酒精性与非酒精性脂肪性肝病

脂肪性肝病(FLD)根据有无过量饮酒史,分为酒精性肝病(ALD)和非酒精性脂肪性肝病(NAFLD)两大类。两者享有FLD的许多共性特征,但又各有其独特之处。 1.酒精性与非酒精性FLD的异同:NAFLD的肝组织学改变与ALD相似,包括单纯性脂肪肝、脂肪性肝炎及肝硬化。我国及日本学者认为ALD还应包括轻症ALD、酒精性重型肝炎及酒精性肝纤维化,事实上NAFLD均有其相对应的临床病理类     

非酒精性脂肪性肝病与乙型肝炎病毒既往感染者肝癌发生关系的研究

目的:乙型肝炎表面抗原（HBsAg）清除并不能消除乙型肝炎病毒（HBV）感染患者的肝细胞癌（HCC）风险,本研究旨在探讨非酒精性脂肪性肝病（NAFLD）在HBV既往感染者（HBsAg阴性、抗-HBc阳性）HCC发生中的作用。方法:本研究是回顾性调查研究,纳入2015年至2017年在南方医院住院并首次诊断为HCC的患者共...     

非酒精性脂肪性肝病动物模型研究进展

近年来,随着生活水平和饮食结构的改变,非酒精性脂肪性肝病的发病率呈逐年上升的趋势,在一般人群中的发病率高达29.81%。越来越多的流行病学证据表明,非酒精性脂肪性肝病已成为日益增长的肝硬化和肝癌的原因之一。但其病因和发病机制复杂,至今尚未完全阐明。构建非酒精性脂肪性肝病合适的动物模型进行临床前研究,对于阐明其发病机制至...     

非酒精性脂肪性肝病与肝细胞癌发生

肝细胞癌的发病率在全球逐年升高。绝大多数肝细胞癌与肝炎病毒感染有关,然而非酒精性脂肪性肝病也是引起肝细胞癌的重要原因之一。近年来,随着饮食习惯及生活方式的改变,非酒精性脂肪性肝病发病率持续升高,其与肝细胞癌发生的关系也得到了更多的关注。本文主要从非酒精性脂肪性肝病相关肝细胞癌的发病进程、危险因素及发病机制等方面做一介绍。     

非酒精性脂肪性肝病相关肝细胞癌的研究进展

非酒精性脂肪性肝病相关肝细胞癌发病率在世界范围内呈增长趋势,然而其发病机制仍不明确。结合近年文献,总结脂肪组织炎症、氧化应激、肠道菌群及胰岛素抵抗在非酒精性脂肪性肝病相关肝细胞癌发病过程中的作用,并针对以上机制的防治进展进行综述,为其治疗提供新思路。     

非酒精性脂肪性肝病相关肝细胞癌发病机制研究进展

非酒精性脂肪性肝病（NAFLD）是目前临床上最常见的慢性肝病之一,NAFLD相关肝细胞癌（NAFLD-HCC）的发病率也逐年上升。众多因素参与了NAFLD-HCC的发生发展,但其具体的发病机制还不清楚。本文重点介绍近年有关其发病机制的研究进展。     

非酒精性脂肪性肝病病证结合动物模型的研究进展

随着肥胖和糖尿病的发病率增加,非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)现已成为我国常见的慢性肝病之一,严重危害人民健康.目前中医应用辨证论治方法治疗NAFLD,取得了一定成绩,但NAFLD动物实验研究采用的模型,没有将中医"证"的因素考虑其中,这样的实验研究或将在某种程度上,影响了中医药治疗该病的疗效及其机制的深入探讨.因此,本文对NAFLD病证结合模型的研究作一深入探讨.     

解读非酒精性脂肪性肝病诊治指南

随着肥胖与糖尿病患者的日趋增多,脂肪性肝病(FLD)目前已成为全球性的重要肝病。临床上FLD分为酒精性肝病(ALD)与非酒精性脂肪性肝病(NAFLD);研究表明,NAFLD与肥胖、代谢综合征、2型糖尿病和心血管疾病密切相关。2006年和2010年中华医学会相继制定了中国NAFLD诊疗指南,较全面和广泛地反映了目前NAFLD的临床诊疗现状,与国际上颁布的一些诊治指南相比存在差异。本文就NAFLD诊治指南及相关问题进行解读。     

非酒精性脂肪性肝病相关性肝细胞癌治疗的研究进展

肝细胞癌(HCC)发病率高,乙型肝炎病毒(HBV)和丙型肝炎病毒(HCV)感染是HCC的主要病因.近年来,肥胖、2型糖尿病等代谢疾病的流行加速了非酒精性脂肪性肝病(NAFLD)的发生,导致NAFLD相关性HCC(NAFLD-HCC)的发生也逐年递增.但NAFLD-HCC与病毒相关性HCC是否有相似的发病机制、预防、监测...     

Screening and interventions to prevent nonalcoholic fatty liver disease/nonalcoholic steatohepatitis-associated hepatocellular carcinoma

Liver cancer is the sixth most commonly diagnosed cancer worldwide, with hepatocellular carcinoma (HCC) comprising most cases. Besides hepatitis B and C viral infections, heavy alcohol use, and nonalcoholic steatohepatitis (NASH)-associated advanced fibrosis/cirrhosis, several other risk factors for HCC have been identified (i.e. old age, obesity, insulin resistance, type 2 diabetes). These might in fact partially explain the occurrence of HCC in non-cirrhotic patients without viral infection. HCC surveillance through effective screening programs is still an unmet need for many nonalcoholic fatty liver disease (NAFLD) patients, and identification of pre-cirrhotic individuals who progress to HCC represents a substantial challenge in clinical practice at the moment. Patients with NASH-cirrhosis should undergo systematic HCC surveillance, while this might be considered in patients with advanced fibrosis based on individual risk assessment. In this context, interventions that potentially prevent NAFLD/ NASH-associated HCC are needed. This paper provided an overview of evidence related to lifestyle changes (i.e. weight loss, physical exercise, adherence to healthy dietary patterns, intake of certain dietary components, etc.) and pharmacological interventions that might play a protective role by targeting the underlying causative factors and pathogenetic mechanisms. However, well-designed prospective studies specifically dedicated to NAFLD/NASH patients are still needed to clarify the relationship with HCC risk.     

非酒精性脂肪性肝病与原发性肝癌相关性探讨

目的探讨非酒精性脂肪性肝病（NAFLD）伴发原发性肝癌（HCC）的发病率、临床特征和危险因素。方法采用回顾性分析的方法,选取该院住院确诊的1 092例HCC患者,参照2006-02中华医学会肝脏病分会脂肪肝和酒精性肝病学组《非酒精性脂肪性肝病诊疗指南》中关于NAFLD的临床诊断标准,从HCC患者中遴选出符合NAFLD诊断标准的72例患者,分析NAFLD相关HCC的发病率、临床表现及生化指标、影像学特征、生存率及影响预后的危险因素。结果 NAFLD伴发HCC患者共72例,占HCC患者的6.6%,年龄（60.52±10.21）岁,伴有2型糖尿病（T2DM）者35例,占48.6%（35/72）,体重指数（BMI）≥26 kg/m2者28例,占38.9%（28/72）,伴有高血压病者34例,占47.2%（34/72）。主要临床表现无明显特征性。其生存情况：随访NAFLD伴发HCC病例72例,死亡53例,1、2、3年生存率分别为68.47%、40.26%、30.52%。单因素分析BMI、T2DM、高血压病、谷丙转氨酶（ALT）、总胆红素（TBIL）、直接胆红素（DBIL）、谷氨酰转移酶（GGT）、胆碱酯酶（CHE）对NAFLD伴发HCC生存率比较差异有统计学意义（P〈0.05）,可能是影响预后的危险因素。多因素分析显示BMI、T2DM是影响预后的独立危险因素。结论 NAFLD是HCC发生的原因之一,肥胖、T2DM是影响NAFLD伴发HCC预后的独立危险因素。     

NAFLD与肝细胞癌的相关性研究进展*

非酒精性脂肪性肝病（NAFLD）已成为世界范围内最常见的慢性肝脏疾病,被认为是代谢综合征在肝脏的表现,其疾病谱从轻微肝细胞脂肪变性到非酒精性脂肪性肝炎（NASH）,进一步可发展为肝硬化或肝细胞癌（HCC）。随着肥胖及胰岛素抵抗问题的日益严重,NAFLD、NASH及其相关肝硬化、肝癌患者也日益增多。近年来研究表明,NASH可不经肝硬化阶段直接发展为HCC,具体机制尚不明确。     

Nonalcoholic fatty liver disease,metabolic risk factors,and hepatocellular carcinoma: An open question

Non-alcoholic liver disease(NAFLD) defines liver abnormalities ranging from simple steatosis to nonalcoholic steatohepatitis with or without cirrhosis development, occurring in the absence of significant alcohol consumption, use of teratogenic medication, or hereditary disorders. The association between NAFLD and metabolic syndrome is well documented and widely recognized. Obesity, type 2 diabetes mellitus(T2DM), and dyslipidemia are the most common metabolic risk factors associated with NAFLD. Among the components of metabolic syndrome, current evidence strongly indicates obesity and diabetes as hepatocellular carcinoma(HCC) risk factors. There is also growing evidence that suggests an increased risk of HCC in NAFLD patients, even surpassing other etiologies in some high-income countries. Epidemiologic data demonstrate a parallel rise in prevalence of obesity, diabetes, NAFLD, and HCC. As obesity and its related diseases have steadily afflicted larger populations, HCC incidence is expected to increase in the future. Pathophysiologic mechanisms that underlie NAFLD development and subsequent progression to nonalcoholic steatohepatitis and cirrhosis(insulin resistance and hyperinsulinemia, oxidative stress, hepatic stellate cell activation, cytokine/adipocytokine signaling pathways, and genetic and environmental factors) appear to play a significant role in the development of NAFLD-related HCC. However, a comprehensive view of molecular mechanisms linking obesity, T2 DM, and NAFLD-related HCC, as well as the exact sequence of molecular events, is still not understood in its entirety. Good-quality data are still necessary, and efforts should continue towards better understanding the underlying carcinogenic mechanisms of NAFLD-related HCC. In this paper, we aimed to centralize the most important links supporting these relationships, focusing on obesity, T2 DM, and NAFLD-related HCC, as well as point out the major gaps in knowledge regarding the underlying molecular mechanisms behind them.     

Hepatocellular carcinoma in nonalcoholic fatty liver disease: A growing challenge

Nonalcoholic fatty liver disease(NAFLD) is the most common cause of liver disease worldwide, and its prevalence increases continuously. As it predisposes to hepatocellular carcinoma both in the presence and in the absence of cirrhosis, it is not surprising that the incidence of NAFLD-related hepatocellular carcinoma would also rise. Some of the mechanisms involved in hepatocarcinogenesis are particular to individuals with fatty liver, and they help explain why liver cancer develops even in patients without cirrhosis. Genetic and immune-mediated mechanisms seem to play an important role in the development of hepatocellular carcinoma in this population. Currently, it is consensual that patients with NAFLD-related cirrhosis should be surveilled with ultrasonography every 6 mo (with or without alpha-fetoprotein), but it is known that they are less likely to follow this recommendation than individuals with other kinds of liver disease. Moreover, the performance of the methods of surveillance are lower in NAFLD than they are in other liver diseases. Furthermore, it is not clear which subgroups of patients without cirrhosis should undergo surveillance. Understanding the mechanisms of hepatocarcinogenesis in NAFLD could hopefully lead to the identification of biomarkers to be used in the surveillance for liver cancer in these individuals. By improving surveillance, tumors could be detected in earlier stages, amenable to curative treatments.     

Mouse models for investigating the underlying mechanisms of nonalcoholic steatohepatitis-derived hepatocellular carcinoma

As the incidence of hepatocellular carcinoma(HCC) caused by infection with the hepatotropic viruses hepatitis B and hepatitis C decreases, greater attention has become focused on HCC caused by nonalcoholic steatohepatitis(NASH), an advanced form of nonalcoholic fatty liver disease which has shown increasing prevalence in correspondence with the overall increase in metabolic syndrome over the recent decades. Several clinical population studies have shown a positive relationship between NASH and HCC, while also providing initial insights into the underlying mechanisms of HCC development from NASH. Research into the pathological progression of NASH to HCC has advanced by use of several beneficial rodent models. In this review, we summarize the established mouse models for preclinical research of NASH-associated HCC and discuss the underlying hepatic mechanisms of NASH-related tumorigenesis identified to date that could lead to new targets for treatment and prevention.     

不同空腹血糖水平与非酒精性脂肪性肝病的相关性研究

目的 探讨不同FPG水平与非酒精性脂肪性肝病(NAFLD)的相关性. 方法 选取7896名研究对象进行统一问卷调查、血液生化和肝脏超声检查,根据FPG水平将研究对象分为NGT、IFG和T2DM组,分析NAFLD影响因素. 结果 NGT、IFG、T2DM组NAFLD检出率分别为43.0％、63.0％和67.6％,IFG、T2DM组发生NAFLD的OR值分别是NGT组的1.31、1.77倍(95％CI:1.07～1.60、1.42～2.20,P＜0.01). 结论 IFG和T2DM是发生NAFLD的独立危险因素.     

Advances in hepatocellular carcinoma: Nonalcoholic steatohepatitis-related hepatocellular carcinoma

An increase in the prevalence of obesity and diabetes mellitus has been associated with the rise in nonalcoholic fatty liver disease (NAFLD). Two-thirds of the obese and diabetic populations are estimated to develop NAFLD. Currently, NAFLD is the most common etiology for chronic liver disease globally. The clinical spectrum of NAFLD ranges from simple steatosis, an accumulation of fat greater than 5% of liver weight, to nonalcoholic steatohepatitis (NASH), a more aggressive form with necroinflammation and fibrosis. Among the patients who develop NASH, up to 20% may advance to cirrhosis and are at risk for complications of end-stage liver disease. One of the major complications observed in patients with NASH-related cirrhosis is hepatocellular carcinoma (HCC), which has emerged as the sixth most common cancer and second leading etiology of cancer-related deaths worldwide. The incidence of HCC in the United States alone has tripled over the last three decades. In addition, emerging data are suggesting that a small proportion of patients with NAFLD may be at higher risk for HCC in the absence of cirrhosis - implicating obesity and diabetes mellitus as potential risk factors for HCC.