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.     

Visceral adiposity index is associated with significant fibrosis in patients with non-alcoholic fatty liver disease

Aliment Pharmacol Ther 2012; 35: 238–247

Summary

Background Metabolic factors have been associated with liver damage in patients with non‐alcoholic fatty liver disease (NAFLD). Aims To test a new marker of adipose dysfunction, the visceral adiposity index (VAI), in NAFLD patients to assess whether or not it is associated with host factors, and to investigate a potential correlation with histological findings. Methods One hundred and forty‐two consecutive NAFLD patients were evaluated by liver biopsy, and clinical and metabolic measurements, including insulin resistance with the homeostasis model assessment (HOMA), and VAI by using waist circumference, body mass index, triglycerides and HDL. Serum levels of TNFα, IL‐6, adiponectin and leptin were also assessed. All biopsies were scored for NAFLD activity score (NAS) and its components, and for staging (Kleiner). Results By multiple linear regression analysis, VAI was independently associated with higher HOMA (P = 0.04), and fibrosis (P = 0.04). In addition, an independent association was found between higher VAI and lower adiponectin levels (P = 0.002). Higher HOMA (OR 1.149, 95% CI 1.003–1.316, P = 0.04), higher VAI (OR 1.446, 95% CI 1.023–2.043, P = 0.03), lobular inflammation (OR 3.777, 95% CI 1.771–8.051, P = 0.001), and ballooning (OR 2.884, 95% CI 1.231–6.757, P = 0.01) were correlated with significant fibrosis (F2–F4) on multiple logistic regression analysis. In particular, the prevalence of significant fibrosis progressively increased from patients with a VAI ≤ 2.1 and HOMA ≤ 3.4 (26%) to those with a VAI > 2.1 and HOMA > 3.4 (83%). Conclusions In NAFLD patients, visceral adiposity index is an expression of both qualitative and quantitative adipose tissue dysfunction and, together with insulin resistance, is independently correlated with significant fibrosis.     

Health-related quality of life in patients with non-alcoholic fatty liver disease

BACKGROUND: The relative impact of non-alcoholic fatty liver disease (NAFLD) on health-related quality of life (HRQL) compared to other chronic liver diseases has not been fully explored. AIM: To compare the domain scores of the 29-item Chronic Liver Disease Questionnaire (CLDQ) for patients with NAFLD to those with chronic hepatitis B and chronic hepatitis C. METHODS: A HRQL questionnaire, CLDQ, was routinely administered to patients attending a liver clinic. Additional clinical and laboratory data were obtained on patients with NAFLD, chronic hepatitis B, and chronic hepatitis C from our quality of life database. Scores for each of the six CLDQ domains were compared using one-way anova and multiple regression. RESULTS: Complete data were available for 237 patients. NAFLD patients scored lowest on multiple CLDQ domains. Based on the bivariate data, NAFLD patients have the poorest HRQL, followed by chronic hepatitis C and chronic hepatitis B patients. Multivariate analysis showed that some specific domain score correlations remained significant for NAFLD diagnosis, cirrhosis, gender, and body mass index. CONCLUSION: NAFLD patients had significantly lower quality of life scores compared with patients with hepatitis B or hepatitis C on multiple CLDQ domains, suggesting that HRQL was severely impaired in patients with NAFLD.     

水林佳治疗非酒精性脂肪性肝病疗效观察

目的观察水林佳（水飞蓟宾-磷脂复合物）治疗非酒精性脂肪性肝病的临床疗效。方法将56例患者随机分为2组,治疗组予水林佳口服,对照组予硫普罗宁口服,均3个月为1个疗程,疗程结束后,观察临床症状、ALT、AST、TC、TG和超声影像的变化。同时观察2组患者用药期间的不良反应。结果治疗组和对照组总有效率分别为89.3%及71.4%,治疗组明显高于对照组,2组比较差异有显著性（P〈0.05）。治疗组在改善患者临床症状、肝功能、血脂及超声影像方面疗效确切,无明显不良反应。结论水林佳治疗非酒精性脂肪性肝病有较好临床疗效。     

水林佳治疗非酒精性脂肪肝的疗效观察

目的:探讨水林佳治疗非酒精性脂肪肝的疗效。方法:随机选择非酒精性脂肪肝患者90例,试验组46例,服用水林佳105mg,3次/日;对照组44例,口服硫普罗宁100 mg,3次/日,观察期为3个月。治疗前后检测肝转氨酶、血胆固醇、甘油三酯、肝纤维谱及超声影像变化。同时观察两组患者用药期间的不良反应。结果:治疗结束时,试验组ALT、AST、TC、TG及HA、LN、PC-Ⅲ均明显下降,肝脏影像学也有明显改善。对照组虽ALT、AST有所下降,但HA、LN、PC-Ⅲ和肝脏影像学无明显改善。观察期间两组均未出现明显不良反应。结论:水林佳具有保肝、降血脂、改善肝纤维化的作用,对非酒精性脂肪肝有治疗作用。     

非酒精性脂肪肝患者血清鸢尾素水平变化的研究

目的：探讨不同病变程度非酒精性脂肪肝（non-alcoholic fatty liver disease，NAFLD）患者血清鸢尾素（Irisin）水平的变化情况及Irisin与其他生化指标的相关性。方法选取135例NAFLD患者（轻度脂肪病变患者73例，中、重及极重度脂肪病变患者共62例）作为观察组，健康体检者150例为对照组，全自动生化分析仪测定其各项血脂指标水平及各项生化指标；酶联免疫吸附法测定血清Irisin水平；依据稳态模型评估法计算胰岛素抵抗指数，并同时测量身高、体质量等多项基线指标。结果血清Irisin水平与对照组相比，轻度NAFLD患者，中、重及极重度NAFLD患者均增高（P＜0．05）；其它各项指标与对照组相比，NAFLD组患者的BMI、TC、TG、AST、ALT、收缩压、舒张压、腰围、臀围、血糖、FINS及HOMA-IR均呈现不同程度升高，差异多有统计学意义（P＜0．05）；而年龄、性别、HDL-C、LDL-C水平差异多无统计学意义（P＞0．05）。Spearman相关分析结果显示，研究对象血清Irisin水平与BMI（rs ＝0．168，P＜0．05），FINS（rs ＝0．204，P＜0．01），HOMA-IR（rs ＝0．205，P＜0．05），AST（rs＝0．149，P＜0．05），腰围（rs ＝0．147，P＜0．05）呈现正相关，而与TC（rs ＝－0．205，P＜0．05），HDL-C（rs ＝－0．165，P＜0．05）呈现负相关；FINS、HOMA-IR、AST是影响血浆Irisin水平的独立相关因素。结论血清Irisin水平在NAFLD组患者中较正常人群增高，且在轻度NAFLD患者中水平最高。     

Histological progression of non-alcoholic fatty liver disease in Chinese patients

BACKGROUND: Non-alcoholic fatty liver disease is an important cause of chronic hepatitis and cryptogenic cirrhosis. The natural history of non-alcoholic fatty liver disease is not well understood especially in Asian populations. AIM: To investigate the histological progression in Chinese patients with biopsy-proven non-alcoholic fatty liver disease. METHODS: Chinese patients who had liver biopsy at least 3 years ago and confirmed to have non-alcoholic fatty liver disease were invited for a second liver biopsy. Clinical and laboratory parameters related to their liver function and metabolic syndrome were recorded and analysed. Liver biopsies were scored for the degree of steatosis, necroinflammation and fibrosis. Correlation coefficients were calculated to assess the association between changes in histological scores and metabolic parameters. RESULTS: Seventeen patients who had been followed up for a median period of 6.1 (range: 3.8-8.0) years underwent a second liver biopsy. Nine (53%) patients had progressive disease with worsening of fibrosis score. No statistically significant correlation was found between the changes in histological scores and metabolic parameters. Seven patients developed hypertension or diabetes mellitus during the period of follow-up. CONCLUSIONS: Non-alcoholic fatty liver disease is a progressive disease in Chinese patients as in their Caucasian counterparts. Diagnosis of non-alcoholic fatty liver disease may predate development of new components of metabolic syndrome.     

从非酒精性脂肪性肝病到代谢相关脂肪性肝疾病

非酒精性脂肪性肝病（non-alcoholic fatty liver disease,NAFLD）的患病率逐年上升,世界对该疾病的认识也逐渐深入。多年来,在对该领域不断的探索中发现术语NAFLD的局限性,因此国际多名专家经过多年讨论,最终联手提出了新术语“代谢相关脂肪性肝疾病（metabolic associated fatty liver disease, MAFLD）”,然而这一术语在过去几年饱受争议。从NAFLD到MAFLD,给科研及临床工作带来的影响是不容置疑的。因此,该文简要总结了现有的研究结论,通过多方面对比NAFLD和MAFLD,加深临床医师对MAFLD的认识。     

Bile acid receptors in non-alcoholic fatty liver disease

Accumulating data have shown that bile acids are important cell signaling molecules, which may activate several signaling pathways to regulate biological processes. Bile acids are endogenous ligands for the farnesoid X receptor (FXR) and TGR5, a G-protein coupled receptor. Gain- and loss-of-function studies have demonstrated that both FXR and TGR5 play important roles in regulating lipid and carbohydrate metabolism and inflammatory responses. Importantly, activation of FXR or TGR5 lowers hepatic triglyceride levels and inhibits inflammation. Such properties of FXR or TGR5 have indicated that these two bile acid receptors are ideal targets for treatment of non-alcoholic fatty liver disease, one of the major health concerns worldwide. In this article, we will focus on recent advances on the role of both FXR and TGR5 in regulating hepatic triglyceride metabolism and inflammatory responses under normal and disease conditions.     

Adipokines and cytokines in non-alcoholic fatty liver disease

Background  Several adipocytokines have been implicated in the pathogenesis non-alcoholic fatty liver disease (NAFLD).
Aim  To assess adipocytokines in NAFLD patients and controls.
Methods  A total of 95 patients (26 non-alcoholic steatohepatitis (NASH), 19 simple steatosis (SS), 38 obese controls and 12 non-obese controls) were included. Fasting serum insulin, glucose, visfatin, resistin, adiponectin, tumour necrosis factor-α (TNF-α), interleukin-8 (IL-8) and IL-6 were determined. Univariate and multivariate analyses were used to compare groups and determine associations.
Results  Serum TNF-α and IL-8 were higher in NAFLD patients when compared with both obese and non-obese controls. Analysis involving all patients revealed a significant correlation between serum TNF-α and IL-8 ( P  < 6.319e−08), and between IL-6 and IL-8 ( P  < 5.271e−15). Homeostatic model assessment scores negatively correlated with adiponectin in NAFLD ( P  < 0.0032). Serum visfatin was higher in all three obese groups than in non-obese controls ( P  < 0.02, P  < 0.002 and P  < 0.008). Visfatin in NASH patients was lower than SS and obese controls. Although TNF-α was associated with NAFLD ( P  < 0.02), it was interdependent on visfatin. In comparison to SS, four factors were independently associated with NASH: age, alanine aminotransferase, IL-8 and adiponectin ( P  < 0.05). Multivariate analysis indicated that TNF-α was the only independent predictor of fibrosis in NASH ( P  < 0.0004).
Conclusion  These findings support a complex interaction between adipocytokines and the pathogenesis of NAFLD.     

非酒精性脂肪性肝病的研究进展及认识

非酒精性脂肪性肝病是引起肝酶升高及慢性肝病的常见病因,其发病趋势呈低龄化且增长迅速,已成为一个不可忽视的全球健康卫生问题.本文综述非酒精性脂肪性肝病的最新研究进展及相关临床认识.     

非酒精性脂肪性肝病发病机制的研究进展

非酒精性脂肪性肝病（NAFLD）是指与过量饮酒无关的临床综合征,主要病理改变包括肝细胞弥漫性脂肪变性和脂肪堆积。NAFLD动物模型表现出显著的肝脏微循环障碍,关于其形成机制,被广为接受的为＂二次打击＂学说。该学说认为肥胖、胰岛素抵抗等因素作为＂第一次打击＂,导致肝脏中脂质堆积,形成单纯性脂肪肝,增加了＂第二次打击＂造成的肝脏损伤的易感性,这些因素包括炎症、枯否细胞功能障碍、氧化应激、线粒体障碍、脂肪因子调节紊乱等,导致非酒精性脂肪性肝炎甚至纤维化等更严重疾病的发生。     

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。     

非酒精性脂肪性肝病临床特点分析

目的 探讨非酒精性脂肪性肝病(NAFLD)与代谢综合征关系及相关危险因素.方法 回顾性分析在我院健康体检764例在职教师的体检资料,并对其相关资料进行统计分析.结果 NAFLD发病率高达27.23%,NAFLD组高血压、2型糖尿病、血脂异常、肥胖、代谢综合征(MS)发病率明显高于对照组;三酰甘油、总胆固醇、低密度脂蛋白胆固醇、空腹血糖、收缩压、舒张压、体质量指数均高于对照组,高密度脂蛋白胆固醇低于对照组(P<0.05).结论 NAFLD发生率高,与代谢综合征(MS)关系密切.高血压、2型糖尿病、血脂异常、肥胖是NAFLD发生的危险因素.     

缬沙坦胶囊治疗伴有非酒精性脂肪肝的高血压患者的疗效观察

目的探讨缬沙坦胶囊治疗伴有非酒精性脂肪肝（NAFLD）的高血压患者的疗效。方法将符合纳入标准患者随机分成试验组和对照组。试验组给予缬沙坦胶囊;对照组给予氨氯地平片。比较两组血压、肝脏超声、肝功能、血脂、胰岛素抵抗指数（RI）的差别及临床疗效。结果缬沙坦胶囊组总有效率（93.24%）显著高于对照组（81.08%）,差异有统计学意义（χ^2=4.891,P=0.027）;治疗后,试验组谷丙转氨酶、胆固醇、甘油三酯、低密度脂蛋白及RI均显著低于对照组,差异有统计学意义（P〈0.05）。结论缬沙坦胶囊治疗伴有NAFLD的高血压患者具有更好疗效。