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Elafibranor:A promising treatment for alcoholic liver disease,metabolic-associated fatty liver disease,and cholestatic liver disease
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作者 Hang Zhang Xuan Dong +1 位作者 Lei Zhu Fu-Shan Tang 《World Journal of Gastroenterology》 SCIE CAS 2024年第40期4393-4398,共6页
Liver diseases pose a significant threat to human health.Although effective therapeutic agents exist for some liver diseases,there remains a critical need for advancements in research to address the gaps in treatment ... Liver diseases pose a significant threat to human health.Although effective therapeutic agents exist for some liver diseases,there remains a critical need for advancements in research to address the gaps in treatment options and improve patient outcomes.This article reviews the assessment of Elafibranor's effects on liver fibrosis and intestinal barrier function in a mouse model of alcoholic liver disease(ALD),as reported by Koizumi et al in the World Journal of Gastroenterology.We summarize the impact and mechanisms of Elafibranor on ALD,metabolic-associated fatty liver disease,and cholestatic liver disease based on current research.We also explore its potential as a dual agonist of PPARα/δ,which is undergoing Phase III clinical trials for metabolic-associated steatohepatitis.Our goal is to stimulate further investigation into Elafibranor's use for preventing and treating these liver diseases and to provide insights for its clinical application. 展开更多
关键词 Elafibranor Peroxisome proliferator activated receptor liver fibrosis alcoholic liver disease Metabolic-associated fatty liver disease Metabolic-associated steatohepatitis Cholestatic liver disease Primary biliary cholangitis liver diseases
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Peroxisome proliferator-activated receptor agonists:A new hope towards the management of alcoholic liver disease
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作者 Siva Sundara Kumar Durairajan Abhay Kumar Singh Ashok Iyaswamy 《World Journal of Gastroenterology》 SCIE CAS 2024年第35期3965-3971,共7页
In this editorial,we examine a paper by Koizumi et al,on the role of peroxisome proliferator-activated receptor(PPAR)agonists in alcoholic liver disease(ALD).The study determined whether elafibranor protected the inte... In this editorial,we examine a paper by Koizumi et al,on the role of peroxisome proliferator-activated receptor(PPAR)agonists in alcoholic liver disease(ALD).The study determined whether elafibranor protected the intestinal barrier and reduced liver fibrosis in a mouse model of ALD.The study also underlines the role of PPARs in intestinal barrier function and lipid homeostasis,which are both affected by ALD.Effective therapies are necessary for ALD because it is a critical health issue that affects people worldwide.This editorial analyzes the possibility of PPAR agonists as treatments for ALD.As key factors of inflammation and metabolism,PPARs offer multiple methods for managing the complex etiology of ALD.We assess the abilities of PPARα,PPARγ,and PPARβ/δagonists to prevent steatosis,inflammation,and fibrosis due to liver diseases.Recent research carried out in preclinical and clinical settings has shown that PPAR agonists can reduce the severity of liver disease.This editorial discusses the data analyzed and the obstacles,advantages,and mechanisms of action of PPAR agonists for ALD.Further research is needed to understand the efficacy,safety,and mechanisms of PPAR agonists for treating ALD. 展开更多
关键词 alcoholic liver disease Peroxisome proliferator-activated receptors Peroxisome proliferator-activated receptors agonists liver fibrosis INFLAMMATION Metabolic regulation HEPATOPROTECTION
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Clinical differences between alcoholic liver disease and nonalcoholic fatty liver disease 被引量:14
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作者 Nobuyuki Toshikuni Mikihiro Tsutsumi Tomiyasu Arisawa 《World Journal of Gastroenterology》 SCIE CAS 2014年第26期8393-8406,共14页
Alcoholic liver disease(ALD)and nonalcoholic fatty liver disease(NAFLD)are serious health problems worldwide.These two diseases have similar pathological spectra,ranging from simple hepatic steatosis to steatohepatiti... Alcoholic liver disease(ALD)and nonalcoholic fatty liver disease(NAFLD)are serious health problems worldwide.These two diseases have similar pathological spectra,ranging from simple hepatic steatosis to steatohepatitis,liver cirrhosis,and hepatocellular carcinoma.Although most subjects with excessive alcohol or food intake experience simple hepatic steatosis,a small percentage of individuals will develop progressive liver disease.Notably,both ALD and NAFLD are frequently accompanied by extrahepatic complications,including cardiovascular disease and malignancy.The survival of patients with ALD and NAFLD depends on various disease-associated conditions.This review delineates the clinical characteristics and outcomes of patients with ALD and NAFLD by comparing their epidemiology,the factors associated with disease susceptibility and progression,and the predictors and characteristics of outcomes.A comprehensive understanding of the characteristics and outcomes of ALD and NAFLD is imperative in the management of these chronic liver diseases. 展开更多
关键词 alcoholic liver disease Nonalcoholic fatty liver disease Clinical characteristics OUTCOMES Chronic liver disease
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Significance of gut microbiota in alcoholic and non-alcoholic fatty liver diseases 被引量:6
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作者 Satya Priya Sharma Ki Tae Suk Dong Joon Kim 《World Journal of Gastroenterology》 SCIE CAS 2021年第37期6161-6179,共19页
Liver-gut communication is vital in fatty liver diseases,and gut microbes are the key regulators in maintaining liver homeostasis.Chronic alcohol abuse and persistent overnutrition create dysbiosis in gut ecology,whic... Liver-gut communication is vital in fatty liver diseases,and gut microbes are the key regulators in maintaining liver homeostasis.Chronic alcohol abuse and persistent overnutrition create dysbiosis in gut ecology,which can contribute to fatty liver disease.In this review,we discuss the gut microbial compositional changes that occur in alcoholic and nonalcoholic fatty liver diseases and how this gut microbial dysbiosis and its metabolic products are involved in fatty liver disease pathophysiology.We also summarize the new approaches related to gut microbes that might help in the diagnosis and treatment of fatty liver disease. 展开更多
关键词 Fatty liver disease alcoholic fatty liver disease Non-alcoholic fatty liver disease Gut microbiome DYSBIOSIS
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Surgically induced weight loss by gastric bypass improves non alcoholic fatty liver disease in morbid obese patients 被引量:7
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作者 Víctor Vargas Helena Allende +10 位作者 Albert Lecube Maria Teresa Salcedo Juan A Baena-Fustegueras José M Fort Joaquín Rivero Roser Ferrer Roberto Catalán Eva Pardina Santiago Ramón y Cajal Jaime Guardia Julia Peinado-Onsurbe 《World Journal of Hepatology》 CAS 2012年第12期382-388,共7页
AIM: To evaluate the effects of surgical weight loss (Roux-en-Y gastric bypass with a modified Fobi-Capella technique) on non alcoholic fatty liver disease in obese patients.
关键词 Non alcoholic fatty liver disease Bariatric surgery OBESITY Non alcoholic steatohepatitis
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Intestinal virome:An important research direction for alcoholic and nonalcoholic liver diseases
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作者 Yan Li Wen-Cheng Liu Bing Chang 《World Journal of Gastroenterology》 SCIE CAS 2022年第26期3279-3281,共3页
In recent years,the interaction between the gut microflora and liver diseases has attracted much attention.The intestinal microflora is composed of bacteria,archaea,fungi and viruses.There are few studies on the intes... In recent years,the interaction between the gut microflora and liver diseases has attracted much attention.The intestinal microflora is composed of bacteria,archaea,fungi and viruses.There are few studies on the intestinal virome,and whether it has a causal relationship with bacterial changes in the gut is still unclear.However,it is undeniable that the intestinal virome is also a very important portion of the blueprint for the development of liver diseases and the diagnosis and therapeutic modalities in the future. 展开更多
关键词 alcoholic fatty liver disease Nonalcoholic fatty liver disease Fatty liver disease Gut microbiome Intestinal virome
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Expression of lipopolysaccharide binding protein and its receptor CD14 in experimental alcoholic liver disease 被引量:14
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作者 Guo-Qing Zuo~1 Jian-Ping Gong~2 Chang-An Liu~2 Shen-Wei Li~2 Xin-Chuan Wu~2 Kang Yang~2 Yue Li~2 1 Department of Digestive Disease2 Department of General Surgery,Second College of Clinical Medicine &the Second Affiliated Hospital,Chongqing University of Medical Sciences,Chongqing 400010,China 《World Journal of Gastroenterology》 SCIE CAS CSCD 2001年第6期836-840,共5页
AIM: To evaluate the relationship between the expression of lipopolysaccharides (LPS) binding protein (LBP) and CD14 mRNA and the severity of liver injury in alcohol-fed rats. METHODS: Twenty Wistar rats were divided ... AIM: To evaluate the relationship between the expression of lipopolysaccharides (LPS) binding protein (LBP) and CD14 mRNA and the severity of liver injury in alcohol-fed rats. METHODS: Twenty Wistar rats were divided into two groups:ethanol-fed group (group E) and control group (group C). Group E was fed with ethanol(5-12 g x kg(-1) x d(-1)) and group C received dextrose instead of ethanol. Rats of the two groups were sacrificed at 4 weeks and 8 weeks. Levels of endotoxin and alanine transaminase (ALT) in blood were measured, and liver pathology was observed under light and electronic microscopy. Expressions of LBP and CD14 mRNA in liver tissues were determined by RT-PCR analysis. RESULTS: Plasma endotoxin levels were increased more significantly in group E(129+/-21) ng x L(-1) and (187+/-35) ng x L(-1) at 4 and 8 wk than in control rats(48+/-9) ng x L(-1) and (53+/-11) ng x L(-1), respectively (P【0.05). Mean values of plasma ALT levels were (1867+/-250) nkat x L(-1) and (2450+/-367) nkat x L(-1) in Group E. The values were increased more dramatically in ethanol-fed rats than in Group C after 4 and 8 weeks. In liver section from ethanol-fed rats, there were marked pathological changes (steatosis, cell infiltration and necrosis). In ethanol-fed rats, ethanol administration led to a significant increase in LBP and CD14 mRNA levels compared with the control group (P【0.05). CONCLUSION: Ethanol administration led to a significant increase in endotoxin levels in serum and LBP and CD14 mRNA expressions in liver tissues. The increase of LBP and CD14 mRNA expression might wake the liver more sensitive to endotoxin and liver injury. 展开更多
关键词 Acute-Phase Proteins Gene Expression Membrane Glycoproteins Animals Antigens CD14 Carrier Proteins Female liver liver diseases alcoholic RNA Messenger RATS Rats Wistar Research Support Non-U.S. Gov't Severity of Illness Index
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Quantitative analysis of transforming growth factor beta 1 mRNA in patients with alcoholic liver disease 被引量:21
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作者 Wei-Xing Chen You-Ming Li Chao-Hui Yu Wei-Min Cai Min Zheng Feng-Chen,Department of Gastroenterology, The First Affiliated Hospital,Medical College of Zhejiang University,Hangzhou 310003,Zhejiang Province,China 《World Journal of Gastroenterology》 SCIE CAS CSCD 2002年第2期379-381,共3页
AIM: To investigate the expression of the transforming growth factor beta 1(TGF-beta 1) mRNA in different stages of alcoholic liver disease (ALD) and its clinical value. METHODS: One hundred and seven male alcoholics ... AIM: To investigate the expression of the transforming growth factor beta 1(TGF-beta 1) mRNA in different stages of alcoholic liver disease (ALD) and its clinical value. METHODS: One hundred and seven male alcoholics were grouped by clinical findings into four groups: alcohol abusers without liver impairment (n =22), alcoholic steatosis (n =30); alcoholic hepatitis (n=31); and alcoholic cirrhosis(n=24). Using peripheral blood mononuclear cells (PBMC) as samples the gene expression of TGF-beta 1 was examined quantitatively by reverse transcription polymerase chain reaction (RT-PCR) and dot blot. There are 34 healthy subjects served as control. RESULTS: The expression of TGF-beta 1 from all ALD patients was significantly greater than that in controls (1.320 +/- 1.162 vs 0.808 +/- 0.276, P【0.001). The differences of the expressions were significant between the patients from each groups (alcoholic steatosis, alcoholic hepatitis and alcoholic cirrhosis) and the controls (1.168 +/- 0.852, 1.462 +/- 1.657, 1.329 +/- 0.610 vs 0.808 +/- 0.276, P【0.050). No significant differences of TGF -beta 1 mRNA expression were observed between alcohol abusers without liver impairment and controls. The expressions in patients with alcoholic hepatitis and alcoholic cirrhosis were significantly greater than that in alcohol abusers respectively (1.462 +/- 1.657, 1.329 +/- 0.610 vs 0.841 +/- 0.706, P【0.050). No significant differences of TGF-beta 1 mRNA expression were observed between alcoholic fatty liver men and alcohol abusers. CONCLUSION: TGF-beta 1 expression level can be a risk factor for alcoholic liver disease and might be related to the inflammatory activity and fibrosis of the liver in patients. 展开更多
关键词 Humans liver diseases alcoholic MALE RNA Messenger Transforming Growth Factor beta
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Detection of alcoholic liver disease 被引量:13
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作者 Harriet Gordon 《World Journal of Gastroenterology》 SCIE CAS CSCD 2001年第3期297-302,共6页
INTRODUCTIONAlcohol has been used in society over centuries and all over the world for its mood-lifting properties and taste. It is probably ,however ,the commonest drug of abuse world-wide and unfortunately causes co... INTRODUCTIONAlcohol has been used in society over centuries and all over the world for its mood-lifting properties and taste. It is probably ,however ,the commonest drug of abuse world-wide and unfortunately causes considerable morbidity, mortality and social disruption .In 1990 the cost tl the USA was more than $ 100 billion and 100 000 lives.The relationship between alcohol and mankind is well documented from the earliest tines . 展开更多
关键词 Biological Markers Humans liver diseases alcoholic
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Therapy for alcoholic liver disease 被引量:13
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作者 Maryconi M Jaurigue Mitchell S Cappell 《World Journal of Gastroenterology》 SCIE CAS 2014年第9期2143-2158,共16页
Alcoholism results in about 2.5 million deaths annually worldwide, representing 4% of all mortality. Although alcoholism is associated with more than 60 diseases, most mortality from alcoholism results from alcoholic ... Alcoholism results in about 2.5 million deaths annually worldwide, representing 4% of all mortality. Although alcoholism is associated with more than 60 diseases, most mortality from alcoholism results from alcoholic liver disease (ALD). ALD includes alcoholic steatosis, alcoholic hepatitis, and alcoholic cirrhosis, in order of increasing severity. Important scoring systems of ALD severity include: Child-Pugh, a semi-quantitative scoring system useful to roughly characterize clinical severity; model for end-stage liver disease, a quantitative, objective scoring system used for prognostication and prioritization for liver transplantation; and discriminant function, used to determine whether to administer corticosteroids for alcoholic hepatitis. Abstinence is the cornerstone of ALD therapy. Psychotherapies, including twelve-step facilitation therapy, cognitive-behavioral therapy, and motivational enhancement therapy, help support abstinence. Disulfiram decreases alcohol consumption by causing unpleasant sensations after drinking alcohol from accumulation of acetaldehyde in serum, but disulfiram can be hepatotoxic. Adjunctive pharmacotherapies to reduce alcohol consumption include naltrexone, acamprosate, and baclofen. Nutritional therapy helps reverse muscle wasting, weight loss, vitamin deficiencies, and trace element deficiencies associated with ALD. Although reduced protein intake was previously recommended for advanced ALD to prevent hepatic encephalopathy, a diet containing 1.2-1.5 g of protein/kg per day is currently recommended to prevent muscle wasting. Corticosteroids are first-line therapy for severe alcoholic hepatitis (discriminant function &#x02265; 32), but proof of their efficacy in decreasing mortality remains elusive. Pentoxifylline is an alternative therapy. Complications of advanced ALD include ascites, spontaneous bacterial peritonitis, esophageal variceal bleeding, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, and portopulmonary hypertension. Alcoholic cirrhotics have increased risk of developing hepatomas. Liver transplantation is the ultimate therapy for severe ALD, but generally requires 6 mo of proven abstinence for eligibility. Alcoholic cirrhotics who maintain abstinence generally have a relatively favorable prognosis after liver transplantation. 展开更多
关键词 alcoholic liver disease alcoholic steatosis alcoholic hepatitis alcoholic cirrhosis ALCOHOLISM liver disease CORTICOSTEROIDS PENTOXIFYLLINE liver transplantation
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Meta-analysis reveals up-regulation of cholesterol processes in non-alcoholic and down-regulation in alcoholic fatty liver disease 被引量:8
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作者 Wasco Wruck James Adjaye 《World Journal of Hepatology》 CAS 2017年第8期443-454,共12页
AIM To compare transcriptomes of non-alcoholic fatty liver disease(NAFLD) and alcoholic liver disease(ALD) in a meta-analysis of liver biopsies.METHODS Employing transcriptome data from patient liver biopsies retrieve... AIM To compare transcriptomes of non-alcoholic fatty liver disease(NAFLD) and alcoholic liver disease(ALD) in a meta-analysis of liver biopsies.METHODS Employing transcriptome data from patient liver biopsies retrieved from several public repositories we performed a meta-analysis comparing ALD and NAFLD.RESULTS We observed predominating commonalities at the transcriptome level between ALD and NAFLD,most prominently numerous down-regulated metabolic pathways and cytochrome-related pathways and a few up-regulated pathways which include ECM-receptor interaction,phagosome and lysosome.However some pathways were regulated in opposite directions in ALD and NAFLD,for example,glycolysis was down-regulated in ALD and up-regulated in NAFLD.Interestingly,we found rate-limiting genes such as HMGCR,SQLE and CYP7A1 which are associated with cholesterol processes adversely regulated between ALD(down-regulated) and NAFLD(up-regulated).We propose that similar phenotypes in both diseases may be due to a lower level of the enzyme CYP7A1 compared to the cholesterol synthesis enzymes HMGCR and SQLE.Additionally,we provide a compendium of comparative KEGG pathways regulation in ALD and NAFLD.CONCLUSION Our finding of adversely regulated cholesterol processes in ALD and NAFLD draws the focus to regulation of cholesterol secretion into bile.Thus,it will be interesting to further investigate CYP7A1-mediated cholesterol secretion into bile-also as possible drug targets.The list of potential novel biomarkers may assist differential diagnosis of ALD and NAFLD. 展开更多
关键词 Non-alcoholic fatty liver disease alcoholic liver disease cholesterol BILE Alcohol dehydrogenase CYP7A1
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Liver transplantation for alcoholic liver disease 被引量:6
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作者 Vibha Varma Kerry Webb Darius F Mirza 《World Journal of Gastroenterology》 SCIE CAS CSCD 2010年第35期4377-4393,共17页
Alcoholic liver disease(ALD) is the second commonest indication for liver transplantation after viral hepatitis in the United States and Europe.Controversies surround the indications and allocation of scarce and expen... Alcoholic liver disease(ALD) is the second commonest indication for liver transplantation after viral hepatitis in the United States and Europe.Controversies surround the indications and allocation of scarce and expensive resource for this so called self inflicted disease.Controversies stem from the apprehension that alcoholic recipients are likely to relapse and cause damage to the graft.There is a need to select those candidates with lower risk for relapse with the available predictive factors and scores.Substance abuse specialist and psychiatrists are mandatory in the pre-transplant evaluation and in the post-transplant follow-up.There is conflicting evidence to support a fixed period of pretransplant abstinence,although most units do follow this.Alcoholic hepatitis(AH) continues to be a contraindication for transplantation,however there is a need for further research in this f ield as a subset of patients with AH who do not respond to medical treatment,have high early mortality and could benefit from transplantation.One year,3-year,and 5-year survival post-transplant is similar for both ALD and non-ALD recipients.The incidence of post-transplant rejection and retransplantation is also similar to other recipients.ALD with viral hepatitis especially hepatitis C virus leads to a more aggressive liver disease with early presentation for transplantation.ALD patients are more prone to develop de-novo malignancy;this is attributed to the long term effect of alcohol,tobacco combined with immunosuppression.Post-transplant surveillance is important to detect early relapse to alcoholism,presence of de-novo malignancy and treat the same adequately. 展开更多
关键词 alcoholic liver disease Orthotopic liver transplantation Pre-transplant abstine nce Acute alcoholic hepatitis De-novo malignancy Predictors of relapse Hepatitis C virus
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Fibronectin: Functional character and role in alcoholic liver disease 被引量:5
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作者 Razia S Aziz-Seible Carol A Casey 《World Journal of Gastroenterology》 SCIE CAS CSCD 2011年第20期2482-2499,共18页
Fibronectins are adhesive glycoproteins that can be found in tissue matrices and circulating in various fluids of the body. The variable composition of fibronectin molecules facilitates a diversity of interactions wit... Fibronectins are adhesive glycoproteins that can be found in tissue matrices and circulating in various fluids of the body. The variable composition of fibronectin molecules facilitates a diversity of interactions with cell surface receptors that suggest a role for these proteins beyond the structural considerations of the extracellular matrix. These interactions implicate fibronectin in the regulation of mechanisms that also determine cell behavior and activity. The two major forms, plasma fibronectin (pFn) and cellular fibronectin (cFn), exist as balanced amounts under normal physiological conditions. However, during injury and/or disease, tissue and circulating levels of cFn become disproportionately elevated. The accumulating cFn, in addition to being a consequence of prolonged tissue damage, may in factstimulate cellular events that promote further damage. In this review, we summarize what is known regarding such interactions between fibronectin and cells that may influence the biological response to injury. We elaborate on the effects of cFn in the liver, specifically under a condition of chronic alcohol-induced injury. Studies have revealed that chronic alcohol consumption stimulates excess production of cFn by sinusoidal endothelial cells and hepatic stellate cells while impairing its clearance by other cell types resulting in the build up of this glycoprotein throughout the liver and its consequent increased availability to influence cellular activity that could promote the development of alcoholic liver disease. We describe recent findings by our laboratory that support a plausible role for cFn in the promotion of liver injury under a condition of chronic alcohol abuse and the implications of cFn stimulation on the pathogenesis of alcoholic liver disease. These findings suggest an effect of cFn in regulating cell behavior in the alcohol-injured liver that is worth further characterizing not only to gain a more comprehensive understanding of the role this reactive glycoprotein plays in the progression of injury but also for the insight further studies could provide towards the development of novel therapies for alcoholic liver disease. 展开更多
关键词 FIBRONECTIN liver disease alcoholic liver disease ENDOCYTOSIS Cellular fibronectin
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Experimental models of metabolic and alcoholic fatty liver disease 被引量:4
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作者 Delfin Gerard Buyco Jasmin Martin +3 位作者 Sookyoung Jeon Royce Hooks Chelsea Lin Rotonya Carr 《World Journal of Gastroenterology》 SCIE CAS 2021年第1期1-18,共18页
Non-alcoholic fatty liver disease(NAFLD)is a multi-systemic disease that is considered the hepatic manifestation of metabolic syndrome(MetS).Because alcohol consumption in NAFLD patients is common,there is a significa... Non-alcoholic fatty liver disease(NAFLD)is a multi-systemic disease that is considered the hepatic manifestation of metabolic syndrome(MetS).Because alcohol consumption in NAFLD patients is common,there is a significant overlap in the pathogenesis of NAFLD and alcoholic liver disease(ALD).Indeed,MetS also significantly contributes to liver injury in ALD patients.This“syndrome of metabolic and alcoholic steatohepatitis”(SMASH)is thus expected to be a more prevalent presentation in liver patients,as the obesity epidemic continues.Several pre-clinical experimental models that couple alcohol consumption with NAFLDinducing diet or genetic obesity have been developed to better understand the pathogenic mechanisms of SMASH.These models indicate that concomitant MetS and alcohol contribute to lipid dysregulation,oxidative stress,and the induction of innate immune response.There are significant limitations in the applicability of these models to human disease,such as the ability to induce advanced liver injury or replicate patterns in human food/alcohol consumption.Thus,there remains a need to develop models that accurately replicate patterns of obesogenic diet and alcohol consumption in SMASH patients. 展开更多
关键词 Non-alcoholic fatty liver disease alcoholic liver disease Non-alcoholic steatohepatitis Animal models Insulin resistance Oxidative stress
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phosphatase and tensin homolog is a differential diagnostic marker between nonalcoholic and alcoholic fatty liver disease 被引量:2
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作者 Andrea Sanchez-Pareja Sophie Clément +4 位作者 Marion Peyrou Laurent Spahr Francesco Negro Laura Rubbia-Brandt Michelangelo Foti 《World Journal of Gastroenterology》 SCIE CAS 2016年第14期3735-3745,共11页
AIM: To investigate the protein expression of phosphatase and tensin homolog (PTEN) in human liver biopsies of patients with alcoholic and non-alcoholic liver disease.METHODS: PTEN protein expression was assessed by i... AIM: To investigate the protein expression of phosphatase and tensin homolog (PTEN) in human liver biopsies of patients with alcoholic and non-alcoholic liver disease.METHODS: PTEN protein expression was assessed by immunohistochemistry in formalin-fixed, paraffin-embedded liver sections of patients with non-alcoholic fatty liver disease (NAFLD) (n = 44) or alcoholic liver disease (ALD) (n = 25). Liver resections obtained from 3 healthy subjects candidate for partial liver donation served as controls. Histological evaluations were performed by two experienced pathologists, and diagnoses established based on international criteria. The intensity of the PTEN staining in nuclei was compared between steatotic and non-steatotic areas of each liver fragment analyzed. For each liver specimen, the antibody-stained sections were examined and scored blindly by three independent observers, who were unaware of the patients&#x02019; clinical history.RESULTS: In healthy individuals, PTEN immunostaining was intense in both the cytoplasm and nuclei of all hepatocytes. However, PTEN was strongly downregulated in both the nucleus and the cytoplasm of hepatocytes from steatotic areas in patients with NAFLD, independently of the disease stage. In contrast, no changes in PTEN protein expression were observed in patients with ALD, regardless of the presence of steatosis or the stage of the disease. The degree of PTEN downregulation in hepatocytes of patients with NAFLD correlated with the percentage of steatosis (r = 0.3061, P = 0.0459) and the BMI (r = 0.4268, P = 0.0043). Hovewer, in patients with ALD, PTEN expression was not correlated with the percentage of steatosis with or without obesity as a confounding factor (P = 0.5574). Finally, PTEN expression level in steatotic areas of ALD patients was significantly different from that seen in steatotic areas of NAFLD patients (P &#x0003c; 0.0001).CONCLUSION: PTEN protein expression is downregulated early in NAFLD, but not in ALD. PTEN immunohistochemical detection could help in the differential diagnosis of NAFLD and ALD. 展开更多
关键词 Fibrosis Phosphatase and tensin homolog STEATOSIS Non-alcoholic fatty liver disease Nonalcoholic steatohepatitis alcoholic liver disease Cirrhosis Hepatocellular carcinoma
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Characteristics of alcoholic liver disease and predictive factors for mortality of patients with alcoholic cirrhosis 被引量:2
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作者 Yan-Di Xie Bo Feng +1 位作者 Yan Gao Lai Wei 《Hepatobiliary & Pancreatic Diseases International》 SCIE CAS 2013年第6期594-601,共8页
BACKGROUND:Alcoholic liver disease is one of the major chronic liver diseases worldwide.The aim of the study was to describe the clinical characteristics of alcoholic liver disease and to compare the predictive values... BACKGROUND:Alcoholic liver disease is one of the major chronic liver diseases worldwide.The aim of the study was to describe the clinical characteristics of alcoholic liver disease and to compare the predictive values of biochemical parameters,complications,Child-Turcotte-Pugh score,model for end-stage liver disease(MELD)score and discriminant function score for the mortality of in-hospital or 3-month after discharge of patients with alcoholic cirrhosis(AC).METHODS:A retrospective record review and statistical analysis were performed on 205 consecutive patients with the discharge diagnosis of alcoholic liver disease.Three models were used to predict the mortality of patients with AC.The number of variceal hemorrhage,infection,hepatic encephalopathy and hepatocellular carcinoma was analyzed as"numbers of complications".Model 1 consisted of creatinine,white blood cell count,international normalized ratio and"numbers of complications".Model 2 consisted of MELD score.Model 3included"numbers of complications"and MELD score.RESULTS:The risk of developing AC was significant for patients with alcohol consumption of higher than 80 g/d(OR=2.807,P【0.050)and drinking duration of longer than 10 years(OR=3.429,P【0.028).The area under curve for predicting inhospital mortality of models 1,2 and 3 was 0.950,0.886 and 0.911(all P【0.001),respectively.The area under curve for predicting the 3-month mortality of models 1,2 and 3 was 0.867,0.878 and0.893(all P【0.001),respectively.CONCLUSIONS:There is a dose-dependent relationship between alcohol consumption and the risk of developing AC.MELD score has a better predictive value than Child-TurcottePugh or discriminant function score for patients with AC,and model 1 or 3 is better than model 2. 展开更多
关键词 alcoholic liver disease model for end-stage liver disease MORTALITY prognostic factors risk factors
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Fractionation of gamma-glutamyltransferase in patients with nonalcoholic fatty liver disease and alcoholic liver disease 被引量:2
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作者 Shigeo Sueyoshi Setsu Sawai +5 位作者 Mamoru Satoh Masanori Seimiya Kazuyuki Sogawa Atsushi Fukumura Mikihiro Tsutsumi Fumio Nomura 《World Journal of Hepatology》 CAS 2016年第36期1610-1616,共7页
AIM To assess how serum gamma-glutamyltransferase(GGT) fractions vary in patients with alcoholic liver disease(ALD) and non-alcoholic fatty liver disease(NAFLD). METHODS Serum samples were obtained from 14 patients wi... AIM To assess how serum gamma-glutamyltransferase(GGT) fractions vary in patients with alcoholic liver disease(ALD) and non-alcoholic fatty liver disease(NAFLD). METHODS Serum samples were obtained from 14 patients with biopsy-proven alcoholic liver diseases and 9 patients with biopsy proven non-alcoholic fatty liver disease. In addition to these biopsy-proven cases, 16 obese(body mass index > 25) patients without any history of alcohol consumption but with a fatty liver on ultrasound examination and with elevated GGT were included for an additional analysis. Serum GGT fractionation was conducted by high-performance gel filtration liquid chromatography and was separated into the four fractions, big-GGT, medium-GGT, small-GGT(s-GGT), and free-GGT(f-GGT).RESULTS The results were expressed as a ratio of each fraction including the total GGT(t-GGT). The s-GGT/t-GGT ratioswere lowest for the control group and highest for the ALD group. The differences between the control and NAFLD groups and also between the NAFLD and ALD groups were statistically significant. In contrast, the f-GGT/t-GGT ratios were highest in the control group and lowest in the ALD group, with the differences being statistically significant. As a result, the s-GGT/f-GGT ratios were markedly increased in the NAFLD group as compared with the control group. The increase of the s-GGT/t-GGT ratios, the decrease of the f-GGT/t-GGT ratios, and the increase of s-GGT/F-GGT ratios as compared with the control group subjects were also found in obese patients with clinically diagnosed fatty change of the liver.CONCLUSION Serum GGT fractionation by high-performance gel filtration liquid chromatography is potentially useful for the differential diagnosis of ALD and NAFLD. 展开更多
关键词 GAMMA-GLUTAMYLTRANSFERASE f-GGT/t-GGT ratios alcoholic liver disease Non-alcoholic fatty liver disease Gel filtration liquid chromatography
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Alcoholism and alcoholic liver disease: focusing on epidemiological investigation in Asia 被引量:2
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作者 You-Ming Li Hangzhou, China Department of Gastroenterology, First Affiliated Hos- pital, Zhejiang University School of Medicine, Hangzhou 310003, China 《Hepatobiliary & Pancreatic Diseases International》 SCIE CAS 2005年第2期170-172,共3页
关键词 ALDH Alcoholism and alcoholic liver disease
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Predicting utility of a model for end stage liver disease in alcoholic liver disease 被引量:1
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作者 Aspasia S Soultati Spyridon P Dourakis +3 位作者 Alexandra Alexopoulou Melanie Deutsch Larissa Vasilieva Athanasios J Archimandritis 《World Journal of Gastroenterology》 SCIE CAS CSCD 2006年第25期4020-4025,共6页
AIM: To validate the statistic utility of both the Maddrey Discriminant Function score and the Model for End-Stage Liver Disease as predictors of short term (30 d and 90 d) mortality in patients with alcoholic hepa... AIM: To validate the statistic utility of both the Maddrey Discriminant Function score and the Model for End-Stage Liver Disease as predictors of short term (30 d and 90 d) mortality in patients with alcoholic hepatitis and to assess prognostic factors among clinical characteristics and laboratory variables of patients with alcoholic hepatitis. METHODS: Thirty-four patients with the diagnosis of alcoholic hepatitis admitted to Hippokration University Hospital of Athens from 2000 to 2005 were assessed in the current retrospective study and a statistical analysis was conducted. RESULTS: 30- and 90-d mortality rates were reported at 5.9% (2/34) and 14.7% (5/34), respectively. Significant correlation was demonstrated for the Model for End- Stage Liver Disease (P30 = 0.094, P90 = 0.046) and the Maddrey Discriminant Function score (P30 = 0.033, P90 = 0.038) with 30- and 90-d mortality whereas a significant association was also established for alanine aminotrans- ferase (P = 0.057), fibrin degradation products (P = 0.048) and C-reactive protein (P = 0.067) with 90-d mortality. For 30-d mortality the Area Under the Curve was 0.969 (95%CI: 0.902-1.036, P = 0.028) for the Model for End-Stage Liver Disease score and 0.984 (95%CI: 0.942-1.027, P = 0.023) for the Maddrey Discriminant Function score with the optimal cut off point of 30.5 (sensitivity 1, specificity 0.937) and 108.68 (sensitivity 1, specificity 0.969), respectively. Accordingly, for 90-d mortality the Area Under the Curve was 0.762 (95%CI: 0.559-0.965, P = 0.065) for the Model for End-Stage Liver Disease score and 0.752 (95%CI: 0.465-1.038, P = 0.076) for the Maddrey Discriminant Function score with the optimal cut off point of 19 (sensitivity 0.6, specificity 0.6) and 92 (sensitivity 0.6, specificity 0.946), respectively. The observed Kaplan Meier survival rates for different score-categories were compared with logrank tests and higher score values were correlated with a lower survival. CONCLUSION: Equivalency of the Model for End-Stage Liver Disease and the Maddrey Discriminant Function score is implied by the current study, verified by the plotted Receiver Operative Curves and the estimated survival rates. A statistically significant utility of C-reactive protein, fibrin degradation products and alanine aminotransferase as independent predictors of 90-d mortality has also been verified. 展开更多
关键词 alcoholic liver disease alcoholic hepatitis Maddrey discriminant function score Model for end-stage liver disease score
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Diagnosis of alcoholic liver disease 被引量:29
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作者 Cara Torruellas Samuel W French Valentina Medici 《World Journal of Gastroenterology》 SCIE CAS 2014年第33期11684-11699,共16页
Alcohol is a hepatotoxin that is commonly consumed worldwide and is associated with a spectrum of liver injury including simple steatosis or fatty liver, alcoholic hepatitis, fibrosis, and cirrhosis. Alcoholic liver d... Alcohol is a hepatotoxin that is commonly consumed worldwide and is associated with a spectrum of liver injury including simple steatosis or fatty liver, alcoholic hepatitis, fibrosis, and cirrhosis. Alcoholic liver disease(ALD) is a general term used to refer to this spectrum of alcohol-related liver injuries. Excessive or harmful alcohol use is ranked as one of the top five risk factors for death and disability globally and results in 2.5 million deaths and 69.4 million annual disability adjusted life years. All patients who present with clinical features of hepatitis or chronic liver disease or who have elevated serum elevated transaminase levels should be screened for an alcohol use disorder. The diagnosis of ALD can generally be made based on history, clinical and laboratory findings. However, the diagnosis of ALD can be clinically challenging as there is no single diagnostic test that confirms the diagnosis and patients may not be forthcoming about their degree of alcohol consumption. In addition, clinical findings may be absent or minimal in early ALD characterized by hepatic steatosis. Typical laboratory findings in ALD include transaminase levels with aspartate aminotransferase greater than alanine aminotransferase as well as increased mean cor-puscular volume, gamma-glutamyltranspeptidase, and IgA to IgG ratio. In unclear cases, the diagnosis can be supported by imaging and liver biopsy. The histological features of ALD can ultimately define the diagnosis according to the typical presence and distribution of hepatic steatosis, inflammation, and Mallory-Denk bodies. Because of the potential reversible nature of ALD with sobriety, regular screening of the general population and early diagnosis are essential. 展开更多
关键词 alcoholic liver disease DIAGNOSIS Alcohol screening HISTOLOGY Mallory-Denk bodies PROGNOSIS
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