automatic machine learning algorithm,consisting of a deep neural network based on impedance-based measurements of body composition to identify NAsH[the bioeLectrical impEdance Analysis foR Nash(LEARN)algorithm].Methods:A total of 1,259 consecutive subjects with suspected NAFLD were screened from six medical centers across China,of which 766 patients with biopsy-proven NAFLD were included in final *** patients were randomly subdivided into the training and validation groups,in a ratio of 4:*** LEARN algorithm was developed in the training group to identify NAsH,and subsequently,tested in the validation ***:The LEARN algorithm utilizing impedance-based measurements of body composition along with age,sex,pre-existing hypertension and diabetes,was able to predict the likelihood of having *** algorithm showed good discriminatory ability for identifying NAsH in both the training and validation groups[area under the receiver operating characteristics(AUROC):0.81,95%CI:0.77-0.84 and AUROC:0.80,95%CI:0.73-0.87,respectively].This algorithm also performed better than serum cytokeratin-18 neoepitope M30(CK-18 M30)level or other non-invasive NAsH scores(including HAIR,ION,NICE)for identifying NAsH(P valuesH in different patient subgroups,as well as in subjects with partial missing body composition ***:The LEARN algorithm,utilizing simple easily obtained measures,provides a fully automated,simple,non-invasive method for identifying NAsH.

关键词： Non-alcoholic fatty liver disease(NAFLD) non-alcoholic steatohepatitis(NAsH) bioeLectrical impEdance Analysis foR Nash(LEARN)algorithm body composition

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PNPLA3 rs738409 C>G Variant Influences the Association Between Visceral Fat and significant Fibrosis in Biopsyproven Nonalcoholic Fatty Liver Disease

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Journal of Clinical and Translational Hepatology 2022年第3期10卷 439-448页

作者： Gang Li Liang-Jie Tang Pei-Wu Zhu Ou-Yang Huang rafael srios Kenneth IZheng sui-Dan Chen Hong-Lei Ma Giovanni Targher Christopher DByrne Xiao-Yan Pan Ming-Hua Zheng NAFLD Research Center Department of Hepatologythe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiangChina Department of Laboratory Medicine the First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiangChina Department of Pathology the First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiangChina section of Endocrinology Diabetes and MetabolismDepartment of MedicineUniversity and Azienda Ospedaliera Universitaria Integrata of VeronaVeronaItaly southampton National Institute for Health Research Biomedical Research Centre University Hospital SouthamptonSouthampton General HospitalSouthamptonUK Department of Endocrinology the First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiangChina Institute of Hepatology Wenzhou Medical UniversityWenzhouZhejiangChina Key Laboratory of Diagnosis and Treatment for The Development of Chronic Liver Disease in Zhejiang Province WenzhouZhejiangChina

Background and Aims:Intra-abdominal visceral fat accumulation and patatin-like phospholipase domain containing 3(PNPLA3)rs738409 G/C gene polymorphism confer a greater susceptibility to nonalcoholic fatty liver disease(NAFLD).We examined whether the relationship between visceral fat accumulation and liver disease severity may be influenced by PNPLA3 rs738409 ***:The variant of PNPLA3 rs738409 was genotyped within 523 Han individuals with biopsy-confirmed *** fat area(VFA)was measured by bioelectrical *** liver fibrosis(sF),defined as stage F≥2 on histology,was the outcome measure of ***:The distribution of PNPLA3 genotypes was CC:27.5%,CG:48.2%,and GG:24.3%.Higher VFA was associated with greater risk of having sF(adjusted-odds ratio[OR]:1.03;95%confidence interval[CI]:1.02–1.04,psubjects with the same VFA level,the risk of sF was greater among carriers of the rs738409 G genotype than among those who did *** analysis showed that PNPLA3 rs738409 significantly influenced the association between VFA and *** remained significantly associated with sF only among the rs738409 G-allele carriers(adjusted-OR:1.05;95%CI:1.03–1.08 for the GG group;and adjusted-OR:1.03;95%CI:1.01–1.04 for the GC group).There was a significant interaction between VFA and PNPLA3 rs738409 genotype(Pinteraction=0.004).Conclusions:PNPLA3 rs738409 G allele has a moderate effect on the association between VFA and risk of sF in adult individuals with biopsy-proven *** of the PNPLA3 rs738409 G allele and VFA interact to increase risk of sF。

关键词： Nonalcoholic fatty liver disease significant fibrosis Visceral fat area single nucleotide polymorphism Metabolic dysfunction-associated fatty liver disease

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Interaction of sAMM50-rs738491,PARVB-rs5764455 and PNPLA3-rs738409 Increases susceptibility to Nonalcoholic steatohepatitis

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Journal of Clinical and Translational Hepatology 2022年第2期10卷 219-229页

作者： Ke Xu Kenneth IZheng Pei-Wu Zhu Wen-Yue Liu Hong-Lei Ma Gang Li Liang-Jie Tang rafael srios Giovanni Targher Christopher DByrne Xiao-Dong Wang Yong-Ping Chen Ming-Hua Zheng NAFLD Research Center Department of HepatologyFirst Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiangChina Department of Thoracic surgery Shanghai Chest HospitalShanghai Jiao Tong UniversityShanghaiChina Department of Laboratory Medicine First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiangChina Department of Endocrinology First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiangChina section of Endocrinology Diabetes and MetabolismDepartment of MedicineUniversity and Azienda Ospedaliera Universitaria Integrata of VeronaVeronaItaly southampton National Institute for Health Research Biomedical Research Centre University Hospital SouthamptonSouthampton General HospitalSouthamptonUK Institute of Hepatology Wenzhou Medical UniversityWenzhouZhejiangChina Key Laboratory of Diagnosis and Treatment for The Development of Chronic Liver Disease in Zhejiang Province WenzhouZhejiangChina

Background and Aims:Previous studies have reported that the single nucleotide polymorphisms(sNPs)of sAMM50-rs738491,PARVB-rs5764455 and PNPLA3-rs738409 are associated with nonalcoholic fatty liver disease(NAFLD).However,no studies have examined the effect of interactions between these three genotypes to affect liver disease *** assessed the effect of these three sNPs on nonalcoholic steatohepatitis(NAsH)and also examined the gene-gene interactions in a Chinese population with biopsy-confirmed ***:We enrolled 415 consecutive adult individuals with biopsy-proven *** logistic regres-sion analysis was undertaken to test associations between NAsH and sNPs in sAMM50-rs738491,PARVB-rs5764455 and ***-gene interactions were ana-lyzed by performing a generalized multifactor dimensionality reduction(GMDR)***:The mean±standard deviation age of these 415 patients was 41.3±12.5 years,and 75.9%were *** with sAMM50-rs738491 TT,PARVB-rs5764455 AA or PNPLA3-rs738409 GG genotypes had a higher risk of NAsH,even after adjustment for age,sex and body mass *** analysis showed that the combination of all three sNPs was the best model for predicting ***,the odds ratio of the haplotype T-A-G for predicting the risk of NAsH was nearly three times higher than that of the haplotype ***:NAFLD patients carrying the sAMM50-rs738491 TT,PARVB-rs5764455 AA or PNPLA3-rs738409 GG genotypes are at greater risk of *** three sNPs may synergistically interact to increase susceptibility to NAsH.

关键词： Gene polymorphisms Gene-gene interaction sAMM50 PARVB PNPLA3 NAsH

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