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Pathogenesis of non-alcoholic fatty liver disease in children and adolescence: From “two hit theory” to “multiple hit model” 被引量:114
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作者 Yan-Lan Fang Hong Chen +1 位作者 Chun-Lin Wang Li Liang 《World Journal of Gastroenterology》 SCIE CAS 2018年第27期2974-2983,共10页
Nonalcoholic fatty liver disease(NAFLD) has become the dominant form of chronic liver disease in children and adolescents with the increasing prevalence of obesity worldwide. NAFLD represents a wide spectrum of condit... Nonalcoholic fatty liver disease(NAFLD) has become the dominant form of chronic liver disease in children and adolescents with the increasing prevalence of obesity worldwide. NAFLD represents a wide spectrum of conditions, ranging from fatty liver-which generally follows a benign, non-progressive clinical course-to non-alcoholic steatohepatitis, a subset of NAFLD that may progress to cirrhosis and end-stage liver disease or liver carcinoma. The underlying pathophysiological mechanism of "pediatric" NAFLD remains unclear, although it is strongly associated with obesity and insulin resistance. In this review we provide a general overview on the current understanding of NAFLD in children and adolescents, which underpins practice, enabling early diagnosis and appropriate therapeutic intervention for this life-threatening liver disease. 展开更多
关键词 non-alcoholic STEATOHEPATITIS CHILDREN Adolescents PATHOGENESIS nonalcoholic fatty liver disease
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Sodium butyrate attenuates high-fat diet-induced steatohepatitis in mice by improving gut microbiota and gastrointestinal barrier 被引量:85
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作者 Da Zhou Qin Pan +6 位作者 Feng-Zhi Xin Rui-Nan Zhang Chong-Xin He Guang-Yu Chen Chang Liu Yuan-Wen Chen Jian-Gao Fan 《World Journal of Gastroenterology》 SCIE CAS 2017年第1期60-75,共16页
AIM To investigate whether gut microbiota metabolite sodium butyrate (NaB) is an effective substance for attenuating non-alcoholic fatty liver disease (NAFLD) and the internal mechanisms. METHODS Male C57BL/6J mice we... AIM To investigate whether gut microbiota metabolite sodium butyrate (NaB) is an effective substance for attenuating non-alcoholic fatty liver disease (NAFLD) and the internal mechanisms. METHODS Male C57BL/6J mice were divided into three groups, normal control were fed standard chow and model group were fed a high-fat diet (HFD) for 16 wk, the intervention group were fed HFD for 16 wk and treated with NaB for 8 wk. Gut microbiota from each group were detected at baseline and at 16 wk, liver histology were evaluated and gastrointestinal barrier indicator such as zonula occluden-1 (ZO-1) were detected by immunohistochemistry and realtime-PCR, further serum or liver endotoxin were determined by ELISA and inflammation-or metabolism-associated genes were quantified by real-time PCR. RESULTS NaB corrected the HFD-induced gut microbiota imbalance in mice, while it considerably elevated the abundances of the beneficial bacteria Christensenellaceae, Blautia and Lactobacillus. These bacteria can produce butyric acid in what seems like a virtuous circle. And butyrate restored HFD induced intestinal mucosa damage, increased the expression of ZO-1 in small intestine, further decreased the levels of gut endotoxin in serum and liver compared with HF group. Endotoxin-associated genes such as TLR4 and Myd88, pro-inflammation genes such as MCP-1, TNF-alpha, IL-1, IL-2, IL-6 and IFN-gamma in liver or epididymal fat were obviously downregulated after NaB intervention. Liver inflammation and fat accumulation were ameliorated, the levels of TG and cholesterol in liver were decreased after NaB intervention, NAS score was significantly decreased, metabolic indices such as FBG and HOMA-IR and liver function indicators ALT and AST were improved compared with HF group. CONCLUSION NaB may restore the dysbiosis of gut microbiota to attenuate steatohepatitis, which is suggested to be a potential gut microbiota modulator and therapeutic substance for NAFLD. 展开更多
关键词 non-alcoholic fatty liver disease Sodium butyrate Gut microbiota Gastrointestinal barrier ENDOTOXIN
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Pathogenesis and management issues for non-alcoholic fatty liver disease 被引量:75
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作者 Marko Duvnjak Ivan Leroti +3 位作者 Neven Bari Vedran Tomai Lucija Virovi Juki Vedran Velagi 《World Journal of Gastroenterology》 SCIE CAS CSCD 2007年第34期4539-4550,共12页
Nonalcoholic fatty liver disease (NAFLD) has, although it is a very common disorder, only relatively recently gained broader interest among physicians and scientists. Fatty liver has been documented in up to 10 to 15 ... Nonalcoholic fatty liver disease (NAFLD) has, although it is a very common disorder, only relatively recently gained broader interest among physicians and scientists. Fatty liver has been documented in up to 10 to 15 percent of normal individuals and 70 to 80 percent of obese individuals. Although the pathophysiology of NAFLD is still subject to intensive research, several players and mechanisms have been suggested based on the substantial evidence. Excessive hepatocyte triglyceride accumulation resulting from insulin resistance is the first step in the proposed 'two hit' model of the pathogenesis of NAFLD. Oxidative stress resulting from mitochondrial fatty acids oxidation, NF-κB-dependent inflammatory cytokine expression and adipocytokines are all considered to be the potential factors causing second hits which lead to hepatocyte injury, inflammation and fibrosis. Although it was initially believed that NAFLD is a completely benign disorder, histologic follow-up studies have showed that fibrosis progression occurs in about a third of patients. A small number of patients with NAFLD eventually ends up with end-stage liver disease and even hepatocellular carcinoma. Although liver biopsy is currently the only way to confirm the NAFLD diagnosis and distinguish between fatty liver alone and NASH, no guidelines or firm recommendations can still be made as for when and in whom it is necessary. Increased physical activity, gradual weight reduction and in selected cases bariatric surgery remain the mainstay of NAFLD therapy. Studies with pharmacologic agents are showing promising results, but available data are still insufficient to make specific recommendations; their use therefore remains highly individual. 展开更多
关键词 non-alcoholic fatty liver disease METABOLIC
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非酒精性脂肪肝与代谢综合征关系的研究 被引量:74
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作者 颜红梅 高鑫 +5 位作者 刘蒙 顾迁 张斌 李湘 高键 赵耐青 《中国糖尿病杂志》 CAS CSCD 北大核心 2006年第5期326-328,共3页
目的分析无糖尿病(DM)史的非酒精性脂肪性肝(NAFL)患者糖代谢异常及代谢综合征(MS)的伴随情况,探讨NAFL与MS的关系。方法测量NAFL组(118例)和对照组(56例)的形体参数、血压、血脂谱、OGTT等,MS采用NCEP-ATPⅢ定义。结果NAFL组糖代谢异... 目的分析无糖尿病(DM)史的非酒精性脂肪性肝(NAFL)患者糖代谢异常及代谢综合征(MS)的伴随情况,探讨NAFL与MS的关系。方法测量NAFL组(118例)和对照组(56例)的形体参数、血压、血脂谱、OGTT等,MS采用NCEP-ATPⅢ定义。结果NAFL组糖代谢异常的比率达43·2%,明显高于对照组12·5%(P<0·01)。NAFL组中MS伴有率明显高于对照组(31·4%vs5·4%,P=0·000)。Logistic回归分析显示2hPG、NAFL、肥胖家族史是MS的独立危险因素。以NAFL取代MS五个组分中的任何一个后,与原诊断定义相比一致性均很高(Kappa值均>0·6,P<0·0001)。结论无DM病史的NAFL患者糖代谢异常的比率、MS的伴有率明显增高。NAFL可以作为MS组成成分之一。 展开更多
关键词 非酒精性脂肪肝 糖代谢异常 代谢综合征
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Gut microbiota dysbiosis in patients with nonalcoholic fatty liver disease 被引量:62
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作者 Feng Shen Rui-Dan Zheng +3 位作者 Xing-Qiang Sun Wen-Jin Ding Xiao-Ying Wang Jian-Gao Fan 《Hepatobiliary & Pancreatic Diseases International》 SCIE CAS CSCD 2017年第4期375-381,共7页
BACKGROUND: Gut microbiota plays a significant role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). This study aimed to assess the contribution of gut microbiota dysbiosis to the pathogenesis of NAFL... BACKGROUND: Gut microbiota plays a significant role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). This study aimed to assess the contribution of gut microbiota dysbiosis to the pathogenesis of NAFLD. METHODS: Forty-seven human feces samples (25 NAFLD patients and 22 healthy subjects) were collected and 16S rDNA amplicon sequencing was conducted on Hiseq 2000 platform. Discrepancy of species composition between controls and NAFLD group was defined by Metastats analysis under P value <0.01. RESULTS: NAFLD patients harbored lower gut microbiota diversity than healthy subjects did. In comparison to the control group, the Proteobacteria (13.50%) and Fusobacteria (2.76%) phyla were more abundant in NAFLD patients. Additionally, the Lachnospiraceae (21.90%), Enterobacteriaceae (12.02%), Erysipelotrichaceae (3.83%), and Streptococcaceae (1.39%) families, as well as the Escherichia_Shigella (10.84%), Lachnospiraceae_Incertae_Sedis (7.79%), and Blautia (4.95%) genera were enriched in the NAFLD group. However, there was a lower abundance of Prevotella in the NAFLD group than that in the control group (5.83% vs 27.56%, P<0.01). The phylum Bacteroidetes (44.63%) also tended to be more abundant in healthy subjects, and the families Prevotellaceae (28.66%) and Ruminococcaceae (26.44%) followed the same trend. Compared to those without non-alcoholic steatohepatitis (NASH), patients with NASH had higher abundance of genus Blautia (5.82% vs 2.25%; P=0.01) and the corresponding Lachnospiraceae family (24.33% vs 14.21%; P<0.01). Patients with significant fibrosis had a higher abundance of genus Escherichia_Shigella (12.53% vs 1.97%; P<0.01) and the corresponding Enterobacteriaceae family (13.92% vs 2.07%; P<0.01) compared to those with F0/F1 fibrosis. CONCLUSIONS: NAFLD patients and healthy subjects harbor varying gut microbiota. In contrast to the results of previous research on children, decreased levels of Prevotella might be detrimental for adults with NAFLD. The increased level of the genus Blautia, the fami 展开更多
关键词 gut microbiota fatty liver disease non-alcoholic steatohepatitis FIBROSIS
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Non-alcoholic fatty liver disease:An expanded review 被引量:63
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作者 Mark Benedict Xuchen Zhang 《World Journal of Hepatology》 CAS 2017年第16期715-732,共18页
Non-alcoholic fatty liver disease(NAFLD) encompasses the simple steatosis to more progressive steatosis with associated hepatitis, fibrosis, cirrhosis, and in some cases hepatocellular carcinoma. NAFLD is a growing ep... Non-alcoholic fatty liver disease(NAFLD) encompasses the simple steatosis to more progressive steatosis with associated hepatitis, fibrosis, cirrhosis, and in some cases hepatocellular carcinoma. NAFLD is a growing epidemic, not only in the United States, but worldwide in part due to obesity and insulin resistance leading to liver accumulation of triglycerides and free fatty acids. Numerous risk factors for the development of NAFLD have been espoused with most having some form of metabolic derangement or insulin resistance at the core of its pathophysiology. NAFLD patients are at increased risk of liver-related as well as cardiovascular mortality, and NAFLD is rapidly becoming the leading indication for liver transplantation. Liver biopsy remains the gold standard for definitive diagnosis, but the development of noninvasive advanced imaging, biochemical and genetic tests will no doubt provide future clinicians with a great deal of information and opportunity for enhanced understanding of the pathogenesis and targeted treatment. As it currently stands several medications/supplements are being used in the treatment of NAFLD; however, none seem to be the "magic bullet" in curtailing this growing problem yet. In this review we summarized the current knowledge of NAFLD epidemiology, risk factors, diagnosis, pathogenesis, pathologic changes, natural history, and treatment in order to aid in further understanding this disease and better managing NAFLD patients. 展开更多
关键词 non-alcoholic fatty liver disease Metabolic syndrome STEATOHEPATITIS Hepatocellular carcinoma STEATOSIS
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Risk of cardiovascular,cardiac and arrhythmic complications in patients with non-alcoholic fatty liver disease 被引量:58
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作者 Stefano Ballestri Amedeo Lonardo +3 位作者 Stefano Bonapace Christopher D Byrne Paola Loria Giovanni Targher 《World Journal of Gastroenterology》 SCIE CAS 2014年第7期1724-1745,共22页
Non-alcoholic fatty liver disease(NAFLD)has emerged as a public health problem of epidemic proportions worldwide.Accumulating clinical and epidemiological evidence indicates that NAFLD is not only associated with live... Non-alcoholic fatty liver disease(NAFLD)has emerged as a public health problem of epidemic proportions worldwide.Accumulating clinical and epidemiological evidence indicates that NAFLD is not only associated with liver-related morbidity and mortality but also with an increased risk of coronary heart disease(CHD),abnormalities of cardiac function and structure(e.g.,left ventricular dysfunction and hypertrophy,and heart failure),valvular heart disease(e.g.,aortic valve sclerosis)and arrhythmias(e.g.,atrial fibrillation).Experimental evidence suggests that NAFLD itself,especially in its more severe forms,exacerbates systemic/hepatic insulin resistance,causes atherogenic dyslipidemia,and releases a variety of pro-inflammatory,pro-coagulant and pro-fibrogenic mediators that may play important roles in the pathophysiology of cardiac and arrhythmic complications.Collectively,these findings suggest that patients with NAFLD may benefit from more intensive surveillance and early treatment interventions to decrease the risk for CHD and other cardiac/arrhythmic complications.The purpose of this clinical review is to summarize the rapidly expanding body of evidence that supports a strong association between NAFLD and cardiovascular,cardiac and arrhythmic complications,to briefly examine the putative biological mechanisms underlying this association,and to discuss some of the current treatment options that may influence both NAFLD and its related cardiac and arrhythmic complications. 展开更多
关键词 non-alcoholic fatty liver disease Cardiovascular disease Cardiac complications Coronary heart disease Myocardial dysfunction Valvular heart disease ARRHYTHMIAS Arrhythmic complications
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Gut-liver axis and probiotics: Their role in non-alcoholic fatty liver disease 被引量:57
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作者 Giulia Paolella Claudia Mandato +3 位作者 Luca Pierri Marco Poeta Martina Di Stasi Pietro Vajro 《World Journal of Gastroenterology》 SCIE CAS 2014年第42期15518-15531,共14页
The incidence of obesity and its related conditions, including non-alcoholic fatty liver disease (NAFLD), has dramatically increased in all age groups worldwide. Given the health consequences of these conditions, and ... The incidence of obesity and its related conditions, including non-alcoholic fatty liver disease (NAFLD), has dramatically increased in all age groups worldwide. Given the health consequences of these conditions, and the subsequent economic burden on healthcare systems, their prevention and treatment have become major priorities. Because standard dietary and lifestyle changes and pathogenically-oriented therapies (e.g., antioxidants, oral hypoglycemic agents, and lipid-lowering agents) often fail due to poor compliance and/or lack of efficacy, novel approaches directed toward other pathomechanisms are needed. Here we present several lines of evidence indicating that, by increasing energy extraction in some dysbiosis conditions or small intestinal bacterial overgrowth, specific gut microbiota and/or a &#x0201c;low bacterial richness&#x0201d; may play a role in obesity, metabolic syndrome, and fatty liver. Under conditions involving a damaged intestinal barrier (&#x0201c;leaky gut&#x0201d;), the gut-liver axis may enhance the natural interactions between intestinal bacteria/bacterial products and hepatic receptors (e.g., toll-like receptors), thus promoting the following cascade of events: oxidative stress, insulin-resistance, hepatic inflammation, and fibrosis. We also discuss the possible modulation of gut microbiota by probiotics, as attempted in NAFLD animal model studies and in several pilot pediatric and adult human studies. Globally, this approach appears to be a promising and innovative add-on therapeutic tool for NAFLD in the context of multi-target therapy. 展开更多
关键词 PROBIOTICS Gut-liver axis Intestinal microbiota Barrier function Small intestinal bacterial overgrowth Bacterial translocation non-alcoholic fatty liver disease
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Expression of p53,Bax and Bcl-2 proteins in hepatocytes in non-alcoholic fatty liver disease 被引量:48
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作者 Anatol Panasiuk Janusz Dzieciol +1 位作者 Bozena Panasiuk Danuta Prokopowicz 《World Journal of Gastroenterology》 SCIE CAS CSCD 2006年第38期6198-6202,共5页
AIM: To analyze the protein expression essential for apoptosis in liver steatosis. METHODS: The expression of proapoptotic proteins p53, Bax, and antiapoptotic Bcl-2 in hepatocytes with steatosis (SH) and without stea... AIM: To analyze the protein expression essential for apoptosis in liver steatosis. METHODS: The expression of proapoptotic proteins p53, Bax, and antiapoptotic Bcl-2 in hepatocytes with steatosis (SH) and without steatosis (NSH) was evaluated in 84 patients at various stages of non-alcoholic fatty liver disease (NAFLD). RESULTS: Immunohistochemical staining of liver tissue showed the activation of p53 protein in SH and NSH with increased liver steatosis, diminished Bcl-2 and slightly decreased Bax protein. Positive correlation was found between the stage of liver steatosis with p53 expression in SH (r = 0.54, P < 0.01) and NSH (r = 0.49, P < 0.01). The antiapoptotic protein Bcl-2 was diminished together with the advancement of liver steatosis, especially in non-steatosed hepatocytes (r =0.43, P < 001). CONCLUSION: Apoptosis is one of the most important mechanisms leading to hepatocyte elimination in NAFLD. The intensification of inflammation in NAFLD induces proapoptotic protein p53 with the inhibition of antiapoptotic Bcl-2. 展开更多
关键词 Apoptosis non-alcoholic liver disease P53 BCL-2 BAX IMMUNOHISTOCHEMISTRY
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Non-alcoholic fatty liver disease and obesity: Biochemical, metabolic and clinical presentations 被引量:53
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作者 Sandra Milic Davorka Lulic Davor Stimac 《World Journal of Gastroenterology》 SCIE CAS 2014年第28期9330-9337,共8页
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. Presentation of the disease ranges from simple steatosis to non-alcoholic steatohepatitis (NASH). NAFLD is a hepatic manifestati... Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. Presentation of the disease ranges from simple steatosis to non-alcoholic steatohepatitis (NASH). NAFLD is a hepatic manifestation of metabolic syndrome that includes central abdominal obesity along with other components. Up to 80% of patients with NAFLD are obese, defined as a body mass index (BMI) &#x0003e; 30 kg/m<sup>2</sup>. However, the distribution of fat tissue plays a greater role in insulin resistance than the BMI. The large amount of visceral adipose tissue (VAT) in morbidly obese (BMI &#x0003e; 40 kg/m<sup>2</sup>) individuals contributes to a high prevalence of NAFLD. Free fatty acids derived from VAT tissue, as well as from dietary sources and de novo lipogenesis, are released to the portal venous system. Excess free fatty acids and chronic low-grade inflammation from VAT are considered to be two of the most important factors contributing to liver injury progression in NAFLD. In addition, secretion of adipokines from VAT as well as lipid accumulation in the liver further promotes inflammation through nuclear factor kappa B signaling pathways, which are also activated by free fatty acids, and contribute to insulin resistance. Most NAFLD patients are asymptomatic on clinical presentation, even though some may present with fatigue, dyspepsia, dull pain in the liver and hepatosplenomegaly. Treatment for NAFLD and NASH involves weight reduction through lifestyle modifications, anti-obesity medication and bariatric surgery. This article reviews the available information on the biochemical and metabolic phenotypes associated with obesity and fatty liver disease. The relative contribution of visceral and liver fat to insulin resistance is discussed, and recommendations for clinical evaluation of affected individuals is provided. 展开更多
关键词 Fatty liver Insulin resistance Intra-abdominal fat METABOLISM non-alcoholic fatty liver disease OBESITY
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Treatment options for alcoholic and non-alcoholic fatty liver disease: A review 被引量:48
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作者 Sukhpreet Singh Natalia A Osna Kusum K Kharbanda 《World Journal of Gastroenterology》 SCIE CAS 2017年第36期6549-6570,共22页
Alcoholic liver disease(ALD)and non-alcoholic fatty liver disease(NAFLD)are serious health problems worldwide.These two diseases have similar pathological spectra,ranging from simple steatosis to hepatitis to cirrhosi... Alcoholic liver disease(ALD)and non-alcoholic fatty liver disease(NAFLD)are serious health problems worldwide.These two diseases have similar pathological spectra,ranging from simple steatosis to hepatitis to cirrhosis and hepatocellular carcinoma.Although most people with excessive alcohol or calorie intake display abnormal fat accumulation in the liver(simple steatosis),a small percentage develops progressive liver disease.Despite extensive research on understanding the pathophysiology of both these diseases there are still no targeted therapies available.The treatment for ALD remains as it was 50 years ago:abstinence,nutritional support and corticosteroids(or pentoxifylline as an alternative if steroids are contraindicated).As for NAFLD,the treatment modality is mainly directed toward weight loss and co-morbidity management.Therefore,new pathophysiology directed therapies are urgently needed.However,the involvement of several inter-related pathways in the pathogenesis of these diseases suggests that a single therapeutic agent is unlikely to be an effective treatment strategy.Hence,a combination therapy towards multiple targets would eventually be required.In this review,we delineate the treatment options in ALD and NAFLD,including various new targeted therapies that are currently under investigation.We hope that soon we will be having an effective multi-therapeutic regimen for each disease. 展开更多
关键词 alcoholic LIVER DISEASE non-alcoholic FATTY LIVER DISEASE Treatment OPTIONS GLUCOCORTICOIDS LIVER transplantation
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Non-alcoholic fatty liver disease: What the clinician needs to know 被引量:48
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作者 Mariana Verdelho Machado Helena Cortez-Pinto 《World Journal of Gastroenterology》 SCIE CAS 2014年第36期12956-12980,共25页
Non-alcoholic fatty liver disease(NAFLD) is the most frequent cause of liver disease in the Western world. Furthermore, it is increasing worldwide, paralleling the obesity pandemic. Though highly frequent, only about ... Non-alcoholic fatty liver disease(NAFLD) is the most frequent cause of liver disease in the Western world. Furthermore, it is increasing worldwide, paralleling the obesity pandemic. Though highly frequent, only about one fifth of affected subjects are at risk of developing the progressive form of the disease, non-alcoholic steatohepatitis with fibrosis. Even in the latter, liver disease is slowly progressive, though, since it is so prevalent, it is already the third cause of liver transplantation in the United States, and it is predicted to get to the top of the ranking in few years. Of relevance, fatty liver is also associated with increased overall mortality and particularly increased cardiovascular mortality. The literature and amount of published papers on NAFLD is increasing as fast as its prevalence, which makes it difficult to keep updated in this topic. This review aims to summarize the latest knowledge on NAFLD, in order to help clinicians understanding its pathogenesis and advances on diagnosis and treatment. 展开更多
关键词 non-alcoholic fatty liver disease Metabolic syndrome Insulin resistance Epidemiology PATHOGENESIS GENETICS Diagnosis Prognosis Management
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Current guidelines for the management of non-alcoholic fatty liver disease:A systematic review with comparative analysis 被引量:44
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作者 Simona Leoni Francesco Tovoli +3 位作者 Lucia Napoli Ilaria Serio Silvia Ferri Luigi Bolondi 《World Journal of Gastroenterology》 SCIE CAS 2018年第30期3361-3373,共13页
The current epidemic of non-alcoholic fatty liver disease(NAFLD) is reshaping the field of hepatology all around the world.The widespread diffusion of metabolic risk factors such as obesity,type2-diabetes mellitus,and... The current epidemic of non-alcoholic fatty liver disease(NAFLD) is reshaping the field of hepatology all around the world.The widespread diffusion of metabolic risk factors such as obesity,type2-diabetes mellitus,and dyslipidemia has led to a worldwide diffusion of NAFLD.In parallel to the increased availability of effective anti-viral agents,NAFLD is rapidly becoming the most common cause of chronic liver disease in Western Countries,and a similar trend is expected in Eastern Countries in the next years.This epidemic and its consequences have prompted experts from all over the word in identifying effective strategies for the diagnosis,management,and treatment of NAFLD.Different scientific societies from Europe,America,and Asia-Pacific regions have proposed guidelines based on the most recent evidence about NAFLD.These guidelines are consistent with the key elements in the management of NAFLD,but still,show significant difference about some critical points.We reviewed the current literature in English language to identify the most recent scientific guidelines about NAFLD with the aim to find and critically analyse the main differences.We distinguished guidelines from 5 different scientific societies whose reputation is worldwide recognised and who are representative of the clinical practice in different geographical regions.Differences were noted in: the definition of NAFLD,the opportunity of NAFLD screening in high-risk patients,the noninvasive test proposed for the diagnosis of NAFLD and the identification of NAFLD patients with advanced fibrosis,in the follow-up protocols and,finally,in the treatment strategy(especially in the proposed pharmacological management).These difference have been discussed in the light of the possible evolution of the scenario ofNAFLD in the next years. 展开更多
关键词 non-alcoholic fatty LIVER disease METFORMIN LIVER STEATOSIS LIVER biopsy non-invasive diagnosis PIOGLITAZONE Clinical GUIDELINES
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Adiponectin,a key adipokine in obesity related liver diseases 被引量:45
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作者 Christa Buechler Josef Wanninger Markus Neumeier 《World Journal of Gastroenterology》 SCIE CAS CSCD 2011年第23期2801-2811,共11页
Non-alcoholic fatty liver disease (NAFLD) comprising hepatic steatosis,non-alcoholic steatohepatitis (NASH),and progressive liver fibrosis is considered the most common liver disease in western countries.Fatty liver i... Non-alcoholic fatty liver disease (NAFLD) comprising hepatic steatosis,non-alcoholic steatohepatitis (NASH),and progressive liver fibrosis is considered the most common liver disease in western countries.Fatty liver is more prevalent in overweight than normal-weight people and liver fat positively correlates with hepatic insulin resistance.Hepatic steatosis is regarded as a benign stage of NAFLD but may progress to NASH in a subgroup of patients.Besides liver biopsy no diagnostic tools to identify patients with NASH are available,and no effective treatment has been established.Visceral obesity is a main risk factor for NAFLD and inappropriate storage of triglycerides in adipocytes and higher concentrations of free fatty acids may add to increased hepatic lipid storage,insulin resistance,and progressive liver damage.Most of the adipose tissue-derived proteins are elevated in obesity and may contribute to systemic inflammation and liver damage.Adiponectin is highly abundant in human serum but its levels are reduced in obesity and are even lower in patients with hepatic steatosis or NASH.Adiponectin antagonizes excess lipid storage in the liver and protects from inflammation and fibrosis.This review aims to give a short survey on NAFLD and the hepatoprotective effects of adiponectin. 展开更多
关键词 Hepatic steatosis non-alcoholic steatohepatitis ADIPONECTIN OBESITY Adipose tissue
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Non-alcoholic fatty liver disease: The diagnosis and management 被引量:45
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作者 Shehab M Abd El-Kader Eman M Salah El-Den Ashmawy 《World Journal of Hepatology》 CAS 2015年第6期846-858,共13页
Non-alcoholic fatty liver disease(NAFLD) is now the most frequent chronic liver disease that occurs across all age groups and is recognized to occur in 14%-30% of the general population, representing a serious and gro... Non-alcoholic fatty liver disease(NAFLD) is now the most frequent chronic liver disease that occurs across all age groups and is recognized to occur in 14%-30% of the general population, representing a serious and growing clinical problem due to the growing prevalence of obesity and overweight. Histologically, it resembles alcoholic liver injury but occurs in patients who deny significant alcohol consumption. NAFLD encompasses a spectrum of conditions, ranging from benign hepatocellular steatosisto inflammatory nonalcoholic steatohepatitis, fibrosis, and cirrhosis. The majority of hepatocellular lipids are stored as triglycerides, but other lipid metabolites, such as free fatty acids, cholesterol, and phospholipids, may also be present and play a role in disease progression. NAFLD is associated with obesity and insulin resistance and is considered the hepatic manifestation of the metabolic syndrome, a combination of medical conditions including type 2 diabetes mellitus, hypertension, hyperlipidemia, and visceral adiposity. Confirmation of the diagnosis of NAFLD can usually be achieved by imaging studies; however, staging the disease requires a liver biopsy. Current treatment relies on weight loss and exercise, although various insulin-sensitizing agents, antioxidants and medications appear promising. The aim of this review is to highlight the current information regarding epidemiology, diagnosis, and management of NAFLD as well as new information about pathogenesis, diagnosis and management of this disease. 展开更多
关键词 non-alcoholic fatty liver disease nonalcoholicsteatohepatitis Liver disease
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Non-alcoholic fatty liver disease in 2015 被引量:41
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作者 Monjur Ahmed 《World Journal of Hepatology》 CAS 2015年第11期1450-1459,共10页
There is worldwide epidemic of non-alcoholic fatty liver disease(NAFLD). NAFLD is a clinical entity related to metabolic syndrome. Majority of the patients are obese but the disease can affect non-obese individuals as... There is worldwide epidemic of non-alcoholic fatty liver disease(NAFLD). NAFLD is a clinical entity related to metabolic syndrome. Majority of the patients are obese but the disease can affect non-obese individuals as well. Metabolic factors and genetics play important roles in the pathogenesis of this disorder. The spectrum of disorders included in NAFLD are benign macrovesicular hepatic steatosis, non-alcoholic steatohepatitis, hepatic fibrosis, cirrhosis of liver and hepatocellular carcinoma. Although the disease remains asymptomatic most of the time, it can slowly progress to end stage liver disease. It will be the most common indication of liver transplantation in the future. It is diagnosed by abnormal liver chemistry, imaging studies and liver biopsy. As there are risks of potential complications during liver biopsy, many patients do not opt for liver biopsy. There are some noninvasive scoring systems to find out whether patients have advanced hepatic fibrosis. At the present time, there are limited treatment options which include lifestyle modification to loose weight, vitamin E and thioglitazones. Different therapeutic agents are being investigated for optimal management of this entity. There are some studies done on incretin based therapies in patients with NAFLD. Other potential agents will be silent information regulator protein Sirtuin and antifibrotic monoclonal antibody Simtuzumab against lysyl oxidase like molecule 2. But they are still in the investigational phase. 展开更多
关键词 Fatty LIVER Hepatic STEATOSIS non-alcoholicfatty LIVER disease non-alcoholic STEATOHEPATITIS
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Role of cytokines and chemokines in non-alcoholic fatty liver disease 被引量:44
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作者 Vincent Braunersreuther Giorgio Luciano Viviani +1 位作者 Franois Mach Fabrizio Montecucco 《World Journal of Gastroenterology》 SCIE CAS CSCD 2012年第8期727-735,共9页
Non-alcoholic fatty liver disease (NAFLD) includes a variety of histological conditions (ranging from liver steatosis and steatohepatitis, to fibrosis and hepatocarcinoma) that are characterized by an increased fat co... Non-alcoholic fatty liver disease (NAFLD) includes a variety of histological conditions (ranging from liver steatosis and steatohepatitis, to fibrosis and hepatocarcinoma) that are characterized by an increased fat content within the liver. The accumulation/deposition of fat within the liver is essential for diagnosis of NAFLD and might be associated with alterations in the hepatic and systemic inflammatory state. Although it is still unclear if each histological entity represents a different disease or rather steps of the same disease, inflammatory processes in NAFLD might influence its pathophysiology and prognosis. In particular, non-alcoholic steatohepatitis (the most inflamed condition in NAFLDs, which more frequently evolves towards chronic and serious liver diseases) is characterized by a marked activation of inflammatory cells and the upregulation of several soluble inflammatory mediators. Among several mediators, cytokines and chemokines might play a pivotal active role in NAFLD and are considered as potential therapeutic targets. In this review, we will update evidence from both basic research and clinical studies on the potential role of cytokines and chemokines in the pathophysiology of NAFLD. 展开更多
关键词 INFLAMMATION non-alcoholic fatty liver disease CYTOKINE CHEMOKINE
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Metabolic syndrome and non-alcoholic fatty liver disease:Asian definitions and Asian studies 被引量:42
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作者 Fan, Jian-Gao Peng, Yong-De 《Hepatobiliary & Pancreatic Diseases International》 SCIE CAS 2007年第6期572-578,共7页
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), as conventionally recognized, is a metabolic disorder largely confined to residents of affluent industrialized Western countries. However, obesity and insulin res... BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), as conventionally recognized, is a metabolic disorder largely confined to residents of affluent industrialized Western countries. However, obesity and insulin resistance are not restricted to the West, as witnessed by their increasingly universal distribution. In particular, there has been an upsurge in metabolic syndrome in the Asia-Pacific region, although there are critical differences in the extent of adiposity between Eastern and Western populations. DATA SOURCES: An English-language literature search using PubMed (1999-2007) on obesity, metabolic syndrome and NAFLD, focusing on Asian definitions and Asian studies. RESULTS: NAFLD appears to be of long-standing insulin resistance and likely represents the hepatic manifestation of the metabolic syndrome. With insulin resistance as a common factor, the disease is associated with atherosclerosis and cardiovascular risk. All features of the metabolic syndrome and related events are assessed for practical management of NAFLD, although the criteria for the diagnosis of obesity and central obesity differ across racial groups. CONCLUSIONS: The increasing prevalence of obesity, coupled with diabetes, dyslipidemia, hypertension and ultimately metabolic syndrome, puts a very large population at risk of developing NAFLD in the coming decades. The simultaneous identification and appropriate treatment of the components of metabolic syndrome are crucial to reduce hepatic as well as cardiovascular morbidity and mortality. 展开更多
关键词 metabolic syndrome non-alcoholic fatty liver disease OBESITY diabetes mellitus insulin resistance
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Prevalence of and risk factors for non-alcoholic fatty liver disease in a Chinese population: An 8-year follow-up study 被引量:42
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作者 Zhen-Ya Lu Zhou Shao +2 位作者 Ya-Li Li Muhuyati Wulasihan Xin-Hua Chen 《World Journal of Gastroenterology》 SCIE CAS 2016年第13期3663-3669,共7页
AIM: To investigate the prevalence of and risk factors for non-alcoholic fatty liver disease(NAFLD) in a Chinese population.METHODS: A total of 1948 adults from China was followed for 8 years. A cross-sectional study ... AIM: To investigate the prevalence of and risk factors for non-alcoholic fatty liver disease(NAFLD) in a Chinese population.METHODS: A total of 1948 adults from China was followed for 8 years. A cross-sectional study was performed to investigate the prevalence of NAFLD at baseline, and then the participants were followed for 8 years to investigate risk factors for the development of NAFLD.RESULTS: A total of 1948 participants were enrolled at baseline, of whom 691 were diagnosed with NAFLD. During the 8-year follow-up, 337 baseline NAFLD-free participants developed NAFLD. They had a greaterincrease in body mass index(BMI), serum uric acid, fasting plasma glucose, very low-density lipoprotein cholesterol and a considerable decrease in high-density lipoprotein cholesterol. 123 participants who had NAFLD at baseline lost NAFLD during the 8-year follow-up period. They had a greater decrease in BMI, fasting plasma glucose, triglycerides, total cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase, and γ-glutamyl transpeptidase.CONCLUSION: NAFLD is prevalent in Chinese population with a rapidly increasing tendency. It can be reversed when patients lose their weight, control their hyperlipidemia and hyperglycemia, and reduce the liver enzyme levels. 展开更多
关键词 non-alcoholic FATTY LIVER disease FOLLOW-UP PREVALENCE Risk factors
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肝癖(非酒精性脂肪性肝炎)诊疗方案 被引量:40
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作者 童光东 邢宇锋 +2 位作者 周晓玲 池晓玲 韩志毅 《中国肝脏病杂志(电子版)》 CAS 2021年第1期1-9,共9页
随着生活水平的提高,中国脂肪性肝病(简称脂肪肝)的发病率逐年提高,已成为我国第一大肝病。脂肪肝的危害正在逐步被医学界重视,但目前尚缺乏有效的药物治疗,中医药在脂肪肝方面的优势已得到广大医生和患者的认可。为进一步提高脂肪肝的... 随着生活水平的提高,中国脂肪性肝病(简称脂肪肝)的发病率逐年提高,已成为我国第一大肝病。脂肪肝的危害正在逐步被医学界重视,但目前尚缺乏有效的药物治疗,中医药在脂肪肝方面的优势已得到广大医生和患者的认可。为进一步提高脂肪肝的中医药疗效,深圳市中医院肝病科依托国家中医药管理局华南区中医肝病诊疗中心联盟理事长单位,牵头联合广东省、广西壮族自治区和海南省肝病专家,以国家中医药管理局发布的《肝癖(脂肪性肝病)诊疗方案》为蓝本,结合脂肪肝的研究进展,更新、修订形成了《肝癖(非酒精性脂肪性肝炎)诊疗方案》,为华南区肝癖的中医预防、辨证治疗提供依据。 展开更多
关键词 肝癖 脂肪性肝炎 非酒精性 中医诊疗方案 临床路径
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