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Non-alcoholic fatty liver disease: an overview 总被引:12,自引:0,他引:12
Non-alcoholic fatty liver disease (NAFL) includes a spectrum of clinicopathological conditions with increasing prevalence in the developed world. Although steatosis alone seems to have a benign course, those patients with the diagnosis of non-alcoholic steatohepatitis (NASH) can have a progressive course. Additionally, there is now evolving, indirect evidence that some of the patients with cryptogenic cirrhosis may be the result of 'burned-out' NASH. Although NAFL and NASH are associated with insulin-resistance syndrome, some patients with NAFL may have no obvious risk factors. Despite preliminary data from a number of pilot studies, no established therapies can be offered to patients with NASH. Over the next few years, a number of exciting research projects dealing with the epidemiology as well as the pathogenesis of NAFL are expected to be completed. It is anticipated that, through a better understanding of NAFL, more effective treatment protocols can be developed targeting only those patients with NASH that are at the highest risk for progression to cirrhosis and liver failure. 相似文献
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Tarantino G Saldalamacchia G Conca P Arena A 《Journal of gastroenterology and hepatology》2007,22(3):293-303
Non-alcoholic fatty liver disease has been associated with metabolic disorders, including central obesity, dyslipidemia, hypertension and hyperglycemia. Metabolic syndrome, obesity, and insulin resistance are major risk factors in the pathogenesis of non-alcoholic fatty liver disease. Non-alcoholic fatty liver disease refers to a wide spectrum of liver damage, ranging from simple steatosis to non-alcoholic steatohepatitis, advanced fibrosis and cirrhosis. 相似文献
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Sara Heebøll Martin Kreuzfeldt Stephen Hamilton-Dutoit Marianne Kjær Poulsen Hans Stødkilde-Jørgensen Holger Jon Møller 《Scandinavian journal of gastroenterology》2016,51(4):456-464
Objective “The obesity epidemic” has led to an increase in obesity-related conditions including non-alcoholic fatty liver disease (NAFLD), for which effective treatments are in demand. The polyphenol resveratrol prevents the development of experimental NAFLD through modulation of cellular pathways involved in calorie restriction. We aimed to test the hypothesis that resveratrol alleviates NAFLD in a randomised, clinical trial. Materials and methods A total of 28 overweight patients with transaminasemia and histological NAFLD were randomised 1:1 to placebo or resveratrol 1.5 g daily for 6 months. Twenty-six participants completed the trial and underwent repeated clinical investigation, blood work, MR spectroscopy; and 19 participants agreed to a repeat liver biopsy. Results Resveratrol treatment was generally not superior to placebo in improving plasma markers of liver injury (primary outcome: alanine transaminase, p?=?0.51). Resveratrol-treated patients showed a 3.8% decrease in liver lipid content (p?=?0.03), with no difference between the two treatment arms (p?=?0.38) and no improvement of histological features. Resveratrol treatment was not associated with improvements in insulin sensitivity or markers of the metabolic syndrome, except for a transient decrease in systolic BP. Microarray analysis and qRT-PCR revealed no major changes in expression profile. Also, we report a serious adverse event in a patient who developed fever and bicytopenia. Conclusions In this placebo-controlled, high-dose and long-term study, resveratrol treatment had no consistent therapeutic effect in alleviating clinical or histological NAFLD, though there may be a small ameliorating effect on liver function tests and liver fat accumulation. 相似文献
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Masato Yoneda Kikuko Hotta Yuichi Nozaki Hiroki Endo Wataru Tomeno Seitaro Watanabe Kunihiro Hosono Hironori Mawatari Hiroshi Iida Koji Fujita Hirokazu Takahashi Hiroyuki Kirikoshi Noritoshi Kobayashi Masahiko Inamori Kensuke Kubota Takeshi Shimamura Satoru Saito Shiro Maeyama Koichiro Wada Atsushi Nakajima 《Hepatology research》2009,39(10):963-971
Aim: Genetic factors as well as environmental factors play an important role in the development of non-alcoholic fatty liver disease (NAFLD). Recently, inducible nitric oxide synthase (iNOS) was significantly higher in the severest form of non-alcoholic steatohepatitis (NASH), and nitric oxide (NO) has been determined to play an important role in the process of fibrosis in NASH. In this study, we investigated iNOS gene polymorphisms for associations with NAFLD.
Methods: A total of 115 NAFLD patients, consisting of 65 patients with NASH and 50 patients with simple steatosis, in whom a positive diagnosis had been made by liver biopsy, and 435 healthy control subjects, were recruited into this study.
Results: We investigated 10 single nucleotide polymorphisms (SNP) of the iNOS gene, one of which, rs1060822, had the lowest P -value in the allele frequency model ( P = 0.00078) with an odds ratio (95% confidence interval) of 0.49 (0.32–0.75). Four SNP, rs2297510, rs2297511, rs2797512 and rs1060822, were significantly associated with NAFLD, even when the most conservative Bonferroni's correction was applied. Linkage disequilibrium analysis revealed that SNP rs1060822 and three other SNP, rs2297510, rs2297511 and rs2797512, were in the same block. We also investigated associations between rs1060822 genotypes and the fibrosis index, and the results of the analysis revealed an additive increase in the fibrosis index and intrahepatic iNOS mRNA expression in the patients with the T allele of rs1060822.
Conclusion: This is the first study to identify genetic variations in iNOS that may influence the risk of NAFLD and liver fibrosis in NAFLD. 相似文献
Methods: A total of 115 NAFLD patients, consisting of 65 patients with NASH and 50 patients with simple steatosis, in whom a positive diagnosis had been made by liver biopsy, and 435 healthy control subjects, were recruited into this study.
Results: We investigated 10 single nucleotide polymorphisms (SNP) of the iNOS gene, one of which, rs1060822, had the lowest P -value in the allele frequency model ( P = 0.00078) with an odds ratio (95% confidence interval) of 0.49 (0.32–0.75). Four SNP, rs2297510, rs2297511, rs2797512 and rs1060822, were significantly associated with NAFLD, even when the most conservative Bonferroni's correction was applied. Linkage disequilibrium analysis revealed that SNP rs1060822 and three other SNP, rs2297510, rs2297511 and rs2797512, were in the same block. We also investigated associations between rs1060822 genotypes and the fibrosis index, and the results of the analysis revealed an additive increase in the fibrosis index and intrahepatic iNOS mRNA expression in the patients with the T allele of rs1060822.
Conclusion: This is the first study to identify genetic variations in iNOS that may influence the risk of NAFLD and liver fibrosis in NAFLD. 相似文献
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Fiorella Piemonte Stefania Petrini Laura Maria Gaeta Giulia Tozzi Enrico Bertini Rita Devito Renata Boldrini Matilde Marcellini Enzo Ciacco Valerio Nobili 《Journal of gastroenterology and hepatology》2008,23(8PT2):e457-e464
Background and Aim: Oxidative stress is an important pathophysiological mechanism in non-alcoholic steatohepatitis, where hepatocyte apoptosis is significantly increased correlating with disease severity. Protein glutathionylation occurs as a response to oxidative stress, where an increased concentration of oxidized glutathione modifies post-translational proteins by thiol disulfide exchange. In this study, we analyzed the protein glutathionylation in non-alcoholic fatty liver disease (NAFLD) and evaluated a potential association between glutathionylation, fibrosis, and vitamin E treatment.
Methods: Protein glutathionylation was studied in the livers of 36 children (mean age 12.5 years, range 4–16 years) subdivided into three groups according to their NAFLD activity score (NAS) by Western blot analysis and immunohistochemistry, using a specific monoclonal antibody. In addition, we identified the hepatocyte ultrastructures involved in glutathionylation by immunogold electron microscopy.
Results: Our findings showed that protein glutathionylation increases in the livers of patients with NAFLD and it is correlated with steatohepatitis and liver fibrosis. Its increase appears mainly in nuclei and cytosol of hepatocytes, and it is reversed by antioxidant therapy with reduced fibrosis.
Conclusion: Protein glutathionylation significantly increases in livers with NAFLD, strongly suggesting that oxidative injury plays a crucial role in this disease. Furthermore, the marked increase of protein glutathionylation, in correlation with collagen VI immunoreactivity, suggests a link between the redox status of hepatic protein thiols and fibrosis. 相似文献
Methods: Protein glutathionylation was studied in the livers of 36 children (mean age 12.5 years, range 4–16 years) subdivided into three groups according to their NAFLD activity score (NAS) by Western blot analysis and immunohistochemistry, using a specific monoclonal antibody. In addition, we identified the hepatocyte ultrastructures involved in glutathionylation by immunogold electron microscopy.
Results: Our findings showed that protein glutathionylation increases in the livers of patients with NAFLD and it is correlated with steatohepatitis and liver fibrosis. Its increase appears mainly in nuclei and cytosol of hepatocytes, and it is reversed by antioxidant therapy with reduced fibrosis.
Conclusion: Protein glutathionylation significantly increases in livers with NAFLD, strongly suggesting that oxidative injury plays a crucial role in this disease. Furthermore, the marked increase of protein glutathionylation, in correlation with collagen VI immunoreactivity, suggests a link between the redox status of hepatic protein thiols and fibrosis. 相似文献
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《Expert Review of Gastroenterology & Hepatology》2013,7(4):343-349
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease etiology worldwide. It encompasses a spectrum ranging from simple steatosis to non-alcoholic steatohepatitis. Although the physiopathology of NAFLD is partly known. Insulin-resistance plays a central role in the development and progression of NAFLD. Several studies have indicated that metformin, as an insulin sensitizer, effectively improves NAFLD and its related metabolic status. Metformin was effective in reducing enzyme levels in the short period, but very limited and controversial information are available on liver histology. Larger randomized controlled trials of sufficient duration using clearly defined histological endpoints are needed to fully assess the efficacy of this drug in modifying the natural history of NAFLD. 相似文献
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成人非酒精性脂肪肝与代谢综合征关系的研究 总被引:7,自引:0,他引:7
目的探讨非酒精性脂肪肝(NAFLD)和代谢综合征(MS)的关系。方法对2006年10~12月长沙市某企业3744例20岁以上职工进行问卷调查、体格检查、空腹血糖、血脂、丙氨酸转氨酶、血尿酸检测以及肝脏B超检查。结果(1)NAFLD患病率23.5%,MS患病率22.8%,两病的共患病率12.6%。(2)MS、中心性肥胖、血压升高、空腹血糖升高、高三酰甘油、低高密度脂蛋白胆固醇各组NAFLD患病风险分别是对照组的13.4~22.2倍。(3)以NAFLD取代MS5个组分中的任何一个后,与原诊断定义相比有较高一致性(Kappa值0.53~0.89,P<0.01)。(4)采用多因素Logistic回归分析,调整了性别、年龄和多项代谢成分的影响后,NAFLD与MS独立相关(OR2.342,95%CI:1.825~3.007;P<0.01)。结论该人群中1/5以上患有NAFLD和MS,且NAFLD与MS密切相关;NAFLD可纳入MS的组成成分。 相似文献
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非酒精性脂肪肝与胰岛素抵抗 总被引:1,自引:0,他引:1
目的探讨非酒精性脂肪性肝病(NAFLD)与胰岛素抵抗(IR)的关系。方法NAFLD组52例,非NAFLD组50例,比较两组间BMI、WHR、TC、TG、CRP、HDL-C、LDL-C、ALT、Cr、FBG、FINS和HOMA-IR的差异,并进行Logistic回归分析。结果NAFLD组与非NAFLD组在BMI(26.7±2.3与22.4±2.5,P〈0.01)、WHR(0.94±0.06与0.83±0.05,P〈0.01)、TG(2.4±0.6与1.8±0.6,P〈0.01)、ALT(37.3±8.3与28.1±7.2,P〈0.05)、FBG(6.2±1.4与5.2±0.7,P〈0.01)、FINS(23.6±13.6与8.6±3.5,P〈0.01)、HOMA-IR(6.7±4.7与2.0±1.6,P〈0.01)的差异有统计学意义,Logistic回归分析显示BMI(P〈0.01)、WHR(P〈0.01)、TG(P〈0.01)、ALT(P〈0.05)、HOMA-IR(P〈0.01)是NAFLD的独立影响因素。结论BMI、WHR、TG、ALT、HOMA-IR是NAFLD的独立影响因素。 相似文献
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目的 探讨非酒精性脂肪肝(NAFLD)与生长激素(GH)的关系。方法入选NAFLD组38例,非NAFLD组42例.测定GH、腰围(Wc)、空腹血糖(FPG)、空腹胰岛素(Fins)、总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL—C)、低密度脂蛋白胆固醇(LDL—C)、高敏c反应蛋白(hs—CRP),谷氨酸氨基转移酶(AIJrr)、γ-谷氨酰转肽酶(GGT)水平,计算体质量指数(BMI)、胰岛素抵抗指数(HOMA—IR)。结果NAFLD组GH、HDL—C水平显著低于非NAFLD组(P〈0.05);NAFLD组BMI、WC、FPG、Fins、HOMA—IR、TG、hsCRP、AIJT、GGT水平显著高于非NAFLD组(P〈0.05)。GH、HDL—C与NAFLD呈负相关,WC、BMI、FPG、Fins、HOMA—IR、TG、hsCRP、ALT、GGT与NAFLD呈正相关。结论GH与NAFLD密切相关,低水平CH可能是NAFLD危险因素,与肥胖、胰岛素抵抗、血脂紊乱等共同参与了NAFLD的发生与发展。 相似文献
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Chitturi S Farrell GC Hashimoto E Saibara T Lau GK Sollano JD;Asia-Pacific Working Party on NAFLD 《Journal of gastroenterology and hepatology》2007,22(6):778-787
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in Western industrialized countries, affecting 20-40% of the general population. Large population-based surveys in China, Japan, and Korea indicate that the prevalence of NAFLD is now 12% to 24% in population subgroups, depending on age, gender, ethnicity, and location (urban versus rural). There is strong evidence that the prevalence of NAFLD has increased recently in parallel with regional trends in obesity, type 2 diabetes, and metabolic syndrome; and that further increases are likely. The relationship between NAFLD, central obesity, diabetes, and metabolic syndrome is clearly evident in retrospective and prospective Asian studies, but the strength of association with these metabolic risk factors is only appreciated when regional definitions of anthropometry are used. Pathological definition of NAFLD, particularly its activity and the extent of liver fibrosis, requires histological examination, but liver biopsy is often not appropriate in this disorder for logistic reasons. An alternative set of operational definitions is proposed here. Clinicians need guidelines as how best to diagnose and manage NAFLD and its associated metabolic disorders in countries with scant healthcare resources. The Asia-Pacific Working Party (APWP) for NAFLD was convened to collate evidence and deliberate these issues. Draft proposals were presented and discussed at Asia-Pacific Digestive Week at Cebu, Philippines, in late November 2006, and are published separately in this issue of the Journal as an Executive Summary. The present document reviews the reasoning and evidence behind the APWP-NAFLD proposals for definition, assessment, and management of NAFLD in the Asia-Pacific region. 相似文献
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随着非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)流行率的上升以及对其危害的全面认识,其诊断和治疗发展迅速。本文介绍了新的NAFLD病理学评分系统和病理学检查指征;在无创性诊断方面概述了肝脏脂肪变性、肝脏炎症和纤维化无创性诊断的现有方法及最新进展,以及疾病进展风险因素;在治疗方面,描述了饮食控制要点,并介绍了抗阻运动联合有氧运动和避免静坐的三联运动方式;在药物治疗方面,介绍了维生素E和吡格列酮2个重点药物的优缺点。最后,简述了以疾病分级为基础的检测和治疗策略。 相似文献
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Non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH): diagnosis and clinical course 总被引:1,自引:0,他引:1
Non-alcoholic fatty liver disease (NAFLD) is a frequent syndrome encompassing fatty liver alone and steatohepatitis (NASH). Often asymptomatic, the suspicion arises because of abnormal aminotransferases or a bright liver on abdominal ultrasound. It should be suspected during evaluation of associated conditions as obesity, diabetes or dyslipidaemia. The diagnostic evaluation must exclude other potential causes of liver disease and may include a liver biopsy, the only method able to confirm features of necroinflammation and fibrosis that define NASH and its prognostic implications. Indeed, the presence of necroinflammation has been associated with a significant risk of progression to cirrhosis and eventually hepatocellular carcinoma. Age >45 years, obesity and diabetes have also been associated with an increased risk of liver fibrosis and progression to cirrhosis. Given the high prevalence of NAFLD, general measures of life-style changes, focusing on exercise, diet, and total alcohol abstinence, should be implemented before a liver biopsy is considered. 相似文献