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Nonalcoholic Fatty Liver Disease and the Intestinal Microbiome:An Inseparable Link

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Journal of Clinical and Translational Hepatology 2023年第7期11卷 1498-1507页

作者： Maria Effenberger Christoph Grander Felix Grabherr herbert tilg Department of Internal Medicine I GastroenterologyHepatologyEndocrinology and MetabolismMedical University of InnsbruckInnsbruckAustria

Nonalcoholic fatty liver disease(NAFLD)particularly affects patients with type 2 diabetes and *** incidence of NAFLD has increased significantly over the last decades and is now pandemically across the *** is a complex systemic disease comprising hepatic lipid accumulation,inflammation,lipotoxicity,gut dysbiosis,and insulin resistance as main features and with the potential to progress to cirrhosis and hepatocellular carcinoma(HCC).In numerous animal and human studies the gut microbiota plays a key role in the pathogenesis of NAFLD,NAFLD-cirrhosis and NAFLD-associated *** is the driver of inflammation,insulin resistance,and liver ***,western diet,obesity,and metabolic disorders may alter the gut microbiota,which activates innate and adaptive immune responses and fuels hereby hepatic and systemic *** carbohydrates are fermented by the gut microbiota to produce important metabolites,such as short-chain fatty acids and *** animal and human studies suggested a pivotal role of these metabolites in the progression of NAFLD and its ***,modification of the gut microbiota and/or the metabolites could even be beneficial in patients with NAFLD,NAFLD-cirrhosis,and NAFLD-associated *** this review we collect the evidence that exogenous and endogenous hits drive liver injury in NAFLD and propel liver fibrosis and the progressing to advanced disease *** can be seen as the product of a complex interplay between gut microbiota,the immune response and ***,the challenge will be to understand its pathogenesis and to develop new therapeutic strategies.

关键词： Nonalcoholic fatty liver disease NAFLD Microbiome Metabolome

Gut microbiome,liver immunology,and liver diseases

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Cellular & Molecular Immunology 2021年第1期18卷 4-17页

作者： Rui Wang Ruqi Tang Bo Li Xiong Ma Bernd Schnabl herbert tilg Division of Gastroenterology and Hepatology Key Laboratory of Gastroenterology and HepatologyMinistry of HealthState Key Laboratory for Oncogenes and Related GenesRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai Institute of Digestive Disease145 Middle Shandong Road200001 ShanghaiChina Department of Medicine University of CaliforniaSan DiegoLa JollaCAUSA Department of Medicine VA San Diego Healthcare SystemSan DiegoCAUSA Department of Internal Medicine I GastroenterologyHepatologyEndocrinology&MetabolismMedical University InnsbruckInnsbruckAustria

The gut microbiota is a complex and plastic consortium of microorganisms that are intricately connected with human *** liver is a central immunological organ that is particularly enriched in innate immune cells and constantly exposed to circulating nutrients and endotoxins derived from the gut *** delicate interaction between the gut and liver prevents accidental immune activation against otherwise harmless *** on the interplay between the gut microbiota and liver has assisted in understanding the pathophysiology of various liver *** immense importance is the step from high-throughput sequencing(correlation)to mechanistic studies(causality)and therapeutic ***,we review the gut microbiota,liver immunology,and the interaction between the gut and *** addition,the impairment in the gut-liver axis found in various liver diseases is reviewed here,with an emphasis on alcohol-associated liver disease(ALD),nonalcoholic fatty liver disease(NAFLD),and autoimmune liver disease(AILD).On the basis of growing evidence from these preclinical studies,we propose that the gut-liver axis paves the way for targeted therapeutic modalities for liver diseases.

关键词： Gut-liver axis Alcohol liver disease Nonalcoholic fatty liver disease Autoimmune liver disease Microbiome

Multiple cerebral lesions in a patient with refractory celiac disease:A case report

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World Journal of Gastroenterology 2020年第47期26卷 7584-7592页

作者： Lena Horvath Georg Oberhuber Andreas Chott Maria Effenberger herbert tilg Eberhard Gunsilius Dominik Wolf Sarah Iglseder Department of Internal Medicine V(Hematology and Medical Oncology) Medical University InnsbruckInnsbruck 6020Austria InnPath GmbH Institute of PathologyInnsbruck 6020Austria Ottakring Clinic Institute of Pathology and MicrobiologyVienna 1160Austria Department of Internal Medicine I(Gastroenterology HepatologyEndocrinology and Metabolism)Medical University InnsbruckInnsbruck 6020Austria Department of Neurology Medical University InnsbruckInnsbruck 6020Austria

BACKGROUND Enteropathy-associated T cell lymphoma(EATL)is an aggressive intestinal T cell lymphoma derived from intraepithelial lymphocytes,which occurs in individuals with celiac disease(CD).Cerebral involvement is an extremely rare condition and as described so far,lymphoma lesions may present as parenchymal predominantly supratentorial or leptomeningeal *** describe a case of EATL with multifocal supra-and infratentorial brain involvement in a patient with refractory celiac disease(RCD).CASE SUMMARY A 58-years old man with known CD developed ulcerative jejunitis and was diagnosed with RCD type *** months later he presented with subacute cerebellar symptoms(gait ataxia,double vision,dizziness).Cranial magnetic resonance imaging(MRI)revealed multifocal T2 hyperintense supra-and infratentorial *** studies of blood and cerebrospinal fluid were inconspicuous for infectious,inflammatory or autoimmune diseases.18Ffluorodeoxyglucose-positron emission tomography/computed tomography(18FDG-PET/CT)scan showed a suspect hypermetabolic lesion in the left upper abdomen and consequent surgical jejunal resection revealed the diagnosis of *** the diagnostic work-up,neurological symptoms aggravated and evolved refractory to high-dosage *** MRI scans showed progressive cerebral lesions,highly suspicious for lymphoma and methotrexate chemotherapy was ***,clinically the patient responded only ***,cerebral biopsy confirmed the diagnosis of cerebral involvement of *** the poor prognosis and deterioration of the performance status,best supportive care was *** patient passed away three weeks after *** EATL with cerebral involvement must be considered as a possible differential diagnosis in patients with known RCD presenting with neurological symptoms.

关键词： Enteropathy-associated T cell lymphoma Brain neoplasm Celiac disease Cerebellar syndrome Case report

18F-DOPA PET/CT可更准确识别肾上腺外副神经节瘤的侵犯范围:与123I-MIBG SPECT/CT显像比较

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中华核医学与分子影像杂志 2018年第1期38卷 71-71页

作者：唐军 Alexander Stephan Kroiss Christian Uprimny Barry Lynn Shulkn Andreas Freeh herbert tilg Rudolf Wolfgang Gasser Georg Mathias Sprinzl Leonhard Gruber Claudius Thorné Clemens Plangger Christoph Url Gustav Fraedrich Irene Johanna Virgolini 上海交通大学医学院附属苏州九龙医院核医学科 Department of Nuclear Medicine Medical University Innsbruck

目的通过功能显像、解剖影像及两者融合,比较123I-间碘苄胍(MIBG)SPECT/CT显像和18F-多巴(DOPA)PET/CT显像对肾上腺外副神经节瘤(PGL)患者分期的准确性。方法共纳入有解剖学和(或)组织学证实的3例男性和7例女性患者(年龄26～73岁),其中... 详细信息

目的通过功能显像、解剖影像及两者融合,比较123I-间碘苄胍(MIBG)SPECT/CT显像和18F-多巴(DOPA)PET/CT显像对肾上腺外副神经节瘤(PGL)患者分期的准确性。方法共纳入有解剖学和(或)组织学证实的3例男性和7例女性患者(年龄26～73岁),其中3例有转移性头颈部PGL(HNPGL)或多灶性PGL,余7例未发现转移瘤。在CT解剖影像、18F-DOPA和123I-MIBG的功能显像、123I-MIBG SPECT/CT间进行分析比较。对每例患者和每个病灶进行分析。结果分析每例患者发现,对于非转移性和转移性多灶性PGL,18F-DOPA PET的探测率为100%,单独123I-MIBCG平面显像的探测率为10.0%,123I-MIBG SPECT/CT为20.0%。分析每个病灶的结果显示,与单独CT相比,18F-DOPA PET的灵敏度为69.2%(P<0.001),而单独123I-MIBG平面显像的灵敏度为5.6%,123IMIBG SPECT/CT为11.1%(P<0.000 1)。总体而言,18F-DOPA PET发现了18个病灶,单独CT发现了26个病灶,而单独123I-MIBG平面显像仅找到1个病灶,123I-MIBG SPECT/CT找到2个病灶。结论在HNPGL分期中,18F-DOPA PET比123I-MIBG平面显像和SPECT/CT的灵敏度更高。功能性和解剖性影像的结合(PET/CT)可排除肾上腺外PGL患者的转移性病灶。

关键词： 123I-MIBG 18F-DOPA PET/CT 肾上腺外副神经节瘤

An international Delphi consensus statement on metabolic dysfunction-associated fatty liver disease and risk of chronic kidney disease

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Hepatobiliary Surgery and Nutrition 2023年第3期12卷 386-403,I0014-I0016页

作者： Dan-Qin Sun Giovanni Targher Christopher D.Byrne David C.Wheeler Vincent Wai-Sun Wong Jian-Gao Fan herbert tilg Wei-Jie Yuan Christoph Wanner Xin Gao Michelle T.Long Mehmet Kanbay Mindie H.Nguyen Sankar D.Navaneethan Yusuf Yilmaz Yuli Huang Rino A.Gani Pierluigi Marzuillo Jérôme Boursier Huijie Zhang Chan-Young Jung Jin Chai Luca Valenti George Papatheodoridis Giovanni Musso Yu-Jun Wong Mohamed El-Kassas Nahum Méndez-Sánchez Silvia Sookoian Michael Pavlides Ajay Duseja Adriaan G.Holleboom Junping Shi Wah-Kheong Chan Yasser Fouad Junwei Yang Sombat Treeprasertsuk Helena Cortez-Pinto Masahide Hamaguchi Manuel Romero-Gomez Mamun Al Mahtab Ponsiano Ocama Atsushi Nakajima Chunsun Dai Mohammed Eslam Lai Wei Jacob George Ming-Hua Zheng Department of Nephrology Jiangnan University Medical CenterWuxiChina Affiliated Wuxi Clinical College of Nantong University WuxiChina Section of Endocrinology Diabetes and MetabolismDepartment of MedicineAzienda Ospedaliera Universitaria Integrata VeronaVeronaItaly Southampton National Institute for Health and Care Research Biomedical Research Centre University Hospital Southamptonand Southampton General HospitalUniversity of SouthamptonSouthamptonUK Department of Renal Medicine University College LondonLondonUK Department of Medicine and Therapeutics Chinese University of Hong KongHong KongChina Center for Fatty Liver Department of GastroenterologyXin Hua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina Department of Internal Medicine I GastroenterologyEndocrinology&MetabolismMedical University InnsbruckInnsbruckAustria Department of Nephrology Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Division of Nephrology Department of MedicineWürzburg University ClinicWürzburgGermany Department of Endocrinology and Metabolism Zhongshan HospitalFudan UniversityShanghaiChina Section of Gastroenterology Boston Medical CenterBoston University School of MedicineBostonMAUSA Division of Nephrology Department of Medicine(M.K.)Koc University School of MedicineIstanbulTurkey Division of Gastroenterology and Hepatology Department of MedicineStanford University Medical CenterPalo AltoCAUSA Department of Epidemiology and Population Health Stanford University Medical CenterPalo AltoCAUSA Section of Nephrology and Institute of Clinical and Translational Research Baylor College of Medicineand Michael E.DeBakey VA Medical CenterHoustonTXUSA Department of Gastroenterology School of MedicineMarmara UniversityIstanbulTurkey Department of Gastroenterology School of MedicineRecep Tayyip Erdoğan UniversityRizeTurkey Department of Cardiology Shunde HospitalSouthern Medical UniversityFoshanChina Division of Hepat

Background:With the rising global prevalence of fatty liver disease related to metabolic dysfunction,the association of this common liver condition with chronic kidney disease(CKD)has become increasingly *** 2020,the more inclusive term metabolic dysfunction-associated fatty liver disease(MAFLD)was proposed to replace the term non-alcoholic fatty liver disease(NAFLD).The observed association between MAFLD and CKD and our understanding that CKD can be a consequence of underlying metabolic dysfunction support the notion that individuals with MAFLD are at higher risk of having and developing CKD compared with those without ***,to date,there is no appropriate guidance on CKD in individuals with ***,there has been little attention paid to the link between MAFLD and CKD in the Nephrology *** and Results:Using a Delphi-based approach,a multidisciplinary panel of 50 international experts from 26 countries reached a consensus on some of the open research questions regarding the link between MAFLD and ***:This Delphi-based consensus statement provided guidance on the epidemiology,mechanisms,management and treatment of MAFLD and CKD,as well as the relationship between the severity of MAFLD and risk of CKD,which establish a framework for the early prevention and management of these two common and interconnected diseases.

关键词： Metabolic dysfunction-associated fatty liver disease(MAFLD) non-alcoholic fatty liver disease(NAFLD) chronic kidney disease(CKD) consensus

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优化固井作业的温度数据

钻井工艺情报 1991年第4期 24-33页

作者： tilg.,SE 王芳

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2016年欧洲粪菌移植共识介绍

胃肠病学和肝病学杂志 2017年第9期26卷 961-965页

作者：李超谈路轩张馨梅汪志兵张振玉 Cammarota G Ianiro G tilg H 南京医科大学附属南京医院(南京市第一医院)消化科江苏南京210000

粪菌移植(fecal microbiota transplantation,FMT)是治疗艰难梭菌感染的一个重要选择。研究表明,FMT也可能在管理与肠道微生物群变化相关的其他疾病方面发挥作用。虽然医疗界正在用最新的观点评估FMT,且患者正在变得越来越了解FMT,但在... 详细信息

粪菌移植(fecal microbiota transplantation,FMT)是治疗艰难梭菌感染的一个重要选择。研究表明,FMT也可能在管理与肠道微生物群变化相关的其他疾病方面发挥作用。虽然医疗界正在用最新的观点评估FMT,且患者正在变得越来越了解FMT,但在将非标准化的治疗方案转化为安全和管理恰当的临床实践中存在技术和后勤问题。鉴于此,需要一个基于证据的指南来推动FMT的实际实施。在这个欧洲共识会议上,来自10个国家的28名专家,分成多个小组并通过循证过程对以下事项提供了指南:FMT适应证、供体选择、粪便材料的准备、临床管理和移植实施,以及建立一个FMT中心的基本要求。每个小组提出的指南经过全体成员的评估和投票,首先通过Delphi电子流程,随后经过全体共识会议。指南根据现有最佳证据提出,目的是为计划进行FMT的医师提供指导,以期支持这种疗法的广泛适用性,探讨与FMT有关的其他事项并促进未来在肠道菌群操作领域的临床研究。共识报告强烈建议建立治疗艰难梭菌感染的FMT中心,并提供技术、标准、管理和实验室相关要求。

关键词：粪菌移植难辨梭状芽孢杆菌感染欧洲共识

在炎性肠病中,核因子-κB受体活化子配体/血清护骨素(RANKL/OPG)被激活而且和个人体质或者骨丢失有关

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世界核心医学期刊文摘（胃肠病学分册） 2005年第8期1卷 40-40页

作者： Moschen A.R Kaser A Enrich B H. tilg 赵天智 Department of Medicine Un iversity Hospital InnsbruckAnichstr 35 6020 Innsbruck Austria.Dr

Background and aims: A substantial proportion of patients with inflammatory bo wel disease (IBD) develops osteopenia and osteoporosis in the course of disease. Recent data from a mouse model of colitis suggest that the receptor activator o f nuclear factor kappa B (RANKL)/osteoprotegerin (OPG) system may be responsible for bone loss. Methods: We investigated the activation state of the RANKL/OPG s ystem and its association with bone loss in human IBD. Plasma levels of OPG and RANKL were correlated with bone mineral density and current IBD therapy. Colonic secretion of OPG and RANKL and cell types responsible for such secretion were d etermined. Results:OPG plasma levels were elevated 2.4-fold in Crohn’s disease (CD) an- d 1.9-fold in ulcerative colitis (UC) whereas soluble RANKL (sRANKL) levels w ere not significantly different in IBD patients compared with healthy controls. High levels of OPG were released from colonic explant cultures (CEC) derived fro m inflamed IBD specimens, and colonic macrophages and dendritic cells costained for OPG. sRANKL levels from CEC were low both in IBD patients and healthy contro ls. Interestingly,increased expression of RANKL was mainly confined to cells in the lamina muscularis. A significant negative correlation was found between OPG plasma levels and femoral neck/lumbar spine bone mineral density. Conclusions: W e have demonstrated that IBD is associated with alterations in the RANKL/OPG sys tem. Applying results from a murine model of colitis associated bone loss, the c onstellation of OPG and sRANKL regulation observed in our study raises the possi bility that RANKL/OPG may contribute to the development of bone loss in IBD.

关键词： RANKL/OPG 炎性肠病护骨素骨丢失结肠炎模型骨矿物质密度骨质减少克罗恩病溃疡性结肠炎骨质疏松