非酒精性脂肪性肝炎的无创诊断方法

非酒精性脂肪性肝病从发病率方面来看已成为全球第一大肝病,并且正在逐渐成为发达国家肝移植的是首位病因,其疾病谱包括单纯性脂肪肝、非酒精性脂肪性肝炎(NASH)、肝纤维化及肝硬化,与单纯性脂肪肝相比,NASH并非良性疾病,可发展为晚期肝硬化及肝癌。目前NASH诊断的金标准为肝活组织检查,但因有侵入性及潜在的并发症出现几率而限制了其广泛应用。目前临床上尝试采用非侵入性诊断方法替代肝穿刺活组织检查来诊断NASH,但尚缺乏成熟可靠的无创判定方法,因此仍需要不断努力探索改进。现将近年来国内外对NASH无创诊断方法的有关进展作一概述。     

非酒精性脂肪性肝病组学生物标志物的研究进展

非酒精性脂肪性肝病（NAFLD）是世界上最常见的慢性肝病之一,包括单纯性脂肪肝、非酒精性脂肪性肝炎、相关肝硬化和肝细胞癌。肝脏炎症坏死及纤维化程度与NAFLD患者的长期预后密切相关,故早期监测疾病进展和早期干预具有重要意义。肝组织活检仍然是诊断NAFLD的金标准,作为一项有创检查,肝组织活检不易在临床上广泛开展。随着组...     

非酒精性脂肪性肝病的诊断与评估

非酒精性脂肪性肝病(NAFLD)是临床最常见肝病之一，其发病率在全球范围内持续增加。NAFLD包括非酒精性肝脂肪变，并可以进一步进展为非酒精性脂肪性肝炎、肝硬化和肝细胞癌。迄今为止，肝活检被认为是评估肝脂肪变性和纤维化的“金标准”。但鉴于活检在大范围筛查中存在着局限性，用于评估NAFLD各个阶段的非侵入性测试对患者诊断及预后管理的作用显得愈发重要。本文总结了NAFLD诊断与评估的最新进展。     

罗格列酮在非酒精性脂肪性肝纤维化中的作用

非酒精性脂肪性肝病的病理过程包括单纯性脂肪肝、脂肪性肝炎、肝纤维化和肝硬化,脂肪性肝纤维化是该疾病进展为肝硬化的重要阶段,肝星状细胞(HSC)激活及表型转化是肝纤维化形成的中心环节.     

非酒精性脂肪性肝病的研究进展

非酒精性脂肪性肝病经历由非酒精性单纯性脂肪肝发展至非酒精性脂肪性肝炎和肝硬化或原发性肝癌的缓慢过程,并与心血管病的发生关系密切.本文针对非酒精性脂肪性肝病的流行病学、发病机制、诊断和治疗等的研究进展进行综述.     

影像技术在诊断非酒精性脂肪性肝病中的应用

非酒精性脂肪性肝病是一种与胰岛素抵抗和遗传易感性相关的代谢应激性肝疾病。其疾病谱包括:非酒精性单纯性脂肪肝、非酒精性脂肪性肝炎和其相关的肝硬化和肝细胞癌。该病起病隐匿,具有进展为肝纤维化、肝细胞癌倾向,因而早期诊断、早期治疗具有重要意义。目前肝活检仍是该病诊断的"金标准",但因其具有显著创伤性且价格较贵难以普及。普通的影像诊断技术如超声、CT、MRI等,仅对该病定性诊断有一定价值,但不能作出相应定量诊断,无法满足临床需求。随着影像和相关软件技术的进一步发展,使得定量诊断非酒精性脂肪性肝病成为可能。本文就影像技术诊断非酒精性脂肪性肝病的进展予以概述。     

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。     

非酒精性脂肪性肝病非侵人性诊断的研究及细胞角蛋白18的意义

此文主要介绍非酒精性脂肪性肝病(NAFLD)在临床、实验室研究中的非侵入性诊断方法,详细介绍细胞角蛋白18在非酒精性脂肪性肝炎与单纯性非酒精性脂肪肝鉴别诊断中的研究,以及运用细胞角蛋白18作为生物标志物在对NAFLD非侵入性诊断研究中所面临的挑战.     

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。     

脂肪肝是糖尿病的危险因素

非酒精性脂肪肝是指不饮酒或很少饮酒的人群中，除病毒性肝炎、药物性肝病、自身免疫性肝病、遗传性肝病等原因外，从单纯肝脏脂肪变性到非酒精性脂肪性肝炎，及部分患者最终进展为肝硬化的广谱脂肪性肝病。     

Non-invasive markers associated with liver fibrosis in non-alcoholic fatty liver disease

The diagnosis of fibrosis within liver disease is important for prognosis, stratification for treatment, and monitoring of treatment efficacy. The rising incidence and prevalence of non-alcoholic fatty liver disease (NAFLD) has driven the search for accurate non-invasive tools of liver fibrosis within this condition. With the aid of a systematic review, we explore how the field has evolved from the discovery of simple blood parameters to panel markers of liver fibrosis. We will discuss the biological plausibility, limitations, potential uses, and emerging diagnostic techniques of non-invasive markers in this rapidly expanding field.     

Controversy in the diagnosis of pediatric non-alcoholic fatty liver disease

In the last years childhood obesity has reached epidemic diffusion with about 200 million school-age children worldwide being overweight or obese. Simultaneously, also the prevalence of obesity comorbidities has been increased and the non-alcoholic fatty liver disease (NAFLD) has become the most common form of liver disease in childhood. Also if there are some not-invasive diagnostic possibilities, the diagnostic gold standard is represented by hepatic biopsy giving to the clinicians the possibility to both diagnose the NAFLD and evaluate its progression to fibrosis or cirrhosis with greater certainty than other techniques. The use of liver biopsy in clinical practice causes debate among health care providers. Most patients with NAFLD have a good prognosis and, therefore, the risks of a liver biopsy seem to outweigh the clinical benefits. It represents an impractical screening procedure because it is both expensive and invasive and, moreover, sampling error of liver biopsy can result in substantial misdiagnosis and staging inaccuracies because histological lesions of non-alcoholic steatohepatitis are unevenly distributed throughout the liver parenchyma. The liver biopsy limitations have led the clinicians to use, also if highly imperfect, non-invasive methods to diagnose and stage NAFLD. In this editorial the main diagnostic controversies in pediatric NAFLD are examined.     

Non-invasive assessment of fibrosis in non-alcoholic fatty liver disease (NAFLD)

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in Western countries, and its prevalence is increasing worldwide. It currently affects approximately 30% of adults and 10% of children and adolescents. The resulting increase in the number of patients with NAFLD is expected to translate into increased numbers of patients with liver cirrhosis, and hepatocellular carcinoma. In this context, it is particularly important to identify patients at risk for progressive chronic liver disease. Currently, liver biopsy is the gold standard to diagnose non-alcoholic steatohepatitis (NASH) and to establish the presence and stage of fibrosis. Due to the remarkable increase in the prevalence of NAFLD and the concomitant efforts in developing novel therapies for patients with NASH, non-invasive, simple, reproducible, and reliable noninvasive methodologies are needed. This paper provides a concise overview of the role of non-invasive diagnostic tools for the determination of presence and extent of fibrosis in NAFLD patients, with particular emphasis on the methods currently available in clinical practice.     

Liver fibrosis in non-alcoholic fatty liver disease-diagnostic challenge with prognostic significance

Non-alcoholic fatty liver disease(NAFLD) is the mostcommon liver disease in the Western world, with a prevalence of 20%. In a subgroup of patients, inflammation, ballooning degeneration of hepatocytes and a varying degree of fibrosis may develop, a condition named non-alcoholic steatohepatitis. Advanced liver fibrosis(stage F3) and cirrhosis(stage F4) are histologic features that most accurately predict increased mortality in both liver-related and cardiovascular diseases. Patients with advanced fibrosis or cirrhosis are at risk for complications such as hepatocellular carcinoma and esophageal varices and should therefore be included in surveillance programs. However, liver disease and fibrosis are often unrecognized in patients with NAFLD, possibly leading to a delayed diagnosis of complications. The early diagnosis of advanced fibrosis in NAFLD is therefore crucial, and it can be accomplished using serum biomarkers(e.g., the NAFLD Fibrosis Score, Fib-4 Index or BARD) or non-invasive imaging techniques(transient elastography or acoustic radiation force impulse imaging). The screening of risk groups, such as patients with obesity and/or type 2 diabetes mellitus, for NAFLD development with these non-invasive methods may detect advanced fibrosis at an early stage. Additionally, patients with a low risk for advanced fibrosis can be identified, and the need for liver biopsies can be minimized. This review focuses on the diagnostic challenge and prognostic impact of advanced liver fibrosis in NAFLD.     

Comments on validation of conventional non-invasive fibrosis scoring systems in patients with metabolic associated fatty liver disease

To evaluate and predict liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD), several non-invasive scoring systems were built and widely used in the progress of diagnosis and treatment, which showed great diagnostic efficiency, such as aspartate aminotransferase to platelet ratio index, fibrosis-4 index, body mass index, aspartate aminotransferase to alanine aminotransferase ratio, diabetes score and NAFLD fibrosis score. Since the new concept of metabolic associated fatty liver disease (MAFLD) was proposed, the clinical application value of the non-invasive scoring systems mentioned above has not been assessed in MAFLD. The evaluation of the diagnostic performance of these non-invasive scoring systems will provide references for clinicians in the diagnosis of MAFLD.     

Cardiovascular risk across the histological spectrum and the clinical manifestations of non-alcoholic fatty liver disease:an update

Non-alcoholic fatty liver disease(NAFLD) is considered to be an independent cardiovascular disease(CVD)risk factor. However, simple steatosis has a benign clinical course without excess mortality. In contrast, the advanced form of NAFLD, non-alcoholic steatohepatitis(NASH) with liver fibrosis increases mortality by approximately 70%, due to an increase in CVD mortality by approximately 300%. Chronic kidney disease(CKD) may be caused by NAFLD/NASH and it substantially increases CVD risk, especially in the presence of type 2 diabetes mellitus. Moreover, CKD may trigger NAFLD/NASH deterioration in a vicious cycle. NAFLD/NASH is also related to increased arterial stiffness(AS), an independent CVD risk factor that further raises CVD risk. Diagnosis of advanced liver fibrosis(mainly by simple non-invasive tests), CKD,and increased AS should be made early in the course of NAFLD and treated appropriately. Lifestyle measures and statin treatment may help resolve NAFLD/NASH and beneficially affect the CVD risk factors mentioned above.     

非酒精性脂肪性肝病显著肝纤维化的无创诊断

目的:通过对非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)患者多个肝纤维化非创伤性诊断模型的验证和分析比较,评价其诊断价值.方法:选取29例NAFLD患者,进行肝组织活检和病理学分期,并检测血清指标,用受试者操作特征(ROC)曲线等方法评估APRI指数、AST/ALT比率、BARD评分等模型的诊断价值.结果:29例病例中17例(58.9%)为男性,平均年龄(51±12)岁,平均体质量指数为(27±5)kg/m2,糖尿病患者15(51.7%);病理肝纤维化分级提示显著纤维化S3-S4:6例(20.6%).各诊断模型对肝脏显著纤维化程度都具有一定诊断价值,其中AST/ALT比率表现最佳[其曲线下面积(AUROC)为0.83],其次为BARD评分(AUROC0.77)和APRI指数(AUROC0.67).AST/ALT比率和BARD评分模型的阴性预测值均大于90%(分别为93%和95%).阳性预测值均处于中低等水平.AST/ALT比率和BARD评分模型分别可使68.9%和37.9%的患者避免肝活检.结论:肝纤维化非创伤性诊断模型能较好地区分存在显著肝纤维化的NAFLD患者,其中以AST/ALT比率、BARD评分模型较为有效,可以避免部分患者行肝穿刺检查.     

自噬在肝脏脂质代谢中的意义及其与胰岛素抵抗的关系

非酒精性脂肪性肝病(NAFLD)是一种与胰岛素抵抗、脂质代谢紊乱、慢性炎症以及遗传易感性强烈关联的获得性代谢应激性肝损伤,疾病谱包括单纯性脂肪肝、脂肪性肝炎及其相关纤维化、肝硬化。由于肥胖症和代谢综合征在全球的流行,近20年亚洲国家和地区NAFLD增长迅速,导致疾病谱变迁,NAFLD现已成为欧美发达国家(流行率17%~33%)以及我国经济较发达地区的第一大慢性肝病。近几年研究发现,自噬作为一种细胞程序,在介导脂质代谢过程中具有非常关键的作用,结合NAFLD的流行病学、发病机制,本文就自噬在肝脏脂质代谢中的作用意义及其与IR的关系研究现状作一综述。     

Overview and developments in noninvasive diagnosis of nonalcoholic fatty liver disease

High prevalence of non-alcoholic fatty liver disease (NAFLD) and very diverse outcomes that are related to disease form and severity at presentation have made the search for noninvasive diagnostic tools in NAFLD one of the areas with most intense development in hepatology today. Various methods have been investigated in the recent years, including imaging methods like ultrasound and magnetic resonance imaging, different forms of liver stiffness measurement, various biomarkers of necroinflammatory processes (acute phase reactants, cytokines, markers of apoptosis), hyaluronic acid and other biomarkers of liver fibrosis. Multicomponent tests, scoring systems and diagnostic panels were also developed with the purposes of differentiating non-alcoholic steatohepatitis from simple steatosis or discriminating between various fibrosis stages. In all of the cases, performance of noninvasive methods was compared with liver biopsy, which is still considered to be a gold standard in diagnosis, but is by itself far from a perfect comparative measure. We present here the overview of the published data on various noninvasive diagnostic tools, some of which appear to be very promising, and we address as well some of still unresolved issues in this interesting field.     

Pediatric Non-alcoholic Fatty Liver Disease

Childhood obesity has reached epidemic proportions, and by 2012, more than one third of American children were overweight or obese. As a result, increasingly, children are developing complications of obesity including liver disease. In fact, non-alcoholic fatty liver disease is the most common form of chronic liver disease seen in children today. Recently, there has been a burgeoning literature examining the pathogenesis, genetic markers, and role of the microbiome in this disease. On the clinical front, new modalities of diagnosing hepatic steatosis and hepatic fibrosis are being developed to provide non-invasive methods of surveillance in children. Lastly, the mainstay of treatment of pediatric non-alcoholic fatty liver disease (NAFLD) has been largely through lifestyle interventions, namely, dieting and exercise. Currently, there are a number of clinical trials examining novel lifestyle and drug therapies for NAFLD that are registered with the US National Institutes of Health ClinicalTrials.gov website.