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研究进展

非酒精性脂肪性肝炎 (Ｎｏｎ -ａｌｃｏｈｏｌｉｃｓｔｅａｔｏｈｅｐａｔｉｔｉｓ ,ＮＡＳＨ)是指肝组织病理学变化与酒精性脂肪性肝炎相似 ,但无明确饮酒史的一种慢性肝炎 ,是一种获得性代谢疾病[1] 。早在 1962年 ,Ｌｅｅｖｙ[2 ] 就发现某些患者的肝脏组织学病变与酒精性肝病无法鉴别 ,均有显著的脂肪沉积 ,故称为脂肪肝 (ｆａｔｔｙｌｉｖｅｒ) ,直到 1980年 ,Ｌｕｄｗｉｇ[3] 才称其为ＮＡＳＨ。近 2 0年来 ,人们对ＮＡＳＨ的研究日益受到重视 ,在美国整个人群中有 2 5%的肝功能异常患者 ,其中大部分可能属于此病 ,发病率仅次于ＨＣ…     

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病理临床观察

目的 观察非酒精性脂肪性肝炎的病理及临床特点。方法 经血清学、肝组织免疫组织化学和原位杂交检测，排除甲一戊型肝炎病毒感染的不明原因肝炎患者对其肝组织进行光镜观察，并对相应的临床资料进行了分析。结果 97例不明原因肝炎患者肝组织中检出非酒精性脂肪性肝炎15例(15．5％)。病变的特点是小叶内3区为主的大泡性脂肪变性，邻近的肝细胞呈气球样变。小叶内有弥漫的单个核和分叶核细胞浸润，以及窦周纤维化。肝组织的病变按Brunt标准进行了分级和分期后，计有7例GlS1，3例G2S2，4例G1S1，1例G3S2。其中14例患者有轻—中度的转氨酶升高，10例有高脂血症，8例患有糖尿病，9例于B超下检出脂肪肝。结论 非酒精性脂肪性肝炎是一种较为常见的、具有一定临床病理特点的原因不明性慢性肝病。     

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。     

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药物治疗

非酒精性脂肪性肝炎是非酒精性脂肪性肝病的一种,其可以进一步发展为终末期肝病以致肝功能衰竭。非酒精性脂肪性肝炎药物治疗主要包括二甲双胍、过氧化物酶体增殖物-γ激动剂、已酮可可碱、N-乙酰半胱氨酸、血管紧张素Ⅱ受体拮抗剂、熊去氧胆酸、维生素E、降脂药等。近年来,对这些药物治疗非酒精性脂肪性肝炎的疗效也做了相关研究,但均未得出确切的结论。     

Endpoints and clinical trial design for nonalcoholic steatohepatitis

Nonalcoholic fatty liver disease is a common cause of chronic liver disease in the general population. Nonalcoholic steatohepatitis (NASH), the aggressive form of nonalcoholic fatty liver disease, is associated with an increased risk of liver-related mortality and cardiovascular disease. At present, a liver biopsy is the only generally acceptable method for the diagnosis of NASH and assessment of its progression toward cirrhosis. Although several treatments have shown evidence of efficacy in clinical trials of varying design, there are no approved treatments for NASH, and published trials are often too divergent to allow meaningful comparisons. There is thus a lack of established noninvasive, point-of-care diagnostics and approved treatment on one hand and a substantial population burden of disease on the other. These provide the rationale for developing consensus on key endpoints and clinical trial design for NASH. CONCLUSION: This article summarizes the consensus arrived at a meeting of the American Association for the Study of Liver Diseases on the key endpoints and specific trial design issues that are germane for development of diagnostic biomarkers and treatment trials for NASH.     

非酒精性脂肪性肝炎临床特征及其危险因素分析

目的探讨非酒精性脂肪性肝炎（NASH）的临床特征及其危险因素。方法选取NASH患者76例和健康人84例,分析临床症状、生化和影像学指标。结果在76例患者中,体检发现者43例（56.6%）,有症状者33例（43.4%）;NASH组BMI、DBP、FPG、2hPPG、TG、ALT、ALT/AST、CRP、PLT与对照组比较有显著性差异（P〈0.05）;与NASH关系最密切的指标是BMI（OR=8.45）,其次分别是TG、2hPPG、FPG、DBP、年龄、病程（OR分别为3.70,2.83,2.61,2.10,1.41、1.20）。结论 NASH患者起病隐匿,多无明显的消化道症状,肥胖、高脂血症、糖尿病和高血压是发生NASH的主要危险因素。     

Steatosis and nonalcoholic steatohepatitis. A comparative analysis

Liver biopsies with a main histological diagnosis of steatosis were selected from 3,422 liver biopsies carried out in our department between January 1995 and December 1998. Patients with known risk factors for steatosis, such as excessive alcohol consumption, hepatitis C infection, treatment with amiodarone, perhexiline maleate, tamoxifen, antiviral drugs (didanosine, zidovudine) methotrexate, sodium valproate or total parenteral nutrition, Wilson's disease and organ transplant were subsequently excluded. Of the 43 liver biopsies finally included in the study, 23 showed simple steatosis and 20 steatohepatitis. Eighty-one per cent of the patients were male (mean age of 44 years) and the majority were asymptomatic. The most frequent indication for liver biopsy was hypertransaminasemia. No differences were observed between the two groups in terms of frequency and severity of classical risk factors for steatosis (diabetes mellitus, dyslipemia and obesity). Thirty-five percent of patients with steatohepatitis and 26% of those with simple steatosis had none of these risk factors. Patients with steatohepatitis were older than those with simple steatosis. They presented more severe symptomatology, the degree of steatosis was more intense and laboratory investigations showed greater alterations. These results suggest that simple steatosis and nonalcoholic steatohepatitis are two different phases of the same disease. The difficulty in clinical differentiation justifies carrying out liver biopsy, especially in patients with more severe symptomatology whose laboratory results show greater alterations, since these patients present more marked histological lesions, are at risk of developing liver cirrhosis and require therapy.     

环氧合酶与非酒精性脂肪性肝炎

环氧合酶(COX)是体内催化花生四烯酸分解为前列腺素(PG)的关键酶,它在多种组织和细胞的炎症过程和增殖中发挥重要作用.     

Alcoholic and nonalcoholic steatohepatitis

The constellation of histopathologic lesions that characterize alcoholic and nonalcoholic steatohepatitis has been well described and has served as the basis for clinical diagnosis, natural history studies, and experimental models for analyses of etiopathogenesis. The lesions common to both entities include, to varying degrees, steatosis, liver cell ballooning, lobular inflammation with a notable component of polymorphonuclear leukocytes, and a characteristic form of fibrosis that is initially located in the perisinusoidal regions of acinar zone 3. Cirrhosis with or without steatosis or steatohepatitis may occur in both entities. Mallory's hyaline is common but not necessary; megamitochondria and varying amounts of iron may be observed in either process. Hepatocellular carcinoma is a recognized complication of both processes, albeit with greater frequency in the former. Alcoholic hepatitis may present with more severe clinical and histologic manifestations than the nonalcoholic counterpart, including significant morbidity and mortality. The perivenular lesions collectively referred to as sclerosing hyaline necrosis are markers of severity, and are not common in nonalcoholics. In many instances, however, the microscopic lesions of these two processes are similar, likely as a reflection of common pathogenetic pathways, and the distinction between the two is ultimately clinically derived.     

Pathophysiology of nonalcoholic steatohepatitis

Nonalcoholic fatty liver disease (NAFLD) affects approximately 30% of adults and 20% of children in the United States. Nonalcoholic steatohepatitis (NASH) is its most severe histologic form and progresses to cirrhosis in 20% of these patients. Once developed, 30% to 40% of patients with NASH cirrhosis will experience a liver-related death. Consequently, it has become extremely important to understand the pathophysiology of NASH to develop sound therapeutic interventions. It is now recognized that nonhepatic mechanisms are largely responsible for the development of insulin resistance, which causes hepatic steatosis. Once developed, oxidative stress and diminished antioxidants within the liver initiate the progression from steatosis alone to NASH and ultimately to cirrhosis. However, not all patients progress to cirrhosis. As is the case for other common complex metabolic diseases, it is the interaction between the environment and genetics that will determine the phenotypic expression of NAFLD and NASH in each individual patient. Which of the pathophysiologic factors (which are discussed in this review), either alone or in combination, will eventually provide the basis for the most effective therapy has yet to be determined.