荷丹片联合二甲双胍治疗非酒精性脂肪肝伴代谢综合征的疗效观察

非酒精性脂肪性肝病（NAFLD）是一种常见慢性肝病,研究表明,NAFLD与代谢综合征（MS）密切相关。本研究应用荷丹片联合二甲双胍治疗NAFLD伴MS患者,观察其对脂肪肝及糖脂代谢等影响。     

张家口铁路职工非酒精性脂肪性肝病流行病学调查分析

非酒精性脂肪性肝病（NAFLD）是一种与胰岛素抵抗（IR）和遗传易感密切相关的代谢应激性肝脏损伤,疾病谱包括非酒精性单纯性脂肪肝（NAFL）、非酒精性脂肪性肝炎（NASH）及其相关肝硬化和肝细胞癌。NAFLD是欧美等西方发达国家肝功能酶学异常和慢性肝病最常见的原因,普通成人NAFLD患病率为20％～33％,其中NASH和肝硬化分别占10％～20％和2％～3％,在某些特定人群中则更高。在我国NAFLD患病率仅次于病毒性肝炎,排在第二位,约为15％。     

非酒精性脂肪性肝病回顾性分析及危险因素调查

非酒精性脂肪性肝病（NAFLD）是目前临床上最为常见的肝病之一,包括单纯性脂肪肝（NAFL）、脂肪性肝炎（NASH）和NASH相关性肝硬化3种病理类型。随着社会经济的发展,人民生活水平的日益提高,NAFLD的患病率逐年增加,发病呈低龄化趋势,已成为一种危害人类健康的常见的慢性肝脏疾病。我们就2010—2012年来我院就诊的298例NAFLD患者进行了回顾性分析,调查NAFLD与血压、腰围、体重指数（BMI）、血清生化指标变化的关系,预测影响NAFLD的危险因素,探讨防治措施以减少NAFLD的患病率及延缓其发生发展,结果报道如下。     

肠道菌群与非酒精性脂肪性肝病

非酒精性脂肪性肝病（non-alcoholic fatty liver disease, NAFLD）在全球范围内越来越常见,造成极大的疾病负担,故对其发生、发展及防治措施进行研究变得十分迫切。近年来,肠道菌群被认为是机体的一个重要的“特殊器官”,它参与机体的代谢并与相关疾病的发生、发展相关,与NAFLD的关系亦密切,值得深入探索,以期能寻找到防治NAFLD的新措施。     

非酒精性脂肪肝对药动学影响研究进展

非酒精性脂肪肝（NAFLD）是一种最常见的慢性肝病,严重威胁人类健康。在影响药物代谢的各种因素中,慢性肝病所起的作用最重要,可导致肝脏基因表达、mRNA及蛋白表达改变。非酒精性脂肪肝动物模型和非酒精性脂肪肝炎患者的研究结果显示,非酒精性脂肪肝时药物代谢酶及药物转运体发生显著改变。药物代谢酶和药物转运体在药物代谢过程中发挥重要作用,其改变可能影响药物在体内的清除,导致诸多临床药物的疗效、毒副作用甚至药物相互作用的发生。随着非酒精性脂肪肝的流行,越来越多的药物用于非酒精性脂肪肝患者。因此本文就非酒精性脂肪肝对药动学影响的研究进展作一综述。     

迁西县120例非酒精性脂肪肝临床特点和相关因素分析

非酒精性脂肪肝（NAFLD）是一种无过量饮酒史但病理学改变类似酒精性脂肪性肝病,以肝细胞脂肪变性和脂质储积为特征的临床病理综合征。常伴有不同程度的乏力、血清转氨酶及血脂的增高和B型超声（B超）改变。近年来,非酒精性脂肪肝发病率在逐年增高,已成为仅次于慢性病毒性肝炎、酒精性肝病的肝硬化前期病变之一,并为健康体检人群肝功能酶学异常的常见原因,国内关于NAFLD的流行病学调查报道较多,但由于地域和病例选择的差异,     

非酒精性脂肪性肝病合并高血压的影响因素分析

非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)是一种常见慢性肝病,包括非酒精性单纯性脂肪肝、非酒精性脂肪性肝炎及脂肪性肝炎相关的肝硬化.NAFLD发病率逐年增高,其病程中,往往并发代谢综合征.笔者对NAFLD并发高血压患者的临床生化指标进行分析,探讨其危险因素,为临床防治提供依据.     

非酒精性脂肪肝与代谢综合征的临床相关性分析

目的：探讨非酒精性脂肪肝（NAFLD）与代谢综合征（MS）相关指标变化的关系,并进行临床相关性研究。方法：选择本院诊断的NAFLD患者共122例作为研究对象,检测其酶学、代谢指标及并发症情况。结果：与单纯NAFLD组比较,NAFLD合并MS组患者的BMl、TG、收缩压、舒张压、空腹血糖明显增高,差异具有统计学意义（P〈0．05）;血清总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）及血尿酸差异无统计学意义（P〉0．05）;两组并发症之间差异具有统计学意义（P〉0．05）。结论：NAFLD合并MS患者的代谢指标异常及并发症发生率高,临床医师应重视,并给与患者合理的建议。     

从典型病例谈NAFLD的诊断和治疗

非酒精性脂肪性肝病（NAFLD）是指除外过量饮酒和其他明确的损肝因素所致的肝细胞内脂肪沉积,其疾病谱包括非酒精性单纯性脂肪肝（nonalcoholic simple fatty liver,NAFL）、非酒精性脂肪性肝炎（nonalcoholic steatohepatitis,NASH）及其相关肝硬化和肝细胞癌。非酒精性脂肪性肝病的发病与肥胖、糖尿病、代谢综合征密切相关,被认为是代谢综合征在肝脏的表现。     

白藜芦醇对高尿酸介导的非酒精性脂肪肝大鼠血脂及肝组织脂肪变的影响

<正>非酒精性脂肪性肝病(NAFLD)是目前最常见的肝脏问题,可能会进展到其他肝脏疾病,如非酒精性脂肪性肝炎、肝纤维化、肝硬化,甚或肝癌。NAFLD是多种因素导致的一系列肝细胞脂肪浸润~([1]),其中饮食条件不容忽视。近期研究表明,血清尿酸升高与脂肪肝密切相关~([2,3]),并影响其严重程度~([4])。目前尚没有药物治疗证实对NAFLD有确切疗效。白藜芦醇(resveratrol,Res),化学名为3,4,5-三羟基二苯乙烯,是     

Hyperuricaemia and non-alcoholic fatty liver disease (NAFLD): a relationship with implications for vascular risk?

Both elevated levels of uric acid and non-alcoholic fatty liver disease (NAFLD) have been associated with increased vascular risk. Furthermore, certain drugs (e.g. lipid and blood pressure lowering) that decrease)cardiovascular risk and improve/preserve renal function were shown to influence serum uric acid (SUA) levels and/or NAFLD. A link between hyperuricaemia and NAFLD has also been suggested. This review considers the associations between hyperuricaemia, NAFLD and vascular risk. We also discuss the effects of different drug treatments on SUA and NAFLD. As NAFLD is a very common condition, future work in this field is needed with regard to a more practical definitive diagnosis, evidence- based treatments and a better understanding of the possible links between NAFLD, elevated SUA levels, cardiovascular disease and chronic kidney disease. Whether treating hyperuricaemia and NAFLD will translate into a reduced risk of vascular events requires further investigation.     

Effects of Genistein, Apigenin, Quercetin, Rutin and Astilbin on serum uric acid levels and xanthine oxidase activities in normal and hyperuricemic mice

Flavonoids are widely found in plants and many of them possess biological and pharmacological activities. In the present study, we assessed the effects of the flavonoids Genistein, Apigenin, Quercetin, Rutin and Astilbin on xanthine oxidase (XO) activities in vitro, and in serum and the liver. The effects of the flavonoids on serum uric acid levels were also measured in vivo. In vitro studies indicated that the flavonoids tested did not significantly affect XO activity. However, significant increases and decreases in XO activities were observed in vivo. Moreover, serum XO activity was correlated with serum uric acid levels, while no correlation was observed for liver XO activity. The present study showed that serum uric acid levels in mice treated with the flavonoids tested here are higher than control levels. Therefore, the flavonoids tested here are not candidates for replacing Allopurinol as a treatment to reduce serum uric acid levels.     

染料木素等5种黄酮类物质对小鼠血清尿酸水平及黄嘌呤氧化酶活性的影响

目的探讨黄酮类化合物染料木素、芹菜素、槲皮素、芦丁和落新妇苷体外对黄嘌呤氧化酶活性的影响,对正常小鼠血清和肝脏黄嘌呤氧化酶活性的影响,同时评价对小鼠血清尿酸水平的作用。方法采用改良的紫外分光光度法测定染料木素、芹菜素、槲皮素、芦丁和落新妇苷体外对黄嘌呤氧化酶的抑制作用,采用分光光度法研究对小鼠血清和肝脏黄嘌呤氧化酶活性的影响,以磷钨酸法测定对小鼠血清尿酸水平的作用。结果体外实验表明黄酮类化合物染料木素、芹菜素、槲皮素、芦丁和落新妇苷体外对黄嘌呤氧化酶活性无明显影响。体内实验观察到这5种黄酮类化合物能够显著升高或降低黄嘌呤氧化酶的活性;而且,血清尿酸水平与血清黄嘌呤氧化酶活性密切相关,与肝脏黄嘌呤氧化酶活性无明显关联。用这些黄酮类化合物给药的小鼠血清尿酸水平都高于正常对照组。结论这5种黄酮类化合物不能够作为替代别嘌醇的药物用来降低血清尿酸水平。     

Hyperuricemia is associated with histological liver damage in patients with non-alcoholic fatty liver disease

Aliment Pharmacol Ther 2011; 34: 757–766

Summary

Background Hyperuricemia has been associated with metabolic disorders. In this line recent studies observed an independent link between higher uric acid serum levels and clinical diagnosis of non‐alcoholic fatty liver disease (NAFLD). Aims We aimed to assess the potential association between uric acid serum levels and histological liver damage in a homogeneous cohort of biopsy‐proven NAFLD patients. Methods Consecutive NAFLD patients (n = 166), assessed by liver biopsy (Kleiner score), anthropometric, biochemical and metabolic features, were included. Enzymatic colorimetric test was used for serum uric acid assays (Roche Diagnostics GmbH, Mannheim, Germany). Hyperuricemia was diagnosed when uric acid serum levels were >7 mg/dL in men, and >6 mg/dL in women. Results Mean uric acid serum level was 5.75 mg/dL, and about 20% of patients had hyperuricemia, that was independently associated with younger age (OR 0.951, 95% CI 0.918–0.984, P = 0.004), lobular inflammation (OR 2.144, 95% CI 1.055–4.357, P = 0.03) and steatosis grade (OR 1.859, 95% CI 1.078–3.205, P = 0.02), by multivariate logistic regression analysis. Female gender (OR 2.656, 95% CI 1.190–5.928, P = 0.01), higher HOMA index (OR 1.219, 95% CI 1.043–1.426, P = 0.01), and hyperuricemia (OR 4.906, 95% CI 1.683–14.296, P = 0.004) were linked to NAFLD activity score (NAS) ≥ 5 by multiple logistic regression analysis. Conversely, higher HOMA index (OR 1.140, 95% CI 1.001–1.229, P = 0.04), and NAS (OR1.954, 95% CI 1.442–2.649, P < 0.001) were independently associated with significant fibrosis by logistic regression analysis. Conclusions In NAFLD patients, hyperuricemia is independently associated with the severity of liver damage, representing, in this setting of patients, together with insulin resistance, a potential new therapeutic target in future intervention trials.     

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.     

sRAGE is associated with low waist circumference and Hb levels in NAFLD

Advanced glycation end products (AGEs) and the receptor RAGE interaction is involved in nonalcoholic fatty liver disease (NAFLD). Although exogenously administered soluble RAGE (sRAGE) has been shown to block the harmful effects of AGEs in animal models, there is still controversy about the role of sRAGE in humans. We examined here which anthropometric, metabolic and clinical variables were independent correlates of sRAGE levels in NAFLD patients. The study involved 77 biopsy-proven, unmedictaed NAFLD patients (44 male and 33 female) with a mean age of 43.4±13.0 years old. We examined which anthropometric, metabolic and clinical variables, including liver steatosis and fibrosis markers, are independently associated with serum levels of sRAGE. Mean serum levels of sRAGE were 710.7±290.2 pg/mL. Univariate analysis revealed that waist circumference (inversely), hemoglobin (inversely), number of white blood cells (inversely), total-bilirubin (inversely), free fatty acid (inversely), ferritin (inversely), and HbA1c (inversely) were significantly correlated with serum levels of sRAGE. In multiple stepwise regression analysis, waist circumference (p<0.01, inversely) and hemoglobin (p<0.01, inversely) were independently associated with serum levels of sRAGE (R²=0.176). The present study reveals that low serum levels of sRAGE are independently associated with waist circumference and hemoglobin in patients with NAFLD.     

The genetic deletion of Mas abolishes salt induced hypertension in mice

Flavangenol, one of several pine bark extract products, is expected to prevent metabolic diseases with its potent antioxidant effect, its anti-obesity effect and its improvement of insulin sensitivity. In this study, targeting the liver as one of the organs that plays an important role in energy metabolism, Flavangenol was investigated for its effect on non-alcoholic fatty liver disease (NAFLD), its action mechanism and its active ingredients, using in vivo and in vitro experiment systems. Flavangenol suppressed intrahepatic fat accumulation in Western diet-loaded Tsumura Suzuki Obese Diabetes (TSOD) mice, which develop various metabolic diseases. In addition, Flavangenol significantly increased the mRNA expression levels of fatty acid oxidative enzymes (peroxisomal proliferator-activated receptor α, acyl-CoA oxidase, carnitine palmitoyltransferase). In order to investigate the direct effect of Flavangenol on the liver, an in vitro fatty liver model prepared by adding a free fatty acid to human liver cancer cells (HepG2 cells) was used. In this model, Flavangenol significantly suppressed intracellular fat accumulation. Procyanidin B1, one of the major components of Flavangenol, also suppressed fat accumulation and induced mRNA expression of the fatty acid oxidative enzymes. As mentioned above, Flavangenol showed a significant suppressive effect in the NAFLD model, and it was suggested that the molecular mechanism is induction of fatty acid oxidation, with the effect mainly attributed to procyanidin B1.     

Therapeutic voyage of synthetic and natural xanthine oxidase inhibitors

Xanthine oxidase (XO) inhibitors are commonly used to treat gout, nephropathy, and renal stone diseases related to hyperuricemia. However, recent research has shown that these inhibitors may also have potential benefits in preventing vascular diseases, including those affecting the cerebrovasculature. This is due to emerging evidence suggesting that serum uric acid is involved in the growth of cardiovascular disease, and XO inhibition can reduce oxidative stress in the vasculature. There is a great interest in the development of new XO inhibitors for the treatment of hyperuricemia and gout. The present review discusses the many synthetic and natural XO inhibitors that have been developed which are found to have greater potency.     

Hypouricemic effect of the methanol extract from Prunus mume fruit in mice

Context: The fruit of the Prunus mume Sieb. et Zucc (Rosaceae) is used as a health food or medicinal material in traditional herb medicine for a long time in Eastern Asian countries.

Objective: Our present study investigated the hypouricemic effect of the methanol extract from P. mume fruit (MPMF) in mice with potassium oxonate-induced hyperuremia.

Materials and methods: Effect of MPMF (35, 70 and 140 mg/kg, p.o.) administrated for 7 days on the serum, liver, urinary uric acid levels and liver xanthine oxidase (XO) activity were assessed in mice.

Results: Hyperuricemic mice induced by potassium oxonate demonstrated an elevation in serum and liver uric acid levels (11.0 mg/dL and 0.52 mg/g tissue) and a reduction in urinary uric acid levels (49.9 mg/dL). Oral administration of 140 mg/kg MPMF for 7 days reversed the abnormalities in serum, liver and urinary uric acid levels (7.1 mg/dL, 0.37 mg/g tissue and 69.7 mg/dL, respectively). In addition, 70 and 140 mg/kg MPMF (3.1 and 2.9 nmol/min per mg protein) inhibited liver XO activity compared with hyperuricemic mice (3.9 nmol/min per mg protein).

Discussion and conclusion: The results indicated that the beneficial hypouricaemic effect of MPMF may be mediated, at least in part, by inhibiting XO activity in the liver. Our study suggests that P. mume and its extracts may have a considerable potential for development as an anti-gout agent for clinical application.     

ω-3多不饱和脂肪酸治疗非酒精性脂肪性肝病的研究进展

非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)是由多种危险因素,如营养过剩、胰岛素抵抗(insulin resistance,IR)及相关代谢紊乱等诱导的慢性肝损伤,是代谢综合征在肝脏的病理表现。其病程的进展表现为非酒精性单纯性脂肪肝(nonalcoholic simple fatty liver,NAFL)、非酒精性脂肪性肝炎(nonalcoholic steatohepatitis,NASH)、脂肪性肝纤维化和脂肪性肝硬化。NAFLD患病率逐年升高,已成为我国最常见的慢性肝病之一。NAFLD的治疗主要为增加运动、健康饮食等基础治疗,药物治疗尚未达成共识。ω-3多不饱和脂肪酸(ω-3 polyunsattrated fatty acids,ω-3PUFAs)具有调节血脂的功能。NAFLD患者ω-3PUFAs水平较低,增加饮食中的ω-3PUFAs可以延缓病情进展,改善肝脏脂代谢的失衡和肝细胞的炎性损伤。本文主要就ω-3PUFAs对NAFLD治疗的研究进展作一综述。