非酒精性脂肪性肝病无创诊断研究进展

非酒精性脂肪性肝病是全球最常见的慢性肝病。据估计,全球约25%的成年人患有非酒精性脂肪性肝病,且患病率逐年增加。非酒精性脂肪性肝病的疾病谱涵盖非酒精性脂肪肝、非酒精性脂肪性肝炎、非酒精性脂肪性肝炎相关纤维化、肝硬化和肝细胞癌。肝活检作为非酒精性脂肪性肝病诊断和分期的“金标准”,因有创性、取样变异和评价不一致等局限性限制了其广泛应用。随着进展为非酒精性脂肪性肝炎的患者数量增加,特别是疾病严重程度较重的病人增多,临床上迫切需要有效治疗药物,也迫切需要开发无创标志物来筛查、诊断、监测患者和判断疗效。对非酒精性脂肪性肝病的无创诊断研究进展进行综述,包括对脂肪变的评估、非酒精性脂肪性肝炎的诊断和纤维化的评估。     

肝脏非实质细胞在非酒精性脂肪性肝炎中的作用研究进展

非酒精性脂肪性肝病是全球最流行的肝脏疾病,其疾病谱包含非酒精性脂肪肝、非酒精性脂肪性肝炎、与非酒精性脂肪性肝炎相关的纤维化、肝硬化和肝细胞癌。非酒精性脂肪性肝炎是非酒精性脂肪性肝病进展性的肝脏病理表征,临床上需要药物治疗或其他治疗方式干预,但目前全球尚无针对非酒精性脂肪性肝炎的药物获批上市。非酒精性脂肪性肝炎发病机制复杂,涉及多种细胞内、细胞间的交互作用以及复杂的分子信号通路。非酒精性脂肪性肝炎治疗是一个尚未被满足的巨大临床需求。综述了肝脏中几种主要的非实质细胞在非酒精性脂肪性肝炎发病中的重要作用,同时探讨了非酒精性脂肪性肝炎药物开发靶点与不同细胞之间的相关性。     

非酒精性脂肪性肝病的治疗

非酒精性脂肪性肝病(BAFLD)又称非酒精性脂肪肝,是一类肝组织学改变,与酒精性肝病相似,但无过量饮酒史的临床病理综合征,包括单纯性脂肪肝、非酒精性脂肪性肝炎(NASH)和脂肪性肝硬化,其中NASH不仅可使肝酶持续异常,而且可导致失代偿期肝硬化、肝细胞癌以及肝功能衰竭,目前已成为仅次于慢性病毒性肝炎、酒精性肝病的重要肝硬化前期病变之一。     

非酒精性脂肪性肝炎内科综合治疗临床观察

随着生活水平的提高,脂肪肝尤其是非酒精性脂肪性肝病日益增加,非酒精性脂肪性肝炎是非酒精性脂肪性肝病中的一种临床类型。我们探讨内科综合治疗对非酒精性脂肪性肝炎的疗效。1资料与方法1.1一般资料2006年3月至2007年6月消化科就诊的非酒精性脂肪性肝炎患者,将患者采取随机编     

非酒精性脂肪肝的诊疗现状及展望

<正>非酒精性脂肪肝(NAFL),又称非酒精性脂肪性肝病(NAFLD),是近来被广泛认识的慢性肝病,是一种无过量饮酒史、肝实质细胞脂肪变性和脂肪贮积为特征的临床病理综合征。非酒精性脂肪性肝炎(NASH)可逐渐进展为肝硬化、肝癌等终末期肝病,已成为目前仅次于慢性病毒性肝     

非酒精性脂肪性肝病不容忽视

非酒精性脂肪性肝病是一种与胰岛素抵抗及遗传等密切相关的代谢应激性肝脏损伤,其病理学改变与酒精性肝病相似,但患者无过量饮酒史。非酒精性脂肪性肝病包括：非酒精性单纯性脂肪肝、非酒精性脂肪性肝炎及其相关肝硬化和肝细胞癌。     

非酒精性脂肪性肝炎46例临床分析

非酒精性脂肪性肝病(NAFLD)是遗传—环境—代谢应激相关性疾病,包括非酒精性单纯性脂肪肝(NAFL)及由其演变的非酒精性脂肪性肝炎(NASH)和脂肪肝性肝硬化三种类型。近年来,由于生活方式的改变,环境因素的影响,糖尿病、高脂血症、肥胖的发病率升高,NAFL和NASH相继增多,本文就46例NASH的临床特点报告如下。1资料与方法本文46例均为2004年12月至2006年4月我院消化科门诊及病房诊治病例,其中男性32例,女性14例,年龄24-61岁,平均39岁。临床诊断均符合中华医学会肝病学分会脂肪肝酒精性肝病学组制定的非酒精性脂肪性肝病诊断标准,并排除…     

重度肥胖与非酒精性脂肪性肝病

非酒精性脂肪性肝病是发生于无明显饮酒的常见慢性肝病。包括单纯性脂肪肝、脂肪性肝炎、肝纤维化及肝硬化。研究证实，肥胖、糖尿病及高脂血症等是非酒精性脂肪性肝病形成的危险因素，其中肥胖是最重要的危险因素。而重度肥胖与非酒精性脂肪性肝病关系更密切。     

选择性COX-2抑制剂、PPARγ激动剂在非酒精性脂肪肝病中应用的研究进展

非酒精性脂肪性肝病是临床最常见的慢性肝病,以肝细胞脂肪变为主要特征,可逐渐进展为脂肪性肝炎、肝纤维化甚至肝硬化、肝癌。近年来,选择性环氧合酶-2(Cyclooxygenase-2,COX-2)抑制剂及PPARγ激动剂与非酒精性脂肪性肝病的关系受到关注。过氧化物酶体增殖物激活受体-γ(PPARγ)可能通过与COX-2相互作用,参与非酒精性脂肪性肝病的发病过程。现将选择性COX-2抑制剂及PPARγ激动剂在非酒精性脂肪性肝病中的应用做一综述。     

非酒精性脂肪性肝病的诊断

非酒精性脂肪性肝炎（NASH）是指病理上与酒精性肝炎相类似但无过量饮酒史的临床综合征，患者通常存在胰岛素抵抗及其相关代谢紊乱。当代谢性肝病的病理学特征不明或泛指整个脂肪性肝病的疾病谱时，通常使用非酒精性脂肪性肝病（NAFLD）这一术语，后者尚包括单纯性肝脂肪变或伴小叶内炎症，但没有肝细胞气球样变和纤维化，或仅伴孤立性门脉周围纤维化，以及无明显脂肪性肝炎的隐源性肝硬化等情况。随着社会经济的发展，NASH/NAFLD已成为重要的肝病之一，严重危害人类的健康。     

Promising therapies for treatment of nonalcoholic steatohepatitis

Introduction: Non-alcoholic fatty liver disease (NAFLD) has become the most common etiology for abnormal aminotransferase levels and chronic liver disease. Its growing prevalence is largely linked to the presence of metabolic syndrome, particularly diabetes and insulin resistance. It is estimated that 60–80% of the type 2 diabetic population has NAFLD. NAFLD encompasses a range of conditions ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). A subset of patients with hepatic steatosis progress to NASH, while 15–20% of patients with NASH develop cirrhosis. This progression is thought to be multifactorial, and there are currently no FDA-approved medications for the treatment of NASH.

Areas covered: We review drugs currently in Phase II and III clinical trials for treatment of NAFLD and NASH, including their mechanisms of action, relationship to the pathophysiology of NASH, and rationale for their development.

Expert opinion: The treatment of NASH is complex and necessitates targeting a number of different pathways. Combination therapy, preferably tailored toward the disease stage and severity, will be needed to achieve maximum therapeutic effect. With multiple agents currently being developed, there may soon be an ability to effectively slow or even reverse the disease process in many NAFLD/NASH patients.     

Review article: current management of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis

Background  Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome.
Aim  To assess the epidemiological impact and the current management of patients with NAFLD.
Methods  Published peer-reviewed literature and abstracts concerning NAFLD and non-alcoholic steatohepatitis (NASH) were reviewed. Articles specifically related to epidemiology, diagnosis and current treatment strategies for NAFLD and NASH are summarized.
Results  NAFLD is strongly associated with the epidemic of obesity and type-2 diabetes mellitus, and is estimated to affect about 20–30% of the population in the US. From the spectrum of NAFLD, only patients with biopsy-proven NASH (estimated prevalence in the US population is about 3–5%) have been convincingly shown to progress to cirrhosis, liver failure and hepatocellular carcinoma. The clinical manifestation of NAFLD is usually absent or subtle, with abnormal aminotransferases or incidental radiographic findings of fatty liver. The pathogenesis of NAFLD is attributed to a multi-hit process involving insulin resistance, oxidative stress, apoptotic pathways, and adipocytokines. In 2008, there is no established treatment for NAFLD. Weight loss and treatment for each component of metabolic syndrome. Nevertheless, a large number of agents are being considered in clinical trials of patients with NASH.
Conclusions  Awareness of the tremendous impact of NAFLD as an important cause of chronic liver disease is increasing along with a great deal of information about its pathogenesis. Future, well-designed clinical trials that target specific pathways involved in the pathogenesis of NASH are urgently needed.     

血清瘦素水平与非酒精性脂肪性肝病相关性研究

目的探讨非酒精性脂肪性肝病（NAFLD）患者血清瘦素（LEP）水平及其在“二次打击”发病机制中的作用。方法选择单纯NAFLD患者43例,非酒精性脂肪性肝炎（NASH）患者41例以及健康对照组40例,测定并比较空腹LEP水平。采用稳态胰岛素评价指数（HOMA）评价胰岛素抵抗程度,丙二醛（MDA）评价脂质过氧化程度,血清Ⅲ型前胶原肽（PCHI）、Ⅳ型胶原（IV-C）、层粘连蛋白（LN）、透明质酸（HA）作为肝纤维化指标。分析NAFLD患者中LEP与胰岛素抵抗及脂质过氧化程度、肝纤维化的关系。结果单纯NAFL组HOMA、LEP值高于对照组,单纯NAFL患者MDA、PCⅢ、Ⅳ-C、LN、HA与对照组比较差异无统计学意义,NASH患者HOMA、LEP、MDA、PCIII、1V-C、LN、HA明显高于对照组及单纯NAFL组,单纯NAFL及NASH患者LEP与HOMA值呈正相关,NASH患者LEP水平与MDA及肝纤维化血清学指标PCⅢ、IV—C、LN、HA呈正相关。结论LEP与NAFLD的发病机制有关,是“初次打击”胰岛素抵抗诱发脂肪肝的中介激素,LEP参与调节NAFLD的炎性反应,促使脂肪肝发展为脂肪性肝炎,LEP为NAFLD发病机制中“二次打击”（炎症．坏死循环）的致病因子之一;从而促进肝纤维化的发生。并可能是导致肝纤维化的始动因子之一。     

Systematic review: the diagnosis and staging of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis

Aliment Pharmacol Ther 2011; 33: 525–540

Summary

Background Non‐alcoholic fatty liver disease (NAFLD) has become the most prevalent cause of liver disease in Western countries. The development of non‐alcoholic steatohepatitis (NASH) and fibrosis identifies an at‐risk group with increased risk of cardiovascular and liver‐related deaths. The identification and management of this at‐risk group remains a clinical challenge. Aim To perform a systematic review of the established and emerging strategies for the diagnosis and staging of NAFLD. Methods Relevant research and review articles were identified by searching PubMed, MEDLINE and EMBASE. Results There has been a substantial development of non‐invasive risk scores, biomarker panels and radiological modalities to identify at‐risk patients with NAFLD without recourse to liver biopsy on a routine basis. These modalities and algorithms have improved significantly in their diagnosis and staging of fibrosis and NASH in patients with NAFLD, and will likely impact on the number of patients undergoing liver biopsy. Conclusions Staging for NAFLD can now be performed by a combination of radiological and laboratory techniques, greatly reducing the requirement for invasive liver biopsy.     

Are statins ‘IDEAL’ for non-alcoholic fatty liver disease?

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and cause of elevated serum liver enzyme activities in the developed world1. Obesity, diabetes mellitus (DM), and dyslipidaemia, common components of the metabolic syndrome (MetS), are frequently associated with NAFLD; 75–100% of patients with MetS or DM have NAFLD2. NAFLD is characterized by hepatic triglyceride (TG) infiltration in the absence of alcohol abuse or chronic liver disease1. NAFLD includes a spectrum of conditions varying from steatosis to steatosis with inflammation [steatohepatitis (NASH)], necrosis, fibrosis or cirrhosis that rarely progresses to hepatocellular carcinoma3. NAFLD and NASH are the hepatic manifestations of MetS and are associated with increased cardiovascular disease (CVD) risk4. Most NAFLD/NASH patients die from CVD rather than from liver disease4,5. There is no universally accepted treatment for NAFLD1-5.     

Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults

Aliment Pharmacol Ther 2011; 34: 274–285

Summary

Background Non‐alcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease, and its worldwide prevalence continues to increase with the growing obesity epidemic. This study assesses the epidemiology of NAFLD in adults based on clinical literature published over the past 30 years. Aim To review epidemiology and natural history of non‐alcoholic fatty liver disease and non‐alcoholic steatohepatitis in adults based on clinical literature published over the past 30 years. Methods An in‐depth search of PubMed (1980–2010) was based on five search terms: ‘non‐alcoholic fatty liver disease’ OR ‘non‐alcoholic steatohepatitis’ OR ‘fatty liver’ OR ‘steatosis’ AND ‘incidence’ [MeSH Terms] OR ‘prevalence’ [MeSH Terms] OR ‘natural history’. Studies of paediatric cohorts were excluded. Articles were categorised by topic and summarised, noting generalisations concerning their content. Results Four study categories included NAFLD incidence, prevalence, risk factors and natural history. Studies related to NAFLD prevalence and incidence indicate that the diagnosis is heterogeneous and relies on a variety of assessment tools, including liver biopsy, radiological tests such as ultrasonography, and blood testing such as liver enzymes. The prevalence of NAFLD is highest in populations with pre‐existing metabolic conditions such as obesity and type II diabetes. Many studies investigating the natural history of NAFLD verify the progression from NASH to advanced fibrosis and hepatocellular carcinoma. Conclusions Non‐alcoholic fatty liver disease is the most common cause of elevated liver enzymes. Within the NAFLD spectrum, only NASH progresses to cirrhosis and hepatocellular carcinoma. With the growing epidemic of obesity, the prevalence and impact of NAFLD continues to increase, making NASH potentially the most common cause of advanced liver disease in coming decades.     

Toward a biochemical diagnosis of NASH: insights from pathophysiology for distinguishing simple steatosis from steatohepatitis

With the continuing epidemics of obesity and diabetes, nonalcoholic fatty liver disease (NAFLD) has received increased attention. Great efforts are being undertaken to improve the noninvasive diagnosis of NAFLD, with the ultimate goal of optimizing treatment options and clinical outcomes. Research suggests that blood-borne biochemical markers can be used to distinguish simple steatosis from nonalcoholic steatohepatitis (NASH), thus reducing the need of liver biopsy. Future developments in the field of diagnostic biochemistry within the spectrum of NAFLD can make this approach ideal for screening and monitoring purposes. In this review, we provide an overview of the different blood-borne markers which have been recently proposed for differentiating simple steatosis from NASH. We will also consider the practical and statistical issues that seem to be limiting the effective integration of biomarkers into clinical development.     

Present and future therapeutic strategies in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is found in individuals who do not drink or abuse alcohol and represents a significant health burden for the general community. NAFLD is often associated with one or more features of the metabolic syndrome and has potential for evolution towards non-alcoholic steatohepatitis (NASH), the necro-inflammatory form of liver steatosis. The most worrisome evolutive events in a subgroup of NASH patients include advanced liver fibrosis, cirrhosis, and hepatocellular carcinoma. Pathophysiology of NAFLD/NASH is complex, but studies point to a pre-eminent role of oxidative stress and lipid peroxidation in the liver, including early mitochondrial dysfunction. Changes follow an insulin resistance status with a background of a chronic pro-inflammatory status due to an excess of visceral adiposity. Although no established therapy exists for NAFLD/NASH, potential therapeutic approaches are discussed in this review.