Association between urine retinol‐binding protein levels and nonalcoholic fatty liver disease: A cross‐sectional study in Chinese population

Objective

The prevalence of nonalcoholic fatty liver disease (NAFLD) has been rapidly increased, becoming a public health problem worldwide. Our objective was to investigate the association between urine retinol‐binding protein (RBP) and NAFLD in a Chinese population and develop a multivariate logistic regression model for NAFLD prediction.

Methods

A total of 317 NAFLD patients and 391 healthy controls were enrolled in this cross‐sectional study based on inclusion and exclusion criteria, from whom fasting urine and blood were collected for further study. Urine RBP level and other parameters were measured and compared between NAFLD subjects and controls.

Results

Urine RBP levels (expressed by RBP/creatinine ratio) in NAFLD patients were significantly higher than controls (median 133.1 mg/g vs 110.7 mg/g; P < .001). Urine RBP/creatinine ratio was verified as an independent factor for NAFLD prediction after adjustment in multivariate logistic regression. The area under curve (AUC) of receiver operating characteristic (ROC) was 0.889 with the 95% confidence interval from 0.867 to 0.912.With a cutoff point of 0.215, the sensitivity and specificity of urine RBP/creatinine ratio in NAFLD prediction were 81.1% and 84.5%, respectively.

Conclusion

Our results demonstrated that urine RBP/creatinine ratio was an independent risk factor for NAFLD while the predictive model for NAFLD diagnosis is noninvasive with high sensitivity and specificity.

     

Progress and challenges in the prevention and control of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the most common liver disease worldwide. Individuals with NAFLD have a high frequency of developing progressive liver disease and metabolism-related comorbidities, which result from of a lack of awareness and poor surveillance of the disease and a paucity of approved and effective therapies. Managing the complications of NAFLD has already begun to place a tremendous burden on health-care systems. Although efforts to identify effective therapies are underway, the lack of validated preclinical NAFLD models that represent the biology and outcomes of human disease remains a major barrier. This review summarizes the characteristics and prevalence of the disease and the status of our understanding of its mechanisms and potential therapeutic targets.     

MTHFR基因677C/T和血清同型半胱氨酸水平与非酒精性脂肪性肝病的相关性

目的 探讨MTHFR基因677C/T和血清同型半胱氨酸(Hcy)水平与非酒精性脂肪性肝病(NAFLD)的相关性.方法 纳入249例成人住院患者,参照NAFLD亚洲诊断标准将其分为NAFLD组(131例)和对照组(118例).采集两组患者的基本资料并检测Hcy水平和MTHFR基因分型,行Hardy-Weinberg遗传平...     

Lipopolysaccharides accelerate hepatic steatosis in the development of nonalcoholic fatty liver disease in Zucker rats

Nonalcoholic fatty liver disease (NAFLD) can develop into end-stage disease that includes cryptogenic cirrhosis and hepatocellular carcinoma. Bacterial endotoxin, for example lipopolysaccharide (LPS), plays an important role in the pathogenesis of NAFLD. The aim of this study was to assess the role of LPS in the development of NAFLD. Twenty-one male Zucker (fa/fa) rats were divided into three groups: rats fed for twelve weeks on a diet rich in disaccharide (D12 group), rats similarly managed but treated with LPS (LPS group), and those on the same diet for 24 weeks (D24 group). Histological examination demonstrated that this protocol induced hepatic steatosis in the LPS and D24 groups. Significant, marked accumulation of lipid droplets was observed in the LPS group, compared with the D24 group. Rats from the LPS group showed a decrease in plasma adiponectin levels, an increase in plasma leptin levels, and greater expression of FAS and SREBP-1c mRNA in the liver, compared with rats from the D24 group. These finding coincided with histological findings. We therefore suggest that LPS may accelerate the progression of hepatic steatosis.     

老年代谢综合征与非酒精性脂肪肝患者载脂蛋白E基因多态性检测的意义

目的探讨老年代谢综合征(MS)与非酒精性脂肪肝(NAFL)的载脂蛋白E(apo E)基因多态性之间的关系及意义。方法本研究以60岁以上农村老年健康体检者筛检出的NAFL 126例、NAFL MS 105例、非脂肪肝125例及体检正常老年者95名为研究对象,其血液应用特异引物扩增人DNA apo E基因265 bp片段和特异探针杂交后,通过分析熔解曲线检测基因突变点及多态性。酶联免疫吸附试验(ELISA)检测apo E、apo E4基因浓度,并进行血脂、血糖、尿素、酶类、体质指数和血压分析。结果NAFL组和NAFL MS组以杂合子E2/3、E3/4基因型频率最高,分布频率分别为E2/3(36.5%、28.1%)、E3/4(27.2%、32.6%)、E3/3(32.3%、34.0%)、E2/4(2.4%、1.5%)、E4/4(0.8%、3.8%)、E2/2(0.8%、0.0%);NAFL MS组E4/4频率显著高于对照组,apoE基因总浓度明显升高(P<0.05),E2/3、E3/4 2组血脂等生化指标和体质指数及血压均有不同程度增高,差异有显著性(P<0.05)。结论apo E基因多态性与老年NAFL和MS存在相关性,携带E3/4、E2/3型或E4/4型的个体存在,提示在决定个体老年MS合并NAFL遗传易感性方面有重要作用,apo E基因112位和158位的氨基酸残基发生相应的变化可引起不同程度的脂质代谢障碍。     

Association of serum creatinine-to-cystatin C ratio with skeletal muscle mass and strength in nonalcoholic fatty liver disease in the Iwaki Health Promotion Project

We evaluated the feasibility of using serum creatinine-to-cystatin C ratio in the assessments of muscle mass and strength in nonalcoholic fatty liver disease. In a community-based cross-sectional study, skeletal muscle mass and handgrip strength were assessed in 641 Japanese adults. Low skeletal muscle mass index and low handgrip strength were defined as indicated in the sarcopenia diagnostic criteria of the Japan Society of Hepatology. Nonalcoholic fatty liver disease was defined as fatty liver on ultrasonography in the absence of other causes of steatosis. The creatinine-to-cystatin C ratio was useful for identifying the participants with low skeletal muscle mass index, with an area under the receiver-operating characteristic curve of 0.84 [95% confidence interval (CI), 0.77–0.91] in men and 0.72 in women (95% CI, 0.65–0.78), and those with low handgrip strength, with an area under the receiver-operating characteristic curve of 0.96 (95% CI, 0.93–0.99) in men and 0.79 (95% CI, 0.66–0.92) in women. Moreover, the creatinine-to-cystatin C ratio correlated with skeletal muscle mass index (r = 0.511, p<0.001) and handgrip strength (r = 0.657, p<0.001), whereas it did not correlate with exacerbation of hepatic steatosis. In this study, creatinine-to-cystatin C ratio correlated with muscle mass and strength in nonalcoholic fatty liver disease regardless of hepatic steatosis.     

非酒精性脂肪肝治疗进展

近年来随着生活水平的改善和生活方式的改变，非酒精性脂肪肝的发病率不断升高，其病因和发病机制尚未完全明了，针对脂肪肝的治疗尚缺乏有效的药物。本文就近年来对非酒精性脂肪肝的治疗进展作一综述。     

中国人群载脂蛋白E基因多态性与他汀类药物疗效关系的Meta分析

目的：评价中国人群载脂蛋白 E(APOE)基因多态性对他汀类药物降脂疗效的影响。方法在数据库中检索,获取 APOE 基因多态性与他汀类药物疗效关系的文献,筛选并对纳入文献进行质量评分和数据提取,使用RevMan 5.3软件进行 Meta 分析。结果ε2等位基因携带者低密度脂蛋白胆固醇(LDL-C)降低水平显著大于ε3ε3基因型(高脂血症组 P <0.05;阿托伐他汀组 P <0.01)和ε4等位基因(冠心病组 P =0.01;阿托伐他汀组 P =0.01)。ε2等位基因总胆固醇(TC)降低水平显著大于ε3ε3基因型(高脂血症组 P <0.01)和ε4等位基因(高脂血症组 P <0.01;冠心病组 P =0.02;阿托伐他汀组 P <0.01)。ε3ε3基因型甘油三酯(TG)降低水平显著大于ε4等位基因(总体 P <0.01;高脂血症组 P =0.03;辛伐他汀组 P =0.03)。ε2等位基因高密度脂蛋白胆固醇(HDL-C)升高水平显著大于ε3ε3基因型(高脂血症组 P =0.02)。结论 APOE 基因多态性与他汀类药物疗效相关,ε2等位基因携带者具有更好的降脂效果。     

血浆致动脉粥样硬化指数与非酒精性脂肪性肝病的相关性

目的 探讨血浆致动脉粥样硬化指数(AIP)与非酒精性脂肪性肝病(NAFLD)的关系.方法 选取四川大学望江医院健康体检中心2020年5月-2021年5月行彩色超声初次诊断为NAFLD且未经过药物治疗的160例体检者作为NAFLD组,随机选取160例同期年龄及性别匹配的健康体检者作为对照组;记录两组的年龄、身高、体重、血...     

2型糖尿病合并非酒精性脂肪性肝病肝纤维化与骨密度的相关性

目的:探讨2型糖尿病(type 2 diabetes mellitus,T2DM)合并非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)肝纤维化与骨密度的关系。方法:筛选T2DM患者539例,依据腹部超声分为T2DM组(n=234)、T2DM+NAFLD组(n=305),再依据非酒精性脂肪肝肝纤维化评分(non-alcoholic fatty liver disease fibrosis score,NAFLDFS)分为<-1.455排除纤维化亚组、-1.455~0.676可疑纤维化亚组、>0.676诊断纤维化亚组,行骨密度检查并测定空腹血糖(fasting blood glucose,FBG)、空腹C肽(fasting C-peptide,F-CP)、空腹胰岛素(fasting insulin,FINS)、糖化血红蛋白(HbA1c)、肝功能及血脂等血清学指标。结果:与T2DM组相比,T2DM+NAFLD组股骨颈、Ward’s三角、大粗隆、股骨干及全部股骨的骨密度及T值下降(P<0.05)。与-1.455~0.676亚组及<-1.455亚组相比,>0.676亚组股骨颈、Ward’s三角的骨密度及T值下降(P<0.05)。T2DM组和T2DM+NAFLD组骨量异常(骨量减少和骨质疏松)发生率存在差异(48.29%vs 65.90%,P<0.01);<-1.455亚组,-1.455~0.676亚组,>0.676亚组骨量异常发生率存在差异(48.39%vs 67.98%vs 82.5%,两两比较均P<0.01)。相关性分析示:NAFLDFS与股骨颈、Ward’s三角的骨密度及T值呈负相关(P<0.05)。Logistic回归分析示:在控制年龄、性别、BMI、病程、FBG、ALT、HDLC、HbA1C及载脂蛋白B(APOB)后,NAFLDFS评分是骨量减少的独立危险因素。-1.455~0.676亚组相对于<-1.455亚组骨量减少的风险增加(OR=2.235,95%CI 1.040~4.803,P<0.05);>0.676亚组相对于<-1.455亚组骨量减少的风险增加(OR=4.463,95%CI 1.221~16.308,P<0.05)。结论:T2DM合并NAFLD肝纤维化患者骨密度减低,两者具有相关性,进展性肝纤维化是骨量减少的危险因素。     

载脂蛋白E基因多态性与高血压胰岛素抵抗的相关性研究

目的:探讨载脂蛋白E基因多态性与原发性高血压胰岛素抵抗及脂代谢异常的相关性。方法:高血压患者142例,分为胰岛素抵抗组59例和非胰岛素抵抗组83例,采集静脉血,提取DNA,采用基因测序法检测载脂蛋白E基因多态性。结果:高血压胰岛素抵抗患者中E4等位基因频率要明显高于非胰岛素抵抗患者,E2等位基因频率低于非胰岛素抵抗患者。携带E4等位基因者(E3/4+E4/4)空腹血糖、空腹胰岛素、HOMA胰岛素抵抗指数均高于携带E2基因者(E2/2+E2/3),携带E4等位基因总胆固醇、低密度脂蛋白、三酰甘油均明显高于携带E2基因者,而高密度脂蛋白明显低于携带E2基因者。结论:载脂蛋白E基因E4等位基因影响高血压患者胰岛素抵抗程度及脂代谢水平。     

健康体检人群营养素摄入水平及其与非酒精性脂肪肝关系的研究

目的了解健康体检人群膳食营养素的摄入情况及其与主要体检结果,尤其是与非酒精性脂肪肝（NAFLD）的关联性。方法随机抽取并筛选了山东省青岛疗养院禾联健检中心查体的450名人员,收集其体检报告,并对个人采用24h膳食回顾法对其进行膳食调查。结果被调查人群平均每人日能量摄入量为2984.96cal（1cal=4.2J,男性：3282.66cal,女性：2304.80cal）,蛋白质126.17g,钙603.14mg,铁37.64mg,占推荐膳食摄入量（RNI）的124.37%,168.22%,79.30%,284.67%。维生素摄入中视黄醇、硫胺素、核黄素和抗坏血酸低于RNI标准。NAFLD的患病率32.2%,男女之间差异有高度统计学意义（χ2=35.405,P〈0.01）,不同年龄段之间差异有高度统计学意义（χ2=43.352,P〈0.01）,按性别、年龄段配对分组经单因素和多因素非条件Logistic回归分析,结果显示在社会经济类因素中体育锻炼（OR=0.7664）和饮酒史（OR=0.8487）与NAFLD有显著关联。以上因素为协变量进行协方差分析显示NAFLD患病组每人日能量、蛋白质、脂肪的摄入量高于正常对照组（F=22.211、36.868、32.029,P〈0.01）,膳食纤维摄入量低于正常对照组（F=10.428,P〈0.01）。结论被调查人群营养素平均摄入量基本能满足机体需要,但膳食结构仍不够合理,部分营养素摄入存在过量或缺乏的状况。营养相关性疾病的患病率有逐年升高的趋势,高能量、高脂肪、高蛋白、低纤维素摄入以及缺乏体育锻炼、饮酒等不良饮食生活习惯可能是NAFLD患病的危险因素。因此建立合理的膳食结构、倡导健康的生活方式,是预防和控制NAFLD发生发展的重要措施。     

载脂蛋白E基因多态性与中国人2型糖尿病肾脏并发症的相关性研究

目的 研究ApoE基因多态性与中国人2型糖尿病及其肾脏并发症（DN）的相关性。方法 以ApoE基因为候选基因,应用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析法检测78例糖尿病患者和49例健康体检者的ApoE基因型,其中合并肾脏并发症40例,无肾脏病变（DRD）38例。结果 DN组ApoE的ε2等位基因频率明显高于DRD组和正常对照组（P〈0.05）。DM患者的年龄、病程、高血压、GHB及ApoEε2等位基因频率与DN关系的Logistic回归分析：病程和ApoE的ε2等位基因与DN的发生密切相关（P〈0.05）,病程对DN的OR值为1.1494,而ApoE的ε2等位基因对DN的OR值为7.6514。结论 ApoE的ε2等位基因是2型DM并发DN的遗传易感因子。     

Gamma‐Glutamyl Transpeptidase‐to‐Platelet ratio predicts liver fibrosis in patients with concomitant chronic hepatitis B and nonalcoholic fatty liver disease

ObjectivesThe aim of this study was to compare the correlation of gamma‐glutamyl transpeptidase‐to‐platelet ratio (GPR), aspartate aminotransferase‐to‐platelet ratio index (APRI), fibrosis index‐4 (FIB‐4), and liver stiffness measurement (LSM) in the diagnosis of liver fibrosis, and perform a diagnostic value of GPR for predicting fibrosis in CHB patients with NAFLD.MethodsA retrospective study was conducted on CHB patients concurrent with NAFLD between September 2019 and December 2020. They were divided into control group (LSM ≤ 9.7 kpa) and fibrosis group (LSM ≥ 9.8 kpa). Demographic data were collected; ALT, AST, and PLT were also detected. LSM was measured by transient elastography (TE). The GPR, APRI, and FIB‐4 were calculated. The correlation between GPR, APRI, FIB‐4, and LSM was compared. The accuracy of predicting liver fibrosis using GPR, APRI, and FIB‐4 was assessed.ResultsEighty‐five CHB patients with NAFLD were enrolled. Multivariate analysis showed that age (p = 0.005), GGT (p = 0.001), and PLT (p = 0.013) were the independent risk factors for LSM. The GPR (p = 0.008), APRI (p = 0.001), and FIB‐4 (p = 0.001) values in fibrosis group were higher than control group. Pearson linear correlation was used to analyze the correlations between LSM and GPR, APRI, and FIB‐4. LSM was correlated with GPR, APRI, and FIB‐4. The AUCs of GPR, APRI, and FIB4 were 0.805, 0.766, and 0.826 in assessing liver fibrosis, respectively. No significant differences in the areas of GPR were comparable to that of APRI and FIB‐4.ConclusionGPR has a good correlation with LSM in assessing liver fibrosis and can be used as a noninvasive index for the assessment of liver fibrosis in patients with concomitant CHB and NAFLD.     

Nighttime sleep duration and risk of nonalcoholic fatty liver disease: the Dongfeng-Tongji prospective study

Background: To examine the association between self-reported nighttime sleep duration and nonalcoholic fatty liver disease (NAFLD) risk by comparing the incidence rates of NAFLD among healthy subjects with different sleep duration during the 5 years follow-up.

Methods: 8965 eligible NAFLD-free subjects with a mean age of 61.6 years (males, 43.4%) from Dongfeng-Tongji cohort study at baseline were enrolled in the study. Logistic regression analysis was used to estimate the association between sleep duration and incident NAFLD with potential confounders adjusted. Sleep duration was categorized into five groups:?<6?h, 6–7?h, 7–8?h, 8–9?h,?≥9?h.

Result: During the 5-years of follow-up, a total of 2,197 participants were newly diagnosed as NAFLD. Compared with those reported 7–8?h per day of nighttime sleep, the multivariable-adjusted odds ratio (95% confidence intervals) were 1.21 (1.07–1.38) for those who sleep 8–9?h/day, and 1.31 (1.13–1.52) for those who sleep over 9?h/day. However, no significant association was found with short nightly sleep duration (<7?h/day).

Conclusion: Long nighttime sleep duration was associated with a modestly increased risk of NAFLD in a middle-aged and elderly Chinese population.

• Key messages

• Long nighttime sleep duration was associated with a modestly increased risk of NAFLD in a middle-aged and elderly Chinese population.

• The effect of long nighttime sleep on the risk of incident NAFLD was attenuated greatly by body mass index (BMI) in men.

     

Serum levels of osteoprotegerin in the spectrum of nonalcoholic fatty liver disease

Abstract

Objective. Osteoprotegerin (OPG) is a member of the tumor necrosis factor superfamily with pleiotropic effects on inflammation, endocrine function and the immune system. Reduced OPG levels are related to insulin resistance. We tested the hypothesis that serum levels of OPG may be associated with nonalcoholic fatty liver disease (NAFLD). Material and methods. Four groups of patients were enrolled in the present study: subjects with definite nonalcoholic steatohepatitis (NASH, n = 56), borderline NASH (n = 26), simple fatty liver (n = 17) and healthy controls without evidence of liver disease (n = 58). Serum levels of OPG were measured by ELISA. Results. Concentrations of OPG were significantly lower in patients with definite NASH (median: 45 pg/mL, p < 0.001) and borderline NASH (57 pg/mL, p < 0.001) than in controls (92 pg/mL). The area under the ROC curve for distinguishing between steatohepatitis (definite NASH plus borderline NASH) and healthy controls using OPG was 0.82. The use of a cut-off level < 74 pg/mL for serum OPG levels yielded sensitivity and specificity values of 75.6% and 75.9%, respectively. Conclusions. Serum osteoprotegerin concentrations are reduced in patients with the more severe forms of NAFLD and may serve as a noninvasive biomarker to identify patients with NASH.     

胰高血糖素样肽-1改善非酒精性脂肪肝病作用机制的研究进展

非酒精性脂肪肝病（nonalcoholic fatty liver disease，NAFLD）与肥胖、胰岛素抵抗、2型糖尿病和血脂紊乱等密切相关。随着肥胖和糖尿病的发病率逐渐升高，NAFLD已成为全球最常见的慢性肝脏疾病。目前，NAFLD的主要治疗方法为改善生活方式、减轻体质量和应用降脂药物，尚缺乏特效的治疗药物。靶向胰高血糖素样肽-1（glucagon-like peptide-1，GLP-1）已被批准用于糖尿病和肥胖治疗，最近大量临床前和临床研究表明，GLP-1可通过多种机制缓解NAFLD。本文将GLP-1改善NAFLD的相关机制研究进展综述如下。