Non-alcoholic fatty liver disease and hepatitis C infection

Non-alcoholic fatty liver disease (NAFLD) is now recognized as one of the most important causes of chronic liver disease in Western Countries, and is the hepatic manifestation of metabolic syndrome. The prevalence of NAFLD has increased with the global epidemic of obesity and type 2 diabetes mellitus. The pathophysiological hallmark of NAFLD is insulin resistance, associated with mediators of oxidative stress and inflammatory cytokines. Although simple steatosis by itself is generally benign, patients with histologically proven non-alcoholic steatohepatitis (NASH) can progress to cirrhosis. Hepatitis C (HCV) is another common cause of liver disease with some potential for progression to cirrhosis. Steatosis is present in almost 50% of patients infected by HCV. Hepatic steatosis in the setting of another liver disease (such as HCV) is associated liver disease progression. In particular, significant fibrosis is observed in patients with HCV whose liver biopsies show significant steatosis or superimposed NASH. This article reviews the host and viral factors potentially involved in the interaction between NAFLD and HCV. These factors include mediators of metabolic syndrome such as adipokines, inflammatory cytokines, factors associated with oxidative stress, lipid peroxidation products, as well as apoptosis and hepatic stellate cell activation with the resultant deposition of extracellular matrix. In addition to the mediators of metabolic syndrome (host factors), hepatic steatosis can be influenced by viral factors. The most important viral factor is HCV genotype 3, which has been independently associated with hepatic steatosis. Finally, superimposed NAFLD and visceral fat are associated with lower response rates to antiviral therapy in non-genotype 3 patients. Furthermore, viral clearance is associated with the resolution of hepatic steatosis in HCV genotype 3 but not other HCV genotypes. In these genotypes, hepatic steatosis and its impact on response to therapy are related to metabolic syndrome. Thus, the management of obesity and metabolic syndrome in patients with chronic hepatitis C may be important for reducing the risk of progression as well as improving the efficacy of antiviral therapy.     

Non-alcoholic fatty liver disease is associated with cardiovascular disease risk markers

Recognition of the link between non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) has boosted research in this area. The main objective of this paper is to review the literature on NAFLD in the context of CVD, focussing on underlying mechanisms and treatment. Besides excessive fatty acid influx, etiologic factors may include components of the metabolic syndrome, cytokines and mitochondrial dysfunction. NAFLD is associated with both hepatic and systemic insulin resistance. In the case of NAFLD, the liver overproduces several atherogenic factors, notably inflammatory cytokines, glucose, lipoproteins and coagulation factors, and factors increasing blood pressure. Intervention studies on diet and laparoscopic surgery revealed improvements of hepatic fat content and CVD risk profile. Pharmacological approaches with potential benefit have been developed as well, but effects are often confounded by weight change. NAFLD is associated with an increased CVD risk profile (and hepatic risk). In order to improve CVD risk profile, prevention and treatment of NAFLD seem advisable. However, well-designed intervention studies, randomized clinical trials and long-term follow-up studies are scarce.     

Non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that affects a high proportion of the world's population. Insulin resistance and oxidative stress play a critical role in the pathogenesis of NAFLD. Clinical, biochemical and imaging studies are of value in the diagnostic evaluation of patients with NAFLD, but liver biopsy remains the most sensitive and specific means of providing important diagnostic and prognostic information. Simple steatosis has the best prognosis within the spectrum of NAFLD, but NAFLD has the potential to progress to steatohepatitis, fibrosis and even cirrhosis. No effective medical therapy is currently available for all patients with NAFLD. In patients with diabetes mellitus and hyperlipidemia, appropriate metabolic control is always recommended, but rarely effective in resolving the liver disease. Weight reduction, when achieved and sustained, may improve the liver disease, although the results with weight loss have been inconsistent. Pharmacological therapy aimed at the underlying liver disease holds promise. Several medications with different mechanisms of action and potential benefit are currently being evaluated in clinical trials. Liver transplantation is a life-extending therapeutic alternative for patients with end-stage NAFLD, but NAFLD may recur after liver transplantation.     

Non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the Western world. It is closely associated with metabolic syndrome. The alarming epidemics of diabetes and obesity have fueled an increasing prevalence of NAFLD, particularly among these high-risk groups. Histologically, NAFLD encompasses a disease spectrum ranging from simple steatosis to non-alcoholic steatohepatitis (NASH), which is characterized by hepatocyte injury, inflammation, and variable degrees of fibrosis on liver biopsy. Non-alcoholic steatohepatitis can progress to cirrhosis in a fraction of patients. There is currently little understanding of risk factors for disease progression and the disease pathogenesis has not been fully defined. Liver biopsy remains the gold standard for diagnosis. Weight loss, dietary modification, and the treatment of underlying metabolic syndrome remain the mainstays of therapy once the diagnosis is established. There are no well-established pharmacological agents for treatment of NASH, although this is a subject of ongoing research.     

非酒精性脂肪肝、非酒精性脂肪肝合并代谢综合征患者血清脂联素水平及其与胰岛素抵抗程度的相关性分析

目的 研究非酒精性脂肪肝、非酒精性脂肪肝合并代谢综合征患者血清脂联素水平及其与胰岛素抵抗程度的相关性.方法 选取非酒精性脂肪肝106例,非酒精性脂肪肝合并代谢综合征58例,单纯肥胖32例,健康体检42例作为对照组.测定体重指数（BMI）和腰臀比（WHR）,检测空腹血糖（FBS）、丙氨酸氨基转移酶（ALT）、胆固醇（TC）、甘油三脂（TG）和高密度脂蛋自（HDL）等生化指标并行肝脏B超检查.放射免疫法测定空腹胰岛素（FINS）水平,计算胰岛素抵抗指数（HOMA）.同时酶联免疫法测定血清脂联素水平,并用相关及多元回归分析脂联素与各参数的相关性.结果 非酒精性脂肪肝组BMI、ALT、TC、TG、FBS、FINS和HOMA均较正常对照组高,HDL和脂联素水平较正常对照组低;非酒精性脂肪肝合并代谢综合征组胰岛素抵抗程度较非酒精性脂肪肝组更严重,脂联素水平更低.单纯肥胖组ALT、TC高于对照组,脂联素水平有下降趋势.非酒精性脂肪肝ALT异常组与ALT正常组比较,脂联素水平下降.结论 非酒精性脂肪肝存在不同程度胰岛素抵抗,脂联素水平降低;合并代谢综合征者胰岛素抵抗更为严重,脂联素水平更低;合并ALT异常时脂联素水平下降     

儿童非酒精性脂肪性肝病

非酒精性脂肪性肝病(NAFLD)是一种病变主体在肝小叶,以肝细胞弥漫性脂肪变性和脂肪蓄积为病理特征,无过量饮酒史的临床综合征。它包括单纯性脂肪肝(NAFL)及其演变的脂肪性肝炎(NASH)和脂肪性肝硬化3种类型。NAFLD的发病与肥胖有关。近20年来,肥胖症在儿童中发病迅速增加,NAFLD作为儿童慢性肝病的常见病逐渐引起人们的重视。     

Non-alcoholic fatty liver disease in children

Non-alcoholic fatty liver disease is increasingly prevalent in children, together with obesity. Transaminases, tests for insulin resistance, ultrasonography and MRI are variably used as surrogates markers of steatosis. Other liver diseases, such as Wilson disease, should be excluded. A liver biopsy is performed in selected cases: young children, familial history of severe disease, inconclusive tests for other pathologies, suspected advanced fibrosis, hypertransaminasemia despite weight loss and in clinical trials. Weight reduction, and changes in lifestyle, are the front-line treatment. Drug therapy is under evaluation.     

Non-alcoholic fatty liver disease in 2015

There is worldwide epidemic of non-alcoholic fatty liver disease(NAFLD). NAFLD is a clinical entity related to metabolic syndrome. Majority of the patients are obese but the disease can affect non-obese individuals as well. Metabolic factors and genetics play important roles in the pathogenesis of this disorder. The spectrum of disorders included in NAFLD are benign macrovesicular hepatic steatosis, non-alcoholic steatohepatitis, hepatic fibrosis, cirrhosis of liver and hepatocellular carcinoma. Although the disease remains asymptomatic most of the time, it can slowly progress to end stage liver disease. It will be the most common indication of liver transplantation in the future. It is diagnosed by abnormal liver chemistry, imaging studies and liver biopsy. As there are risks of potential complications during liver biopsy, many patients do not opt for liver biopsy. There are some noninvasive scoring systems to find out whether patients have advanced hepatic fibrosis. At the present time, there are limited treatment options which include lifestyle modification to loose weight, vitamin E and thioglitazones. Different therapeutic agents are being investigated for optimal management of this entity. There are some studies done on incretin based therapies in patients with NAFLD. Other potential agents will be silent information regulator protein Sirtuin and antifibrotic monoclonal antibody Simtuzumab against lysyl oxidase like molecule 2. But they are still in the investigational phase.     

Non-alcoholic fatty liver disease is not associated with a lower health perception

AIM: To examine the association between nonalcoholic fatty liver disease(NAFLD) and general health perception.METHODS: This cross sectional and prospective follow-up study was performed on a cohort of a subsample of the first Israeli national health and nutrition examination survey, with no secondary liver disease or history of alcohol abuse. On the first survey, in 2003-2004, 349 participants were included. In 2009-2010 participants from the baseline survey were invited to participate in a follow-up survey. On both baseline and follow-up surveys the data collected included: self-reported general health perception, physical activity habits, frequency of physician's visits, fatigue impact scale and abdominal ultrasound. Fatty liver was diagnosed by abdominal ultrasonography using standardized criteria and the ratio between the median brightness level of the liver and the right kidney was calculated to determine the Hepato-Renal Index.RESULTS: Out of 349 eligible participants in the first survey, 213 volunteers participated in the follow-up cohort and were included in the current analysis, NAFLD was diagnosed in 70/213(32.9%). The prevalence of "very good" self-reported health perception was lower among participants diagnosed with NAFLD compared to those without NAFLD. However, adjustment for BMI attenuated the association(OR = 0.73, 95%CI: 0.36-1.50, P = 0.392). Similar results were observed for the hepato-renal index; it was inversely associated with "very good" health perception but adjustment for BMI attenuated the association. In a full model of multivariate analysis, that included all potential predictors for health perception, NAFLD was not associated with the self-reported general health perception(OR = 0.86, 95%CI: 0.40-1.86, P = 0.704). The odds for "very good" self-reported general health perception(compared to "else") increased among men(OR = 2.42, 95%CI: 1.26-4.66, P = 0.008) and those with higher performance of leisure time physical activity(OR = 1.01, 95%CI: 1.00-1.01, P 0.001, per every minute/week) and decreased with increasing level of BMI(OR = 0.91, 95%CI: 0.84-0.99, P = 0.028, per every kg/m~2) and older age(OR = 0.96, 95%CI: 0.93-0.99, P = 0.033, per one year). Current smoking was not associated with health perception(OR = 1.31, 95%CI: 0.54-3.16, P = 0.552). Newly diagnosed(naive) and previously diagnosed(at the first survey, not naive) NAFLD patients did not differ in their self-health perception. The presence of NAFLD at the first survey as compared to normal liver did not predict health perception deterioration at the 7 years follow-up. In terms of health-services utilization, subjects diagnosed with NAFLD had a similar number of physician's visits(general physicians and specialty consultants) as in the normal liver group. Parameters in the fatigue impact scale were equivalent between the NAFLD and the normal liver groups.CONCLUSION: Fatty liver without clinically significant liver disease does not have independent impact on selfhealth perception.     

非酒精性脂肪肝和心血管疾病

非酒精性脂肪肝(NAFLD)是临床慢性肝脏疾病,包括单纯的肝细胞脂肪变、脂肪性肝炎(NASH)、肝脏纤维化甚至肝硬化等,是临床隐原性肝硬化最常见的病因。胰岛素抵抗(IR)和中央性肥胖是NAFLD的重要发病机制。同时由中央性肥胖、2型糖尿病、胰岛素抵抗、高血压及血脂异常等组成的代谢综合征(MS)是心血管疾病(CVD)的高危险因素。现在,越来越多的研究认为NAFLD是MS在肝脏系统的表现,NAFLD的出现可能不仅仅是CVD发生的标志,甚至是CVD的早期中间状态。     

Nonalcoholic fatty liver disease and HIV infection

Nonalcoholic fatty liver disease (NAFLD) is a clinicopathologic syndrome that includes a range of disorders associated with fatty liver from steatosis to cirrhosis and hepatocellular carcinoma, defined by the presence of liver fat accumulation exceeding 5% of hepatocytes in the absence of other causes of liver disease such as alcohol consumption, viral hepatitis, or any other specific etiology. Half the patients with human immunodeficiency virus (HIV) who undergo additional testing for unexplained liver test abnormalities may suffer from NAFLD, which is the hepatic manifestation of the metabolic syndrome. In HIV-infected patients, NAFLD can result from the HIV itself, highly active antiretroviral therapy (HAART), and/or lipodystrophy. Evaluation of the liver impact of NAFLD remains mainly based on liver biopsy, but numerous noninvasive procedures are under evaluation. In HIV/hepatitis C virus (HCV-) coinfected patients, steatosis seems more frequent and severe by comparison with HCV-monoinfected patients, and is associated with significant liver fibrosis, which may contribute to the more rapid progression of liver disease. First-line treatment of NAFLD is mainly based on the adequate management of the metabolic syndrome, including lifestyle changes. Specific therapeutic approaches are under investigation.     

非酒精性脂肪性肝病与甲状腺功能减退症

非酒精性脂肪性肝病与甲状腺功能异常的发病日渐增多,两者均与环境因素和生活方式有一定关系,但两者之间有否相关,是否与代谢异常有关仍不明确.非酒精性脂肪性肝病患者甲状腺激素水平低下,甲状腺功能减退症发生率增加.甲状腺激素可能通过影响脂代谢、氧化应激、线粒体功能、甲状腺激素受体表达等途径影响脂质在肝脏的沉积.因此,研究非酒精性脂肪性肝病与甲状腺功能异常的发病关系,为研发新型的非酒精性脂肪性肝病治疗药物提供了新的靶点.     

Non-alcoholic fatty liver disease is associated with high prevalence of gastro-oesophageal reflux symptoms

Background

Gastro-oesophageal reflux symptoms are usually reported by patients with obesity and metabolic syndrome. Aim of this study was to assess the prevalence and clinical characteristics of gastro-oesophageal reflux symptoms in subjects with non-alcoholic fatty liver disease.

Methods

Cross-sectional, case–control study of 185 consecutive patients with non-alcoholic fatty liver disease and an age- and sex-matched control group of 112 healthy volunteers. Participants were interviewed with the aid of a previously validated questionnaire to assess lifestyle and reflux symptoms in the 3 months preceding enrolment. Odds ratios were determined before and after adjustment for body mass index, increased waist circumference, physical activity, metabolic syndrome and proton pump inhibitors and/or antiacid medication.

Results

The prevalence of heartburn and/or regurgitation and of at least one of gastro-oesophageal reflux symptoms was significantly higher in the non-alcoholic fatty liver disease group. Non-alcoholic fatty liver disease subjects were associated to higher prevalence of heartburn (adjusted odds ratios: 2.17, 95% confidence intervals: 1.16–4.04), regurgitation (adjusted odds ratios: 2.61, 95% confidence intervals: 1.24–5.48) and belching (adjusted odds ratios: 2.01, 95% confidence intervals: 1.12–3.59) and had higher prevalence of at least one GER symptom (adjusted odds ratios: 3.34, 95% confidence intervals: 1.76–6.36).

Conclusion

Non-alcoholic fatty liver disease is associated with a higher prevalence of gastro-oesophageal reflux symptoms.     

Non-alcoholic fatty liver disease is associated with left ventricular diastolic dysfunction in essential hypertension

Background and aimInsulin resistance is recognized as the pathophysiological hallmark of non-alcoholic fatty liver disease (NAFLD). A relation between insulin sensitivity and left ventricular morphology and function has been reported in essential hypertension, where a high prevalence of NAFLD has been recently found. We investigated the inter-relationship between left ventricular morphology/function, metabolic parameters and NAFLD in 86 never-treated essential hypertensive patients subdivided in two subgroups according to the presence (n = 48) or absence (n = 38) of NAFLD at ultrasonography.Methods and resultsThe two groups were similar as to sex, age and blood pressure levels. No patient had diabetes mellitus, obesity, hyperlipidemia, or other risk factors for liver disease. Body mass index, waist circumference, triglycerides, glucose, insulin, homeostasis model of assessment index for insulin resistance (HOMA-IR), aspartate aminotransferase and alanine aminotransferase were higher and adiponectin levels were lower in patients with NAFLD than in patients without NAFLD, and were associated with NAFLD at univariate analysis. Patients with NAFLD had similar prevalence of left ventricular hypertrophy compared to patients without NAFLD, but a higher prevalence of diastolic dysfunction (62.5 vs 21.1%, P < 0.001), as defined by E/A ratio <1 and E-wave deceleration time >220 ms. Diastolic dysfunction (P = 0.040) and HOMA-IR (P = 0.012) remained independently associated with NAFLD at backward multivariate analysis.ConclusionsNon-alcoholic fatty liver disease was associated with insulin resistance and abnormalities of left ventricular diastolic function in a cohort of patients with essential hypertension, suggesting a concomitant increase of metabolic and cardiac risk in this condition.     

Non-alcoholic fatty liver disease and associated dietary and lifestyle risk factors

Nonalcoholic fatty liver disease (NAFLD) has emerged as the most common chronic liver disease worldwide with a reported prevalence ranging 20–30% depending on the studied populations. The high prevalence of NAFLD is probably due to the contemporary epidemics of obesity, unhealthy dietary pattern, and sedentary lifestyle. NAFLD patients are at increased risk of cardiovascular and liver related mortality. The cornerstone of any treatment regimen for patients with NAFLD is lifestyle modification focused on weight loss, exercise, and improving insulin sensitivity. The purpose of this review is to outline the effect of diet and lifestyle factors on developing NAFLD.     

Non-alcoholic fatty liver disease: an overview

Non-alcoholic fatty liver disease (NAFL) includes a spectrum of clinicopathological conditions with increasing prevalence in the developed world. Although steatosis alone seems to have a benign course, those patients with the diagnosis of non-alcoholic steatohepatitis (NASH) can have a progressive course. Additionally, there is now evolving, indirect evidence that some of the patients with cryptogenic cirrhosis may be the result of 'burned-out' NASH. Although NAFL and NASH are associated with insulin-resistance syndrome, some patients with NAFL may have no obvious risk factors. Despite preliminary data from a number of pilot studies, no established therapies can be offered to patients with NASH. Over the next few years, a number of exciting research projects dealing with the epidemiology as well as the pathogenesis of NAFL are expected to be completed. It is anticipated that, through a better understanding of NAFL, more effective treatment protocols can be developed targeting only those patients with NASH that are at the highest risk for progression to cirrhosis and liver failure.