单纯性非酒精性脂肪肝与非酒精性脂肪性肝炎临床特征比较

目的 探讨单纯性非酒精性脂肪肝（NAFL）与非酒精性脂肪性肝炎（NASH）患者临床相关因素的异同点.方法 收集2006年6月～2010年6月间我院住院及门诊资料完整的非酒精性脂肪性肝病（NAFLD）患者150例,其中非酒精性脂肪性肝炎65例,非酒精性脂肪肝85例,比较两组患者年龄、体重指数（BMI）、临床表现、实验室检查和合并症等因素.结果 非酒精性脂肪性肝炎组患者BMI、血清铁蛋白、IV型胶原、空腹胰岛素、空腹血糖、胰岛素抵抗指数、代谢综合症等相关疾病的发生率较非洒精性脂肪肝组明显增多,差异有显著性（P〈0.05）,其余指标比较差异无显著性.结论 非酒精性脂肪肝组与非酒精性脂肪性肝炎组患者非特异性症状（如疲劳、乏力等）的发生率及肝功能比较尤显著性差异;非酒精性脂肪性肝炎组并发症（如2型糖尿病等）较非洒精性脂肪肝组突出;非酒精性脂肪性肝炎组BMI、血清铁蛋白、Ⅳ型胶原、空腹血糖、空腹胰岛素、胰岛素抵抗指数等血清学指标较非酒精性脂肪肝组显著升高.     

非酒精性脂肪性肝炎的诊断

非酒精性脂肪性肝炎（NASH）是非酒精性脂肪性肝病（NAFLD）的一种类型,是非酒精性脂肪肝（NAFL）进展为肝纤维化和肝硬化的重要中间阶段。及早诊断NASH并进行干预,可以改善NAFLD患者的预后。但目前国内外尚无统一的诊断标准。多数NASH患者无或仅有轻微的临床症状,由于检测手段的局限性,很难依靠某一种方法准确诊断NASH。只有根据病史、实验室、影像学和病理学检查,同时结合无创诊断模型等进行综合评估,才能得出准确的诊断。     

非酒精性脂肪性肝炎诊断的研究进展

疾病的诊断均从问病史开始,体检、生物化学指标的检测、影像诊断、组织学检查等.体重指数和腰臀比例可作为NAFLD发生的有效预测指标,血糖、血脂常规检查也有助于诊断,但有200左右的NAFLD患者在确诊时,体重.血脂、血糖均在正常范围.     

非酒精性脂肪肝／非酒精性脂肪性肝炎是代谢综合征的一个表现

问：什么叫非酒精性脂肪肝／非酒精性脂肪性肝炎（NAFLD／NASH）？     

非酒精性脂肪性肝炎的治疗

非酒精性脂肪肝可以是一个独立的疾病 ,但更多见于全身性疾患在肝脏的病理过程。肥胖症、药物和毒物中毒、营养不良、糖尿病、妊娠、肝炎病毒或其他病原体感染以及先天性代谢缺陷等都可引起非酒精性脂肪肝。·本病在组织学上有与酒精性肝病类似的表现 ,肝活检显示从轻度的脂肪性肝炎至重度肝纤维化和肝硬化不同的组织学特征。·非酒精脂肪性肝炎诊断一般依据Ｐｏｗｅｌｌ等建议的标准 ,即①肝活检标本显示伴有炎症的中～重度大泡性脂肪变性 ,可伴或不伴有Ｍａｌｌｏｒｙ小体、纤维化或肝硬化 ;②无饮酒史或饮酒每周 <4 0克 ,随机检测血乙醇…     

非酒精性脂肪性肝炎的诊治进展

我国已有非酒精性脂肪性肝病（NAFLD）的诊疗指南（下称指南）,指南将该病分为非酒精性单纯性脂肪肝、非酒精性脂肪肝炎（NASH）及NASH相关肝硬化。1998年Day等发现NASH可发展为肝纤维化和肝硬化,NASH才获学术界与临床医师极大的关注,指南中指出单纯性脂肪肝的肝功能基本正常,而NASH存在代谢综合征或不明原因血清AIJT升高持续4周以上,但发现不升高也常见。近年人们更多的重视NASH的诊治,并取得一定的成果,本文扼要介绍近年来这方面诊治进展,供参考。     

非酒精性脂肪性肝炎的临床病理研究

目的：探讨非酒精性脂肪性肝炎（Nonalcoholic steatohepatitis,NASH)的临床和病理学特征。方法：对40例NASH患者的临床资料和穿刺肝组织进行临床和病理学分析,并与酒精性脂肪性肝炎（Alcoholic steatohepatitis,ASH)和丙型肝炎（HCV）患者各20例作对照。结果：90％ NASH患者肥胖（P＜0．01）,血浆总蛋白平均水平高于ASH（P＜0．05）,血清ALT、AST、GGT、TBA、TG平均水平分别是正常范围上限值的2．6、1．5、1．2、1．3倍,但白蛋白水平是正常范围下限值的0．96倍。NASH的组织学改变类似ASH,但有些组织学改变如脂肪变性、汇管区的炎症程度,Mallory小体和空泡状核的出现频率等两者间存在着差异性（P＜0．05或P＜0．01）。NASH有其相对的病理特征：大小泡混合型脂肪变性,以大泡为主;肝组织气球样变性,小叶中央区较常见,气球样变性的细胞胞浆内常常有嗜碱性的细颗粒;肝小叶内炎症,不典型的Mallory小体,汇管区周围易见空泡状核细胞。多数NASH患者的肝小叶中央区（腺泡Ⅲk带）有不同程度的窦周纤维化。结论：结果显示NASH有一些相对的临床和病理学特征,临床、病理及实验室检查相结合能对NASH作出肯定的诊断,其中病理活检仍然是诊断NASH的“金标准”。     

非酒精性脂肪性肝炎

非酒精性脂肪性肝炎具有与酒精性肝炎相似的组织学表现，但具有不同的发病机制和预后，本就这两方面作一综述。     

非酒精性脂肪性肝炎发病机制的实验研究

目的：通过建立大鼠非酒精性脂肪性肝炎（NASH）动物模型,探讨NASH的发病机制。方法：通过持续12周的高脂肪、高胆固醇饮食建立大鼠NASH模型,造模结束时检测模型组及正常组血清转氨酶、游离脂肪酸（FFA）;测定肝匀浆丙二醛（MDA）、超氧化物歧化酶（SOD）、FFA;用免疫组化法标记肝组织细胞色素P450ⅡE1（CYPⅡE1）及溶菌酶（LYZ）免疫阳性细胞－Kupffer细胞。结果：造模大鼠存在血清和肝匀浆FFA升高,肝匀浆脂质过氧化终产物MDA增加,而抗氧化物质SOD减少,肝组织免疫组化示CYPⅡE1呈高表达,Kupffer细胞明显增多。相关分析表明：随着FFA的增加,CYPⅡE1表达增高,脂质过氧化损伤亦增强,并且肝脏炎症、坏死加剧。结论：FFA在NASH的发病机制中起着重要作用;FFA的增加及其所引起的一系列CYPⅡE1高表达、Kupffer细胞激活以及脂质过氧化损伤,共同导致NASH以及肝细胞坏死。     

非酒精性脂肪性肝病和非酒精性脂肪性肝炎的无创性诊断

非酒精性脂肪性肝病（NAFLD）在美国和世界上许多其他地区都是最常见的慢性肝病．其患病率持续上升,目前美国约1,4的成人和10％的儿童患NAFLD。NAFLD包括多种疾病状态,从通常呈良性、非进展性临床过程的单纯性脂肪肝直至更为严重的、可进展为肝硬化和终末期肝病的非酒精性脂肪性肝炎（NASH）。目前．NASH的诊断依赖于创伤性肝活检,而肝活检存在取样和读片误差的缺陷。NASH的临床危险因素包括糖尿病和代谢综合征．但这些因素本身不足以预测NASH。常规肝酶水平预测可靠性低,新型血浆肝细胞死亡标记物单独或与临床危险因素联合今后可能成为无创性诊断工具。本文对无创性诊断工具在鉴别单纯性脂肪肝与NASH以及确定肝纤维化的存在及其范围中的作用作一概述．     

无创诊断和评估非酒精性脂肪性肝炎研究进展*

非酒精性脂肪性肝病（NAFLD）主要包括单纯性脂肪肝（NAFL)、非酒精性脂肪性肝炎（NASH）、相关肝硬化和肝细胞癌。相对于NAFL,NASH更易发展为肝硬化和肝癌,故早期诊断并对其干预尤为重要。近年来,多项无创诊断方法的出现致力于替代肝脏穿刺活检,主要包括血清学和影像学检查等,本文就无创性诊断和评估NASH作一综述。     

改良蛋氨酸胆碱缺乏饮食喂养的非酒精性脂肪性肝炎大鼠模型的建立

目的:观察改良蛋氨酸胆碱缺乏饮食(MCD)建立的脂肪性肝炎大鼠模型肝脏的脂肪变性和炎症情况.方法:大鼠26只随机分为4组,分别喂养MCD饮食和胆碱添加饮食(CS).3-8wk后处死,肝脏标本在甲醛中固定和石蜡包埋.HE染色和Masson染色后对脂肪变性、炎症和纤维化进行评分.血清ALT,AST,CH,LDL等指标通过生化分析仪进行测定.结果:MCD喂养组3wk可以看见肝脂肪变性和炎症,肝指数显著增加,ALT和AST显著升高,8wk可见纤维形成.结论:可通过改良的蛋氨酸胆碱缺乏(MCD)饮食建立非酒精性脂肪肝动物模型.     

Liver fibrosis markers of nonalcoholic steatohepatitis

Nonalcoholic fatty liver disease (NAFLD) is one of the major causes of chronic liver injury. NAFLD includes a wide range of clinical conditions from simple steatosis to nonalcoholic steatohepatitis (NASH), advanced fibrosis, and liver cirrhosis. The histological findings of NASH indicate hepatic steatosis and inflammation with characteristic hepatocyte injury (e.g., ballooning degeneration), as is observed in the patients with alcoholic liver disease. NASH is considered to be a potentially health-threatening disease that can progress to cirrhosis. A liver biopsy remains the most reliable diagnostic method to appropriately diagnose NASH, evaluate the severity of liver fibrosis, and determine the prognosis and optimal treatment. However, this invasive technique is associated with several limitations in routine use, and a number of biomarkers have been developed in order to predict the degree of liver fibrosis. In the present article, we review the current status of noninvasive biomarkers available to estimate liver fibrosis in the patients with NASH. We also discuss our recent findings on the use of the glycated albumin-to-glycated hemoglobin ratio, which is a new index that correlates to various chronic liver diseases, including NASH.     

Noninvasive evaluation of nonalcoholic fatty liver disease: Current evidence and practice

With the increasing number of individuals with diabetes and obesity,nonalcoholic fatty liver disease(NAFLD) is becoming increasingly prevalent,affecting one-quarter of adults worldwide. The spectrum of NAFLD ranges from simple steatosis or nonalcoholic fatty liver(NAFL) to nonalcoholic steatohepatitis(NASH). NAFLD, especially NASH, may progress to fibrosis, leading to cirrhosis and hepatocellular carcinoma. NAFLD can impose a severe economic burden,and patients with NAFLD-related terminal or deteriorative liver diseases have become one of the main groups receiving liver transplantation. The increasing prevalence of NAFLD and the severe outcomes of NASH make it necessary to use effective methods to identify NAFLD. Although recognized as the gold standard, biopsy is limited by its sampling bias, poor acceptability, and severe complications, such as mortality, bleeding, and pain. Therefore, noninvasive methods are urgently needed to avoid biopsy for diagnosing NAFLD. This review discusses the current noninvasive methods for assessing NAFLD,including steatosis, NASH, and NAFLD-related fibrosis, and explores the advantages and disadvantages of measurement tools. In addition, we analyze potential noninvasive biomarkers for tracking disease processes and monitoring treatment effects, and explore effective algorithms consisting of imaging and nonimaging biomarkers for diagnosing advanced fibrosis and reducing unnecessary biopsies in clinical practice.     

Promising diagnostic biomarkers of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: From clinical proteomics to microbiome

Fatty liver has been present in the lives of patients and physicians for almost two centuries. Vast knowledge has been generated regarding its etiology and consequences, although a long path seeking novel and innovative diagnostic biomarkers for nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) is still envisioned. On the one hand, proteomics and lipidomics have emerged as potential noninvasive resources for NAFLD diagnosis. In contrast, metabolomics has been able to distinguish between NAFLD and NASH, even detecting degrees of fibrosis. On the other hand, genetic and epigenetic markers have been useful in monitoring disease progression, eventually functioning as target therapies. Other markers involved in immune dysregulation, oxidative stress, and inflammation are involved in the instauration and evolution of the disease. Finally, the fascinating gut microbiome is significantly involved in NAFLD and NASH. This review presents state-of-the-art biomarkers related to NAFLD and NASH and new promises that could eventually be positioned as diagnostic resources for this disease. As is evident, despite great advances in studying these biomarkers, there is still a long path before they translate into clinical benefits.     

非酒精性脂肪性肝炎肝硬化发病机制研究进展与展望

正在过去几十年里,非酒精性脂肪性肝病(NAFLD)的发病率迅速增加。NAFLD包括单纯性脂肪肝(SFL)和非酒精性脂肪性肝炎(NASH)两种。SFL一般是指单纯肝细胞的脂肪积累,并无肝组织的炎症和坏死,但随着时间的推移和认识的提高,发现它与代谢综合征及2型糖尿病关系密切。值得注意的是在一定条件下,如肥胖、胰岛素抵抗、细胞因子(脂联素、瘦素、TNF-α、SREBP、MLCK、RBP4、性激     

Limitations of liver biopsy and non-invasive diagnostic tests for the diagnosis of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

It is estimated that 30%of the adult population in Japan is affected by nonalcoholic fatty liver disease(NAFLD).Fatty changes of the liver are generally diagnosed using imaging methods such as abdominal ultrasonography(US)and computed tomography(CT),but the sensitivity of these imaging techniques is low in cases of mild steatosis.Alanine aminotransferase levels may be normal in some of these patients,warranting the necessity to establish a set of parameters useful for detecting NAFLD,and the more severe form of the disease,nonalcoholic steatohepatitis(NASH).Although liver biopsy is currently the gold standard for diagnosing progressive NASH,it has many drawbacks,such as sampling error,cost,and risk of complications.Furthermore,it is not realistic to perform liver biopsies on all NAFLD patients.Diagnosis of NASH using various biomarkers,scoring systems and imaging methods,such as elastography,has recently been attempted.The NAFIC score,calculated from the levels of ferritin,fasting insulin,and typeⅣcollagen 7S,is useful for the diagnosis of NASH,while the NAFLD fibrosis score and the FIB-4 index are useful for excluding NASH in cases of advanced fibrosis.This article reviews the limitations and merits of liver biopsy and noninvasive diagnostic tests in the diagnosis of NAFLD/NASH.     

Histopathology of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

Nonalcoholic fatty liver disease (NAFLD), a hepatic manifestation of metabolic syndrome, is the most common chronic liver disease, and the prevalence is rapidly increasing worldwide. Nonalcoholic steatohepatitis (NASH), the severe form of NAFLD, can progress to liver cirrhosis and hepatocellular carcinoma (HCC). Although noninvasive clinical scores and image-based diagnosis for NAFLD have improved, histopathological evaluation of biopsy specimens remains the gold standard for diagnosing NAFLD/NASH. Steatosis, lobular inflammation, and hepatocellular ballooning are all necessary components for the diagnosis of NASH; fibrosis is also typically observed. Other histopathological abnormalities commonly observed in NASH include hepatocellular glycogenated nuclei, lipogranulomas, and acidophil bodies. The characteristics of pediatric NAFLD/NASH differ from adult NAFLD/NASH. Specifically, steatosis and portal inflammation are more severe in pediatric NAFLD, while intralobular inflammation and perisinusoidal fibrosis are milder. Although interobserver agreement for evaluating the extent of steatosis and fibrosis is high, agreement is low for intralobular and portal inflammation. A recently reported histological variant of HCC, steatohepatitic HCC (SH-HCC), shows features that resemble non-neoplastic steatohepatitis, and is thought to be strongly associated with underlying NASH. In this report, we review the histopathological features of NAFLD/NASH.