脂必妥治疗非酒精性脂肪性肝炎的临床观察

目的 通过常规护肝降酶治疗和联用调脂治疗对比了解地奥脂必妥对非酒精性脂肪性肝炎的临床疗效及安全性影响。方法 将80例非酒精性脂肪性肝炎（NASH）患者随机分为A、B两组。A组使用护肝降酶药物治疗4周，B组使用上述治疗联合地奥脂必妥口服治疗4周。结果 A组ALT、AST、Tch、TG降低不明显（P〉0．05）；B组的上述指标明显下降到目标水平，与A组比较疗效有显著性差异（P〈0．01）。结论 对NASH患者联用地奥脂必妥和护肝降酶治疗疗效好，可明显降低Tch、TG，并促进ALT、ASF好转，且不会导致肾功能和血糖代谢异常。     

233例非酒精性脂肪性肝炎口服二氯醋酸二异丙胺治疗的临床分析

目的：观察口服二氯醋酸二异丙胺治疗非酒精性脂肪性肝炎(NASH)的疗效。方法：将233例NASH患者随机分为治疗组和对照组，两组均可口服维生素C，维生素E，肝太乐，治疗组加用二氯醋酸二异丙胺6个月。在治疗前后观察，血脂代谢及肝脏酶改善情况。结果：二氯醋酸二异丙胺治疗组在改善肝功能及降低血脂方面，与对照组相比较均有显著差异性。但两组在血糖及胰岛素水平上无显著性差别。结论：口服二氯醋酸二异丙胺不仅有改善肝功能，而且有调节血脂代谢的作用，但不影响血糖及胰岛素水平。     

非酒精性脂肪性肝炎的治疗

非酒精性脂肪性肝病（nonalcoholic fatty liver diseases，NAFLD）是指l临床病理上从仅出现单纯性脂肪肝到发生非酒精性脂肪性肝炎（nongtlcoholic steatohepatitis，NASH）和进一步演变为肝硬化的一种疾病，其中NASH是指兼具肝脂肪变性及肝脏炎症和（或）纤维化的生化和组织学证据的NAFLD，最初于1980年由Ludwig等人命名。一般所指的是与代谢综合征（或称X综合征，包括腹型肥胖、脂肪肝、Ⅱ型糖尿病、高脂血症和高血压等）有关的原发性NASH。目前，随着城市化的进展，生活行为方式的改变，高脂肪高热量的饮食，NASH在东西方国家均有增长趋势。据美国及西方国家报道约20％～30％的成人有肝内脂肪过度积聚，这些人群中约10％（或2％～3％的成人）符合NASH的诊断，而大约1／3以上的NASH患者可能因持续性肝损伤而导致纤维化进展，与慢性病毒性肝炎和酒精性肝病一样可发展到终末期肝硬化并出现肝硬化严重并发症。     

护肝降脂方治疗非酒精性脂肪性肝炎疗效观察

目的:观察自拟护肝降脂方治疗非酒精性脂肪性肝炎的临床疗效。方法:将60例患者随机分为治疗组30例和对照组30例,治疗组予中药护肝降脂方治疗,对照组口服水飞蓟宾片、熊去氧胆酸片,两组均服用3个月;观察两组临床疗效及治疗后患者肝功能、甘油三酯(TG)、总胆固醇(TCh)、肝脏B超影像变化情况。结果:治疗组临床总有效率为86.6%,对照组为63.3%,两组比较有显著性差异(P<0.05);治疗组患者ALT、AST、GGT、TCh、TG等值与对照组比较,差异有显著性(P<0.05)。结论:中药护肝降脂方对非酒精性脂肪性肝炎有较好的临床疗效,可明显改善患者肝功能、血脂、B超影像。     

低频治疗仪治疗非酒精性脂肪性肝炎50例临床护理

2005年7月-2007年7月，我们采用低频治疗仪治疗50例非酒精性脂肪性肝炎患者，经精心护理，效果满意。现报告如下。     

姜黄素防治大鼠非酒精性脂肪性肝炎的实验研究

目的探讨姜黄素防治非酒精性脂肪性肝炎（NASH）的作用及机制。方法采用高脂饮食复制大鼠NASH模型。随机分为正常对照组、空白模型组、姜黄素防治组、东宝肝泰防治组。检测肝功能、血脂变化、肝匀浆超氧化物歧化酶（SOD）活性、丙二醛（MDA）含量的变化，观察肝细胞脂肪变性、炎症活动程度。结果与空白模型组相比，姜黄素防治组大鼠血清ALT、AST、TG、TCH明显降低（P〈0．01）；肝匀浆中SOD活性升高（P〈0．01）、MDA含量显著降低（P〈0．01），脂肪变性、炎症活动程度皆有改善（P〈0．05），部分作用优于东宝肝泰防治组（P〈0．01或P〈0．05）。结论姜黄素对NASH有明显的防治作用，其作用机制与其能减少脂类积聚、抗脂质过氧化有关。     

清肝消脂汤治疗非酒精性脂肪性肝炎疗效观察

目的:观察清肝消脂汤联合阿拓莫兰治疗瘀血湿热内阻型非酒精性脂肪性肝炎(NASH)的临床疗效。方法:将符合入选条件的80例患者随机分成治疗组和对照组各40例。对照组在调整饮食结构、适量有氧运动等基础治疗的同时,给予阿拓莫兰治疗,治疗组在对照组的基础上,加服清肝消脂汤,疗程3个月,观察两组病例中医临床症状、体征和CT检查(肝/脾CT值)、肝功能、血脂疗效的变化。结果:清肝消脂汤联合阿拓莫兰能明显改善NASH患者肝脏影像学变化,减轻临床症状,改善和恢复肝功能,降低患者血清甘油三脂、胆固醇的含量,其总有效率为92.5%,优于对照组的60.0%(P<0.01)。结论:中西医结合治疗NASH疗效显著。     

硫普罗宁联合丹参注射液治疗非酒精性脂肪性肝炎

目的观察硫普罗宁联合丹参注射液治疗非酒精性脂肪性肝炎的临床疗效。方法66例非酒精性脂肪性肝炎随机分为治疗组36例、对照组30例,治疗组用硫普罗宁联合丹参注射液治疗,对照组用硫普罗宁治疗,4周为1疗程,观察治疗前后的肝功能变化。结果治疗组患者综合疗效与对照组比较,有显著统计学意义(P<0.05)。结论硫普罗宁联合丹参注射液对非酒精性脂肪性肝炎疗效显著。     

水林佳联合二甲双胍治疗非酒精性脂肪性肝炎疗效观察

目的:观察水林佳联合二甲双胍对非酒精性脂肪性肝炎(non-alcoholic steatohepatitis,NASH)的临床疗效.方法:将2006年2月～2007年10月收治的56例NASH随机分为治疗组和对照组,每组28例,两组均予水林佳70 mg每日3次口服,治疗组加用二甲双胍250 mg每日3次口服,疗程均为3个月.观察治疗前后生化指标、肝脏B超及CT变化,药物不良反应.结论:两组疗程结束后丙氨酸转氨酶、天冬氨酸转氨酶均较治疗前明显下降(P＜0.01,P＜0.05),组间比较,治疗组显著低于对照组(P＜0.05);治疗组治疗后血脂较治疗前显著降低(P＜0.01),治疗后与对照组比较显著降低(P＜0.01);对照组治疗前后血脂无显著差异(P＞0.05).两组有少数患者出现轻度食欲缺乏等不适,可自行恢复.结论:水林佳联合二甲双胍对于NASH具有良好疗效,且无明显不良反应.     

中医药治疗非酒精性脂肪性肝炎临床研究的系统评价

目的系统评价中医药治疗非酒精性脂肪性肝炎的有效性及安全性。方法计算机检索中国期刊全文数据库、中国科技期刊全文数据库、中国生物医学文献数据库、PubMed,检索时限均为从建库至2009年11月。纳入中医药治疗非酒精性脂肪性肝炎的临床随机对照试验,根据脏腑论治原则进行分层,使用Cochrane协作网推荐的方法进行文献质量评价及Meta分析。结果共纳入22个研究,其中18个属于低质量研究,4个属于中等质量研究。Meta分析结果显示:①从肝论治的中药在痊愈率、总有效率、肝功能、血脂方面与西药治疗无差别;②从肝脾论治的中药在痊愈率、有效率、肝功能、甘油三酯(TG)和低密度脂蛋白(LDL-C)方面疗效均优于西药,但在调节TG和低密度脂蛋白(HDL-C)方面与西药治疗无差别;③从肝脾肾论治的中药在治愈率、总有效率、肝功能、血脂方面疗效均优于西药,在提高HDL-C方面与西药疗效相当;④从肝肾论治的中药,在痊愈率、总有效率、肝功能及LDL-C、HDL-C方面优于西药,但对TC、TG的疗效与西药治疗无差别。结论中医药治疗非酒精性脂肪性肝炎有明显疗效;从肝脾肾辨证论治在痊愈率、有效率和改善肝功能方面均明显优于西药;中药治疗未发现严重不良反应。     

Vitamin E treatment in patients with nonalcoholic steatohepatitis: A six-month, open-label study of sixteen patients

Background

Free radicals have a pivotal role in the pathogenesis of nonalcoholic steatohepatitis (NASH). Decreasing oxidative stress might have beneficial effects on the biochemical and histologic progression of this disease.

Objective

We aimed to determine the therapeutic effect of vitamin E, a potent antioxidant, on liver enzymes and histology in NASH.

Methods

This 6-month, open-label study was conducted at the Departments of Gastroenterology and Pathology, Gazi University School of Medicine (Ankara, Turkey). Patients aged 18 to 70 years with biopsy-proven NASH were included in the study. All patients received vitamin E 800 U/d in 2 divided doses, orally (capsules) for 6 months. Patients were not advised to change their exercise or dietary habits. Body mass index (BMI) was calculated at months 0 (baseline) and 6. Histologic scoring of steatosis, necroinflammatory grade, and fibrosis stage was performed at 0 and 6 months. Liver enzyme activities (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP], and gamma-glutamyltransferase [GGT]) were monitored monthly. Control biopsy specimens were obtained at the end of the treatment. All of the liver biopsies were read by a single pathologist (G.A.) who was blinded to the clinical, laboratory, and histopathologic data, as well as the sequence of liver biopsies. Assessments of compliance and tolerability of treatment were performed using a pill count and patient interview, respectively, at the end of each month.

Results

Sixteen patients (12 men, 4 women; mean [SD] age, 45.5 [6.9] years [range, 37-60 years]) were enrolled. All patients completed 6 months of treatment. Mean BMI did not change significantly from baseline. Significant improvements in mean (SD) serum liver enzyme activities were observed at 6 months compared with baseline (ALT: 38.6 [16.3] U/L vs 84.8 [22.1] U/L, respectively, P = 0.001; AST: 29.8 [15.4] U/L vs 46.0 [16.0] U/L, respectively, P = 0.001; ALP: 154.6 [64.1] U/L vs 211.5 [70.4] U/L, respectively, P= 0.011; and GGT: 49.8 [38.5] U/L vs 64.7 [54.4] U/L, respectively, P = 0.002), as well as in total cholesterol level (176.2 [42.0] mg/dL vs 199.6 [60.6] mg/dL; P = 0.02). Posttreatment liver biopsy was available in 13 patients (81%). Significant improvements in the mean (SD) scores of steatosis (1.46 [0.66] vs 2.43 [0.62]; P = 0.002) and necroinflammatory grade (0.84 [0.24] vs 1.31 [0.51]; P= 0.006) were observed at 6 months compared with baseline, respectively. However, no significant change was noted in the mean (SD) score of fibrosis stage (0.77 [0.33] vs 1.12 [0.59], respectively). None of the patients reported any adverse effects.

Conclusion

In this small, 6-month, open-label study, vitamin E treatment was safe and well tolerated and led to potential biochemical and histologic improvements (except in fibrosis) in patients with NASH.     

弹性酶治疗高脂血症性非酒精性脂肪性肝病的临床观察

目的观察弹性酶肠溶片治疗高脂血症性非酒精性脂肪性肝病的有效性、安全性及耐受性,为临床应用提供依据.方法将76例高脂血症性非酒精性脂肪性肝病患者,随机分为弹性酶组（n=44）,口服弹性酶肠溶片（300 IU/粒）,每次2粒,每日3次,疗程60天,安慰剂组（n=32）,口服安慰剂（淀粉）,剂量及疗程相同;治疗前、治疗30天、60天分别检测肝、肾功能、血脂,并B超随访.结果 6例患者治疗中失访,70例患者纳入疗效统计.弹性酶组总有效率为85%（34/40）,安慰剂组总有效率为20%（6/30）,两组比较差异有统计学意义（P=0.000）;弹性酶组肝功能、血脂明显改善,两组比较差异有统计学意义（P《0.05）;弹性酶对肾功能无明显毒副作用.结论弹性酶肠溶片具有改善肝功能、降低血脂、防治高脂血症性非酒精性脂肪性肝病的作用.     

3种饮食诱导的非酒精性脂肪性肝炎小鼠模型表型比较

目的：本研究旨在比较三种饮食诱导的非酒精性脂肪性肝炎（NASH）小鼠模型的特征，从而为NASH的机制研究和药物开发提供参考。方法：分别用高脂饮食（HFD）喂养小鼠24周、Amylin饮食喂养24周，或高脂-蛋氨酸胆碱缺乏（HFMCD）饮食喂养10周以诱导NASH的表型，并用正常饮食（CD）作为对照。喂养结束后分别检测其体重、肝重、肝脏损伤指标血清转氨酶、肝脏脂质沉积指标甘油三酯、肝纤维化指标羟脯氨酸，用空腹血糖和胰岛素耐量试验（ITT）反映胰岛素敏感性，并对肝组织切片进行HE和天狼星红染色以观察其组织学变化。结果：HFD能导致明显的肥胖和胰岛素抵抗，但诱导出的血清转氨酶升高、肝脏甘油三酯、羟脯氨酸沉积和肝脏组织炎症病变却较轻微或不显著；Amylin饮食能诱导出明显的肥胖、胰岛素抵抗、血清转氨酶升高、肝脏甘油三酯、羟脯氨酸沉积，以及严重的NASH肝脏组织病理学改变；HFMCD饮食能在短时间内诱导出较严重的血清转氨酶上升、肝脏甘油三酯、羟脯氨酸沉积和肝脏病理学改变，但小鼠缺乏胰岛素抵抗和肥胖。结论：三种饮食诱导的小鼠模型各有其特点。总体上，Amylin饮食的NASH模型更能反映人的NASH发生发展过程中的主要特点。     

Need for liver biopsy in pediatric nonalcoholic steatohepatitis diagnosis regardless of improvement in liver damage through weight loss

Liver biopsy is recommended for obese children with fatty liver disease to ensure that nonalcoholic steatohepatitis (NASH) is not overlooked. Even in pediatric cases, regardless of the improvement in liver damage through weight loss, children should be tested and treated with the possibility of NASH in mind.     

Effect of tocotrienol on the primary progression of nonalcoholic steatohepatitis in a mouse model

Tocotrienol (T3), a vitamin E (Vit E) isoform, is known to have both biological and antioxidant effects. Although alpha-tocopherol (α-Toc), another isoform of Vit E is suggested to be a useful treatment against nonalcoholic steatohepatitis (NASH), the effect of T3 on NASH is unclear. This study aimed to comparatively evaluate the effects of T3 and α-Toc on NASH in the early stage of NASH progression, using a recently established NASH mouse model induced by a choline-deficient l-amino acid-defined high-fat diet (CDAHFD). Six-week-old male mice were divided into four groups (n = 6 per group) and fed the CDAHFD for 1 week. The first group was given no other treatment (Pre). The other three groups continued the CDAHFD plus daily oral administration of Vit E-free corn oil (Control), corn oil containing α-Toc, or corn oil containing T3 for additional 2 weeks. Neither Vit E treatment changed the histologic features of NASH, but T3 significantly reduced the mRNA expression of several genes related to inflammation and fibrosis and α-Toc did not. These results suggested that oral T3 treatment was more effective than α-Toc at suppressing hepatic inflammation and fibrosis in the early stage of NASH progression in CDAHFD model mice.     

聚焦解决模式在非酒精性脂肪性肝炎患者健康教育管理中的应用

目的：探讨聚焦解决模式在非酒精性脂肪性肝炎患者健康教育管理中的应用效果。方法选择非酒精性脂肪性肝炎（ NASH）患者60例,按随机数字表法分为对照组和观察组,每组30例。对照组按照常规内容和模式进行健康教育,观察组按照聚焦解决模式5个步骤进行健康教育。比较两组患者健康知识的掌握程度、对护理满意度、生活质量水平和出院后6个月治疗依从性。结果出院时聚焦解决模式组NASH健康知识掌握达到优的患者占90．0％,对照组占33．3％,差异有统计学意义（χ2＝9．863,P＜0．05）±观察组护理满意度为93．3％,高于对照组的83．3％,差异有统计学意义（χ2＝1．254, P＜0．05）±观察组患者生活质量综合评定问卷（GQOLI-74）总分（238．3±24．68）分,高于对照组的（201．53±21．59）分,差异有统计学意义（t＝7．568,P＜0．05）。出院后6个月观察组治疗完全依从患者占86．6％,对照组占66．7％,差异有统计学意义（χ2＝6．436,P＜0．05）。结论采用聚焦解决模式对NASH患者的治疗有明显的指导作用,可改善患者的生活质量和满意度,提高患者依从性。     

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.     

瘦素和转化生长因子β_1对非酒精性脂肪性肝炎患者肝纤维化的促进作用研究

目的针对非酒精性脂肪性肝炎（NASH）患者体内转化生长因子β1（TGF-β1）和瘦素与肝纤维化之间的相关性进行研究,从而阐述两者对肝纤维化的促进作用。方法检测NASH患者血清瘦素水平以及TGF-β1水平,同时检测NASH患者的血清肝纤维化指标透明质酸（HA）、板层素（LN）、Ⅲ型前胶原肽（PCⅢ）等,其结果与单纯性脂肪肝患者及健康对照者进行组间比较,最后对血清瘦素、TGF-β1与肝纤维化指标进行相关性分析。结果 NASH患者血清瘦素水平以及TGF-β1水平明显高于对照组,差异有显著性,并且NASH患者血清瘦素水平、TGF-β1水平以及肝纤维化指标之间呈正相关。结论瘦素和TGF-β1是NASH进展为肝纤维化过程中的重要因子,但其分子机制需进一步深入研究。