Irisin in patients with nonalcoholic fatty liver disease

Objective

Irisin is a recently discovered myokine proposed to increase thermogenesis-related energy expenditure and improve metabolism. We aimed to comparatively evaluate serum irisin levels in patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD) vs. controls and study their association with disease severity.

Methods

Fifteen and 16 consecutively enrolled patients with biopsy-proven nonalcoholic simple steatosis (NAFL) and steatohepatitis (NASH), respectively, and 24 lean and 28 obese controls without NAFLD were recruited. Irisin, established adipokines and biochemical tests were measured.

Results

Serum irisin levels were statistically different in obese controls (33.7 ± 2.7 ng/mL; p < 0.001) and patients with NAFL (30.5 ± 1.5 ng/mL; p < 0.001) and NASH (35.8 ± 1.9 ng/mL; p = 0.001) compared with lean controls (47.7 ± 2.0 ng/mL), but were similar among patients with NAFL, NASH and obese controls. This difference remained significant after adjustment for body mass index (or waist circumference), gender, age, insulin resistance (assessed by HOMA-IR or QUICKI), exercise and time since blood collection. Serum leptin and adiponectin, but not irisin, levels were independently from BMI correlated with insulin resistance and cardiometabolic factors. Serum irisin tended to be higher in patients with (36.7 ± 2.4 ng/mL) than without (30.8 ± 1.2 ng/mL; p = 0.02) portal inflammation and independently associated with the latter; these data need to be confirmed by future studies.

Conclusions

Serum irisin levels differ between lean controls and obese controls or NAFLD patients. Despite similar circulating irisin levels between NAFL and NASH groups, irisin may be independently and positively associated with the presence of portal inflammation. Future clinical and mechanistic studies are needed to confirm and extend these data.     

Dyslipidemia in patients with nonalcoholic fatty liver disease

Patients with nonalcoholic fatty liver disease (NAFLD) often have dyslipidemia along with other features of metabolic syndrome such as obesity, diabetes mellitus, and hypertension. The dyslipidemia in NAFLD is characterized by increased serum triglycerides, increased small, dense low-density lipoprotein (LDL nontype A) particles, and low high-density lipoprotein (HDL) cholesterol. The pathogenesis of dyslipidemia in NAFLD is not well understood, but it is likely related to hepatic overproduction of the very low-density lipoprotein particles and dysregulated clearance of lipoproteins from the circulation. There is unequivocal evidence that cardiovascular disease is the most common cause of mortality in patients with NAFLD. Aggressive treatment of dyslipidemia plays a critical role in the overall management of patients with NAFLD. Statins are the first-line agents to treat high cholesterol and their dosage should be adjusted based on achieving therapeutic targets and tolerability. Although all statins appear to be effective in improving cholesterol levels in patients with NAFLD, there is more experience with atorvastatin in patients with NAFLD; furthermore, it is the only statin to date to show a reduced cardiovascular morbidity in patients with NAFLD. The risk for serious liver injury from statins is quite rare and patients with NAFLD are not at increased risk for statin hepatotoxicity. Omega-3 fatty acids are perhaps the first choice to treat hypertriglyceridemia because of their safety, tolerability, and efficacy in improving serum triglycerides, as well as their potential to improve liver disease.     

非酒精性脂肪性肝病与高尿酸血症

<正>非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)是临床最常见的慢性肝病之一,我国成年人NAFLD患病率超过15%,并且呈现不断上升趋势[1]。近年来,越来越多的研究报道,高尿酸血症与NAFLD密切相关。临床研究发现,NAFLD患者常合并高尿酸血症,并且高尿酸血症显著增加NAFLD的发病风险。动物实验结果表明,高尿酸能引发NAFLD发生,降尿酸干预可有效减轻NAFLD     

非酒精性脂肪性肝病治疗研究进展

非酒精性脂肪性肝病是全球性的公共卫生问题。调整生活方式及保持健康心理状态是治疗非酒精性脂肪性肝病的基础。本文通过对其发病机理研究的梳理,重点介绍了近年来国内外关于非酒精性脂肪性肝病药物治疗的进展,包括氧化应激、炎症反应、脂质代谢、纤维形成和细胞凋亡等不同阶段靶向治疗药物应用的安全性和有效性。     

非酒精性脂肪性肝病患者动脉僵硬度的变化及其影响因素分析*

目的 研究不同年龄段非酒精性脂肪性肝病（NAFLD）患者外周动脉僵硬度的变化,探讨影响动脉僵硬度增高的相关危险因素。方法 根据超声检查是否存在脂肪肝将2382例健康体检者分为NAFLD组和无NAFLD组,分析各年龄段两组间肱踝脉搏波传导速度（baPWV）的变化特点。以baPWV≥1400 cm/s为动脉僵硬度增高,采用Logistic回归分析影响动脉僵硬度增高的危险因素。结果 在2382例体检者中,发现NAFLD患者935例（39.3%）,在1595例男性中,检出NAFLD 患者726例（45.5%）,在787例女性中,检出NAFLD患者209例（26.6%,P<0.001）;在616例20~39岁、1463例40~59岁和303例>60岁人群中,分别发现NAFLD188例（30.5%）、623例（42.6%）和124例（40.9%）; 20～39岁年龄段NAFLD组baPWV水平为（1340.0±180.7） cm/s,显著高于无NAFLD组［（1203.9±155.2） cm/s,P<0.001］,40～59岁年龄段NAFLD组baPWV水平为（1437.1±232.6） cm/s,显著高于无NAFLD组［（1355.8±217.9） cm/s,P<0.001］,大于60岁年龄段NAFLD组baPWV水平为（1885.8±404.0） cm/s,与无NAFLD组的baPWV水平［（1830.2±430.6） cm/s］无统计学差别（P>0.05）;在1643例血压正常者,二分类Logistic回归分析发现,年龄、性别、NAFLD、血清总胆固醇为baPWV升高的独立危险因素。结论 NAFLD患者较无NAFLD人群动脉僵硬度增高,以青中年NAFLD患者增高更为明显。NAFLD为动脉僵硬度增高的独立危险因素。     

非酒精性脂肪性肝病的疗效评价

目前,对于非酒精性脂肪性肝病有中西医两种治疗方法,但这两种治疗方法的疗效评价体系均不够完善.系统回顾目前的中医疗效评价,可以发现主要存在以下问题:第一,对于现有的评价体系未能积极完整地实施,过于强调客观指标,忽略了主观指标,并且人为地舍弃部分样本;第二,对照药物选择比较随意.可比性较差;第三,中医临床对照研究中,治疗组和对照组证型不统一,可比性较差.为进一步完善疗效评价,建议严格执行现有的疗效评价方案,并研制具有中医特色的非酒精性脂肪性肝病的PRO量表.     

非酒精性脂肪性肝病患者人体脂肪成分指标的变化

目的 调查非酒精性脂肪性肝病（NAFLD）患者人体成分及其变化情况,为NAFLD的早期预防和治疗提供科学依据。 方法 使用百利达MC180人体成分分析仪对148例NAFLD患者进行人体成分分析,获得体质量、身高、体质指数（BMI）、肌肉量、脂肪量、骨量、脂肪率及其分布、内脏脂肪等级等指标。 结果 本组NAFLD患者高体脂肪含量发生率为51.4%,其中,18~39岁患者高体脂肪含量发生率（86.3%）显著高于中老年患者（分别为39.3%和24.4%）;男性患者肌肉量、骨量、内脏脂肪等级均高于女性,女性脂肪量和体脂肪率高于男性（P<0.01）;男女性患者随年龄增加体脂肪率和躯体脂肪率降低（P<0.01）,男性患者上肢脂肪率和女性患者上、下肢脂肪率均随年龄增加而降低（P<0.01）;本组NAFLD患者骨量低于标准发生率,为49.3%,NASH发生率为20.3%。 结论 NAFLD患者人体成分的变化主要表现在体脂肪率增加和骨量降低,并且年轻患者高体脂肪含量发生率更高。     

Role of leisure-time physical activity in nonalcoholic fatty liver disease: a population-based study

Physical activity (PA) is commonly recommended for nonalchoholic fatty liver disease (NAFLD) patients. However, there is limited evidence on the independent role of PA in NAFLD. The aim of this study was to examine the association between PA and NAFLD. We conducted a cross-sectional study of a subsample (n = 375) of the Israeli National Health and Nutrition Survey. Exclusion criteria were any known etiology for liver disease. Participants underwent an abdominal ultrasound examination; biochemical tests, including leptin, adiponectin, and resistin; and the noninvasive biomarker SteatoTest and anthropometric evaluations. A semiquantitative food frequency questionnaire and a detailed PA questionnaire were administered. Three hundred forty-nine patients (52.7% men, 30.9% primary NAFLD) were included. The NAFLD group engaged in less aerobic, resistance, or other kinds of PA (P 相似文献   

Fractionation of gamma-glutamyltransferase in patients with nonalcoholic fatty liver disease and alcoholic liver disease

AIM To assess how serum gamma-glutamyltransferase(GGT) fractions vary in patients with alcoholic liver disease(ALD) and non-alcoholic fatty liver disease(NAFLD). METHODS Serum samples were obtained from 14 patients with biopsy-proven alcoholic liver diseases and 9 patients with biopsy proven non-alcoholic fatty liver disease. In addition to these biopsy-proven cases, 16 obese(body mass index 25) patients without any history of alcohol consumption but with a fatty liver on ultrasound examination and with elevated GGT were included for an additional analysis. Serum GGT fractionation was conducted by high-performance gel filtration liquid chromatography and was separated into the four fractions, big-GGT, medium-GGT, small-GGT(s-GGT), and free-GGT(f-GGT).RESULTS The results were expressed as a ratio of each fraction including the total GGT(t-GGT). The s-GGT/t-GGT ratioswere lowest for the control group and highest for the ALD group. The differences between the control and NAFLD groups and also between the NAFLD and ALD groups were statistically significant. In contrast, the f-GGT/t-GGT ratios were highest in the control group and lowest in the ALD group, with the differences being statistically significant. As a result, the s-GGT/f-GGT ratios were markedly increased in the NAFLD group as compared with the control group. The increase of the s-GGT/t-GGT ratios, the decrease of the f-GGT/t-GGT ratios, and the increase of s-GGT/F-GGT ratios as compared with the control group subjects were also found in obese patients with clinically diagnosed fatty change of the liver.CONCLUSION Serum GGT fractionation by high-performance gel filtration liquid chromatography is potentially useful for the differential diagnosis of ALD and NAFLD.     

Serum homocysteine levels in patients with nonalcoholic fatty liver disease

Background and rational for the study. Nonalcoholic fatty liver disease (NAFLD) is regarded as the hepatic component of insulin resistance (IR) syndrome, but data on serum homocysteine (HCY) are limited. The aim of the study was the evaluation of serum HCY levels in patients with NAFLD. Material and methods. Thirty-one patients (54 ± 11 years, 8 males) with biopsy-proven NAFLD, 15 with simple nonalcoholic fatty liver (NAFL) and 16 with nonalcoholic steatohepatitis (NASH), and 22 healthy controls (52 ± 9 years, 5 males) matched for gender, age and body mass index (BMI), were recruited. Blood samples for HCY, folate, vitamin B12, insulin and standard biochemical tests were obtained after overnight fasting. Homeostatic model of assessment-insulin resistance (HOMA-IR) was calculated. Results. There was no difference in mean serum HCY levels between controls and NAFLD patients (12.6 ± 4.6 vs. 13.5 ± 2.6 mmol/L, respectively; p = 0.432). Serum folate and vitamin B12 were also similar between the study groups. Mean age, BMI, serum folate and vitamin B12 did not differ between NAFL and NASH patients. However, when compared with NAFL patients, NASH patients had lower mean serum HCY levels (12.3 ± 2.5 vs. 14.7 ± 2.1 mmol/L; p = 0.006). HCY was lower by increasing the grading of fibrosis (p = 0.005), portal inflammation (p = 0.029) and steatosis location (p = 0.021). In logistic regression analysis, HCY independently predicted NASH (p = 0.045) after adjustment for gender, age, BMI, AST, glucose and HOMA-IR. Conclusion. Our data suggest that serum HCY levels are lower in NASH compared with NAFL patients and can independently predict NASH. Serum HCY might represent another non-invasive marker for the assessment of NAFLD.     

非酒精性脂肪性肝病患者血脂变化的流行病学调查

目的探讨非酒精性脂肪性肝病(NAFLD)患者血脂变化及其与脂肪肝程度的关系。方法回顾性分析我院门诊就诊的NAFLD患者638例,检测肝功能、血脂、血糖、胰岛素抵抗指数(HOMA-IR)及肝脏CT表现。结果 NAFLD患者TG为2.14±1.62mmol/L,TC为5.19±1.02mmol/L,LDL-C为2.71±0.74mmol/L,HDL-C为1.18±0.26mmol/L,APOA1为1.15±0.26mg/L,APOB为0.96±0.25mg/L,LP(α)为252.6±192.7mg/L,non-HDL-C为4.01±0.82 mmol/L,FBG为5.94±1.04 mmol/L,和HOMA-IR为3.54±2.52;血脂以TG升高为主,FBG、HOMA-IR、TC、APO-B、NON-HDL-C均随脂肪肝程度加重而升高(P<0.05);不同程度脂肪肝患者HDL-C、LDL-C、APO-A1和TG未发现明显统计学差异(P>0.05);患者ALT与脂肪肝程度、BMI和HOMA-IR呈正相关,而与空腹血糖(FBG)和血脂无明显统计学相关(P>0.05)。结论 NAFLD患者血脂异常以TG升高为主,NAFLD患者随脂肪肝程度的加重,TC、APO-B、NON-HDL-C升高。     

非酒精性脂肪性肝病相关慢性肾病研究进展

非酒精性脂肪性肝病是与胰岛素抵抗和遗传易感性密切相关的代谢应激性肝损伤。该病已经成为全球性的公共卫生问题之一。近几年来,有研究显示非酒精性脂肪性肝病可能与慢性肾病越来越高的患病率有关。本文将重点阐述这两个疾病的相互关系以及相关发生机制,比如胰岛素抵抗、炎症、氧化应激、高凝状态、胎球蛋白-A和脂联素等在该病发病中的作用,为更全面管理非酒精性脂肪性肝病患者和慢性肾病患者提供有用的建议。     

Histopathological differences utilizing the nonalcoholic fatty liver disease activity score criteria in diabetic (type 2 diabetes mellitus) and non-diabetic patients with nonalcoholic fatty liver disease

AIM: To study clinical and histopathological features of nonalcoholic fatty liver disease(NAFLD) in patients with and without type 2 diabetes mellitus(T2DM) using updated nonalcoholic steatohepatitis clinical research network(NASH-CRN) grading system.METHODS: We retrospectively analyzed data of 235 patients with biopsy proven NAFLD with and without T2 DM.This database was utilized in the previously published study comparing ethnicity outcomes in NAFLD by the same corresponding author.The pathology database from University of Chicago was utilized for enrolling consecutive patients who met the criteria for NAFLD and their detailed clinical and histopathology findings were obtained for comparison.The relevant clinical profile of patients was collected from the Electronic Medical Records around the time of liver biopsy and the histology was read by a single well-trained histopathologist.The updated criteria for type 2 diabetes have been utilized for analysis.Background data of patients with NASH and NAFLD has been included.The mean differences were compared using χ2 and t-test along with regression analysis to evaluate the predictors of NASH and advanced fibrosis.RESULTS: Patients with NAFLD and T2 DM were significantly older(49.9 vs 43.0,P 0.01),predominantly female(71.4 vs 56.3,P 0.02),had higher rate of metabolic syndrome(88.7 vs 36.4,P 0.01),had significantly higher aspartate transaminase(AST)/alanine transaminase(ALT) ratio(0.94 vs 0.78,P 0.01) and Fib-4 index(1.65 vs 1.06,P 0.01) as markers of NASH,showed higher mean NAFLD activity score(3.5 vs 3.0,P = 0.03) and higher mean fibrosis score(1.2 vs 0.52,P 0.01) compared to patients with NAFLD without T2 DM.Furthermore,advanced fibrosis(32.5 vs 12.0,P 0.01) and ballooning(27.3 vs 13.3,P 0.01) was significantly higher among patients with NAFLD and T2 DM compared to patients with NAFLD without T2 DM.On multivariate analysis,T2 DM was independently associated with NASH(OR = 3.27,95%CI: 1.43-7.50,P 0.01) and advanced fibrosis(OR = 3.45,95%CI: 1.53-7.77,P 0.01) in all patients with NAFLD.There was a higher rate of T2DM(38.1 vs 19.4,P 0.01) and cirrhosis(8.3 vs 0.0,P = 0.01) along with significantly higher mean Bilirubin(0.71 vs 0.56,P = 0.01) and AST(54.2 vs 38.3,P 0.01) and ALT(78.7 vs 57.0,P = 0.01) level among patients with NASH when compared to patients with steatosis alone.The mean platelet count(247 vs 283,P 0.01) and high-density lipoprotein cholesterol level(42.7 vs 48.1,P = 0.01) was lower among patients with NASH compared to patients with steatosis.CONCLUSION: Patients with NAFLD and T2 DM tend to have more advanced stages of NAFLD,particularly advanced fibrosis and higher rate of ballooning than patients with NAFLD without T2 DM.     

非酒精性脂肪性肝病患者瘦素与肝纤维化的关系

目的:研究非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)患者血清瘦素水平与肝纤维化指标的相关性,来探讨瘦素在NAFLD发展进程中的作用.方法:应用放射免疫法(RIA)测定33例NAFLD患者及30例对照组的瘦素、透明质酸(HA)、层粘蛋白(LN)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(Ⅳ-C),并测定空腹血糖(FBG)、总胆固醇(TC)、三酰甘油(TG)、空腹胰岛素(FINS)、体质量指数检测(BMI)等临床指标.结果:NAFLD患者的瘦素、BMI、空腹胰岛素及胰岛素抵抗指数(HOMA IR)分别为11.07 μg/L±3.40 μg/L、27.33±2.98、14.19 mU/L±2.65 mU/L、3.48±0.65,显著高于对照组(P＜0.05);血清PCⅢ、Ⅳ-C、LN、HA在轻度NAFLD患者分别为68.17 μg/L±19.31 μg/L、39.06 μg/L±13.84 μg/L、62.51 μg/L±21.37 μg/L、44.52 μg/L±14.73 μg/L,与对照组比较无显著性差异(P＞0.05),在中、重度NAFLD患者分别为164.62 μg/L±18.47 μg/L、83.32 μg/L±24.73μg/L、152.22 μg/L±20.74 μg/L、212.51 μg/L±19.62 μg/L,明显高于对照组(P＜0.05),以HA最为显著(P＜0.01);轻度NAFLD患者,其血清瘦素与肝纤维化指标无相关关系(P＞0.05);中、重度NAFLD患者血清瘦素水平与肝纤维化指标有相关关系(P＜0.05).结论:瘦素与NAFLD患者肝纤维化进程密切相关.     

Metabolic aspects of adult patients with nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease(NAFLD) is a major cause of chronic liver disease and it encompasses a spectrum from simple steatosis to steatohepatitis, fibrosis, or cirrhosis. The mechanisms involved in the occurrence of NAFLD and its progression are probably due to a metabolic profile expressed within the context of a genetic predisposition and is associated with a higher energy intake. The metabolic syndrome(MS) is a cluster of metabolic alterations associated with an increased risk for the development of cardiovascular diseases and diabetes. NAFLD patients have more than one feature of the MS, and now they are considered the hepatic components of the MS. Several scientific advances in understanding the association between NAFLD and MS have identified insulin resistance(IR) as the key aspect in the pathophysiology of both diseases. In the multi parallel hits theory of NAFLD pathogenesis, IR was described to be central in the predisposition of hepatocytes to be susceptible to other multiple pathogenetic factors. The recent knowledge gained from these advances can be applied clinically in the prevention and management of NAFLD and its associated metabolic changes. The present review analyses the current literature and highlights the new evidence on the metabolic aspects in the adult patients with NAFLD.