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When a new definition overhauls perceptions of MAFLD related cirrhosis care

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Hepatobiliary Surgery and Nutrition 2020年第6期9卷 801-804页

作者： kenneth i.zheng Mohammed Eslam Jacob George Ming-Hua zheng MAFLD Research Center Department of Hepatologythe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina Storr Liver Centre Westmead Institute for Medical ResearchWestmead Hospital and University of SydneySydneyAustralia institute of Hepatology Wenzhou Medical UniversityWenzhouChina Key Laboratory of Diagnosis and Treatment for The Development of Chronic Liver Disease in Zhejiang Province WenzhouChina

Metabolic-associated fatty liver disease(MAFLD)(1),formerly known as non-alcoholic fatty liver disease,is a major causes of liver cirrhosis(2).MAFLD represents a growing global health and economic burden since approximately one in four people have the disease(3).As a consequence,MAFLD-related cirrhosis is expected to become the leading cause for liver failure and liver cancer,and the major indication for liver transplantation this century(3).

关键词： cirrhosis MAF Metabolic

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

Metabolic Acidosis in Critically ill Cirrhotic Patients with Acute Kidney injury

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Journal of Clinical and Translational Hepatology 2019年第2期7卷 112-121页

作者： Dan-Qin Sun Lai Zhang Chen-Fei.zheng Wen-Yue Liu kenneth i.zheng Xiao-Ming Chen Ming-Hua zheng Wei-Jie Yuan Department of Nephrology The Affiliated Wuxi No.2 People’s Hospital of Nanjing Medical UniversityWuxiChina Department of Nephrology Shanghai General Hospital of Nanjing Medical UniversityShanghaiChina Department of Nephrology The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina Department of Endocrinology The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina NAFLD Research Center Department of Hepatologythe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina Zhejiang Engineering Research Center of intelligent Medicine The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina institute of Hepatology Wenzhou Medical UniversityWenzhouChina Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province WenzhouChina

Background and Aims:The metabolic acid-base disorders have a high incidence of acute kidney injury(AKi)in critically ill cirrhotic patients(CiCPs).The aims of our study were to ascertain the composition of metabolic acidosis of CiCPs with AKi and explore its relationship with hospital ***:Three-hundred and eighty consecutive CiCPs with AKi were eligible for the cohort ***,clinical and laboratory parameters were recorded and arterial acid-base state was analyzed by the Stewart and Gilfix ***:Net metabolic acidosis,lactic acidosis,acidosis owing to unmeasured anions,acidemia,and dilutional acidosis were less frequent in the non-survival group compared to the survival group of *** presence of acidemia,acidosis owing to unmeasured anions,and lactic acidosis were independently associated with increased risk of intensive care unit 30-day mortality,with hazard ratios of 2.11(95%confidence interval(Ci):1.43–3.12),3.38(95%Ci:2.36–4.84),and 2.16(95%Ci:1.47–3.35),*** full adjustment for confounders,the relationship between acidosis owing to unmeasured anions with hospital mortality was still significant,with hazard ratio of 2.29(95%Ci:1.22–4.30).Furthermore,arterial lactate concentration in combination with chronic liver failure-sequential organ failure assessment and BEUMA had the strongest ability to differentiate 30-day mortality(area under the receiver operating characteristic curve:0.79,95%Ci:0.74–0.83).

关键词： Metabolic acidosis Critically ill cirrhotic patients Acute kidney injury Hospital morality

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

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

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)

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(Pielded 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)

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

Hemophagocytosis in a Severe COViD-19 Patient

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infectious Diseases & immunity 2022年第1期2卷 55-57页

作者： kenneth i.zheng Xianghong Jin Xuanru Lin Hong Lu Wenyue Liu Minghua zheng MAFLD Research Center Department of Hepatologythe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang 325035China Department of Hematology Peking Union Medical College HospitalChinese Academy of Medical SciencesBeijing 100006China Department of Hematology the First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang 325035China Department of Laboratory Medicine the First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang 325035China Department of Endocrinology the First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang 325035China

The novel coronavirus(SARS-CoV-2)infection has become a heavy burden on global *** the coronavirus disease 2019(COViD-19)may adversely affect multiple organs and systems of infected patients,to the best of our knowledge,there is little investigation of the SARS-CoV-2’s impact on bone *** clinical and cytological findings in this case of severe COViD-19 infection provide novel insights into the pathogenesis of SARS-CoV-2 infection in the hematopoietic *** recommend that physicians consider SARS-CoV-2 infection’s effect on bone marrow in patients who are slow to recover and suggest that a better understanding of the bone marrow morphology in COViD-19-infected patients is needed.

关键词： Bone marrow COViD-19 Hemophagocytosis