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Oxidative stress in alcohol-related liver disease

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World Journal of Hepatology 2020年第7期12卷 332-349页

作者： Huey K Tan Euan Yates Kristen Lilly Ashwin D Dhanda Hepatology Research Group Institute of Translational and Stratified MedicineFaculty of HealthUniversity of PlymouthPlymouth PL68BUUnited Kingdom South West liver Unit University Hospitals Plymouth NHS TrustPlymouth PL68DHUnited Kingdom Department of Clinical Immunology University Hospitals Plymouth NHS TrustPlymouth PL68DHUnited Kingdom

alcohol consumption is one of the leading causes of the global burden of disease and results in high healthcare and economic *** alcohol misuse leads to alcohol-related liver disease,which is responsible for a significant proportion of alcohol-attributable deaths *** than reducing alcohol consumption,there are currently no effective treatments for alcohol-related liver *** stress refers to an imbalance in the production and elimination of reactive oxygen species and *** plays important roles in several aspects of alcohol-related liver disease ***,we review how chronic alcohol use results in oxidative stress through increased metabolism via the cytochrome P4502E1 system producing reactive oxygen species,acetaldehyde and protein and DNA *** trigger inflammatory signaling pathways within the liver leading to expression of pro-inflammatory mediators causing hepatocyte apoptosis and *** oxygen species exposure also results in mitochondrial stress within hepatocytes causing structural and functional dysregulation of mitochondria and upregulating apoptotic *** is also evidence that oxidative stress as well as the direct effect of alcohol influences epigenetic *** global histone methylation and acetylation and specific histone acetylation inhibits antioxidant responses and promotes expression of key pro-inflammatory *** review highlights aspects of the role of oxidative stress in disease pathogenesis that warrant further study including mitochondrial stress and epigenetic *** understanding of these processes may identify novel targets for therapy.

关键词： alcohol-related liver disease alcoholic hepatitis Oxidative stress Reactive

Genetically predicted fatty liver disease and risk of psychiatric disorders: A mendelian randomization study

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World Journal of Clinical Cases 2024年第14期12卷 2359-2369页

作者： Wei-Ming Xu Hai-Fu Zhang Yong-Hang Feng Shuo-Jun Li Bi-Yun Xie Department of Medicine The First People's Hospital of FuyangHangzhou 311400Zhejiang ProvinceChina Department of Internal Medicine The First People's Hospital of FuyangHangzhou 311400Zhejiang ProvinceChina

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)and alcohol-related liver disease(Ar-LD)constitute the primary forms of chronic liver disease,and their incidence is progressively increasing with changes in lifestyle *** studies have do-cumented a correlation between the occurrence and development of prevalent mental disorders and fatty *** To investigate the correlation between fatty liver and mental disorders,thus ne-cessitating the implementation of a mendelian randomization(MR)study to elu-cidate this *** Data on NAFLD and ArLD were retrieved from the genome-wide association studies catalog,while information on mental disorders,including Alzheimer's disease,schizophrenia,anxiety disorder,attention deficit hyperactivity disorder(ADHD),bipolar disorder,major depressive disorder,multiple personality dis-order,obsessive-compulsive disorder(OCD),post-traumatic stress disorder(PTSD),and schizophrenia was acquired from the psychiatric genomics consor-tium.A two-sample MR method was applied to investigate mediators in signifi-cant *** After excluding weak instrumental variables,a causal relationship was identified between fatty liver disease and the occurrence and development of some psychia-tric ***,the findings indicated that ArLD was associated with a significantly elevated risk of developing ADHD(OR:5.81,95%CI:5.59-6.03,Pliver disease and an increased risk of a broad range of psychiatric disorders,namely bipolar disorder,OCD,and PTSD,highlighting the significance of preven-tive measures against psy

关键词： Non-alcoholic fatty liver disease alcohol-related liver disease Psychiatric disorders Mendelian randomization Single nucleotide polymorphisms

liver regeneration as treatment target for severe alcoholic hepatitis

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World Journal of Gastroenterology 2022年第32期28卷 4557-4573页

作者： Lucija Virovic-Jukic Dominik Ljubas Sanja Stojsavljevic-Shapeski Neven Ljubičić Tajana Filipec Kanizaj Ivana Mikolasevic Ivica Grgurevic Department of Gastroenterology and Hepatology Sisters of Charity University Hospital CenterZagreb 10000Croatia Department of Internal Medicine University of Zagreb School of MedicineZagreb 10000Croatia Department of Internal Medicine University of Zagreb School of Dental MedicineZagreb 10000Croatia Department of Gastroenterology Merkur University HospitalZagreb 10000Croatia Department of Gastroenterology Rijeka University Hospital CenterRijeka 51000Croatia Department of Internal Medicine University of Rijeka School of MedicineRijeka 10000Croatia Department of Gastroenterology Hepatology and Clinical NutritionDubrava University HospitalZagreb 10000Croatia

Severe alcoholic hepatitis(AH)is a distinct entity in the spectrum of alcoholrelated liver disease,with limited treatment options and high *** medical care with corticosteroids in selected patients is the only currently available treatment option,often with poor *** on the insights into the pathogenetic mechanisms of AH,which are mostly obtained from animal studies,several new treatment options are being *** have implicated impaired and deranged liver regeneration processes as one of the culprit mechanisms and a potential therapeutic *** evidence for the beneficial effects of granulocyte colony-stimulating factor(G-CSF)on liver regeneration and immunomodulation in animal models,several human studies investigated its role in the treatment of advanced alcohol-related liver disease and *** to the previously published studies suggesting benefits of G-CSF in the outcomes of patients with severe AH,these effects were not confirmed by a recently published multicenter randomized trial,suggesting that other options should rather be *** cell transplantation represents another option for improving liver regeneration,but evidence for its efficacy in patients with severe AH and advanced alcohol-related liver disease is still very scarce and unconvincing,with established lack of efficacy in patients with compensated *** this review,we summarize the current knowledge on the pathogenesis and experimental therapies targeting liver *** lack of high-quality studies and evidence is a major obstacle in further treatment *** insights into the pathogenesis of not only liver injury,but also liver regeneration processes are mandatory for the development of new treatment options.A reliable experimental model of the pathogenesis of AH and processes involved in liver recovery is still missing,and data obtained from animal studies are essential for future research.

关键词： Severe alcoholic hepatitis alcohol-related liver disease Treatment liver regeneration Granulocyte colony-stimulating factor Stem cell transplantation

liver transplantation and aging

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World Journal of Transplantation 2020年第9期10卷 256-266页

作者： Danko Mikulic Anna Mrzljak Department of Abdominal and Transplant Surgery Merkur University HospitalZagreb 10000Croatia Department of Medicine Merkur University Hospital School of Medicine University of ZagrebZagreb 10000Croatia

An increase in the average life expectancy,paralleled by a demographic shift in the population with end-stage liver disease lies behind the rising demand for liver transplantation(LT)among the *** of the most common indications for LT including hepatocellular carcinoma,alcohol-related liver disease,chronic hepatitis C and non-alcoholic fatty liver disease tend to affect older *** professionals are faced with an increasing demand for LT among elderly patients in an age of organ shortage and it is important that risk and benefits are carefully weighed in order to achieve the optimum use of precious liver grafts.

关键词： liver transplantation Elderly Hepatocellular carcinoma alcohol-related liver disease Non-alcoholic fatty liver disease Hepatitis C virus