门冬氨酸鸟氨酸联合易善复治疗非酒精性脂肪性肝炎临床观察

目的观察门冬氨酸鸟氨酸联合易善复对非酒精性脂肪性肝炎的临床疗效。方法非酒精性脂肪性肝炎患者70例,随机分成两组,治疗组采用门冬氨酸鸟氨酸静脉给药(剂量为10 g/次,1次/d)联合易善复口服治疗(456 mg/次,3次/d),对照组仅采用易善复治疗(用法用量同治疗组),于治疗前及治疗4周后观察患者血清谷丙转氨酶、谷草转氨酶、甘油三酯、胆固醇变化,4周后B超观察肝脏形态变化。结果两组患者于治疗前后实验室指标均有明显改善,但治疗组明显优于对照组(P<0.05);4周后治疗组肝脏声像形态评分要明显优于对照组(P<0.05)。结论门冬氨酸鸟氨酸联合易善复治疗非酒精性脂肪性肝炎具有较好的临床疗效,值得进一步研究。     

复方二氯醋酸二异丙胺联合门冬氨酸鸟氨酸治疗老年性非酒精性脂肪性肝炎的效果研究

目的 探讨复方二氯醋酸二异丙胺联合门冬氨酸鸟氨酸治疗老年性非酒精性脂肪性肝炎(NASH)的效果。方法 选取2019年1月至2019年12月于四川省林业中心医院治疗住院的老年性NASH患者95例,根据随机数表法分为对照组与观察组,每组各46例。对照组给予阿托伐他汀治疗,观察组在对照组的基础上给予复方二氯醋酸二异丙胺联合门冬氨酸鸟氨酸进行治疗。比较2组患者的肝功能指标、血脂指标、超声影像学评分、非酒精性脂肪性肝病活动度积分(NAS)、炎性因子及不良反应发生情况。采用SPSS 26.0统计学软件进行数据分析。根据数据类型,组间比较采用独立样本t检验或χ²检验。结果 与对照组相比,治疗后观察组肝功能指标丙氨酸氨基转移酶[(53.29±6.84)和(65.73±7.25)U/L]、天门冬氨酸氨基转移酶[(34.61±4.27)和(45.73±5.12)U/L]及γ-谷氨酰转移酶 [(41.25±3.59)和(64.74±5.52)U/L] 显著降低(均P＜0.05),血脂指标总胆固醇[(4.12±0.64)和(4.87±0.66)mmol/L]、甘油三酯[(1.42±0.31)和(1.63±0.42)mmol/L]及低密度脂蛋白胆固醇[(2.27±0.61)和(3.04±0.59)mmol/L]显著降低(均P＜0.05),超声影像学评分[(6.18±1.34)和(7.25±1.46)分]及NAS积分[(3.27±0.54)和(3.85±0.73)分]显著降低(均P＜0.05),血清中白细胞介素-6 [(109.43±11.87)和(129.75±10.96)μg/L]、肿瘤坏死因子-α[(51.26±6.05)和(63.18±6.72)μg/L]及转化生长因子-β[(6.03±1.92)和(8.45±2.21)μg/L]显著降低(均P＜0.05)。2组患者不良反应发生率比较,差异无统计学意义(P＞0.05)。结论 复方二氯醋酸二异丙胺联合门冬氨酸鸟氨酸辅助治疗老年性NASH的效果显著,具有一定的临床应用价值。     

门冬氨酸鸟氨酸对非酒精性脂肪性肝炎合并肌少症性肥胖小鼠的保护作用

目的 探讨应用门冬氨酸鸟氨酸对非酒精性脂肪性肝炎(NASH)和肌少症性肥胖小鼠的干预作用.方法 将28只雄性C57B/b小鼠随机分为对照组11只和模型组17只,分别给予普通饮食和高脂饮食饲养,在12周末将两组小鼠各随机处死5只以验证NASH模型.将其余模型组小鼠随机分为模型对照组6只和干预组6只,给予等量生理盐水或门冬...     

门冬氨酸-鸟氨酸治疗黄疸型慢性病毒性肝炎的临床疗效观察

目的评价门冬氨酸-鸟氨酸治疗黄疸型慢性病毒性肝炎的临床疗效。方法将108例黄疸型慢性病毒性肝炎患者随机分为3组,分别接受4周的门冬氨酸-鸟氨酸、腺苷蛋氨酸和门冬氨酸钾镁等治疗,并检测患者治疗前后的血清总胆红素。结果门冬氨酸-鸟氨酸和腺苷蛋氨酸组在4周治疗结束时降低血清总胆红素的有效率分别为75.0%和72.2%,显著高于门冬氨酸钾镁组（30.6%）,P〈0.01;门冬氨酸-鸟氨酸与腺苷蛋氨酸组患者血清总胆红素每日降幅分别为4.3μmol/L±5.1μmol/L和4.3μmol/L±5.6μmol/L,显著高于门冬氨酸钾镁对照组（2.1μmol/L±8.3μmol/L）,P〈0.01。结论注射用门冬氨酸-鸟氨酸粉针剂能有效降低黄疸型慢性病毒性肝炎患者的血清总胆红素水平。     

非酒精性脂肪性肝炎的治疗

非酒精性脂肪肝可以是一个独立的疾病 ,但更多见于全身性疾患在肝脏的病理过程。肥胖症、药物和毒物中毒、营养不良、糖尿病、妊娠、肝炎病毒或其他病原体感染以及先天性代谢缺陷等都可引起非酒精性脂肪肝。·本病在组织学上有与酒精性肝病类似的表现 ,肝活检显示从轻度的脂肪性肝炎至重度肝纤维化和肝硬化不同的组织学特征。·非酒精脂肪性肝炎诊断一般依据Ｐｏｗｅｌｌ等建议的标准 ,即①肝活检标本显示伴有炎症的中～重度大泡性脂肪变性 ,可伴或不伴有Ｍａｌｌｏｒｙ小体、纤维化或肝硬化 ;②无饮酒史或饮酒每周 <4 0克 ,随机检测血乙醇…     

非酒精性脂肪性肝炎的药物治疗

非酒精性脂肪性肝炎是非酒精性脂肪性肝病的一种,其可以进一步发展为终末期肝病以致肝功能衰竭。非酒精性脂肪性肝炎药物治疗主要包括二甲双胍、过氧化物酶体增殖物-γ激动剂、已酮可可碱、N-乙酰半胱氨酸、血管紧张素Ⅱ受体拮抗剂、熊去氧胆酸、维生素E、降脂药等。近年来,对这些药物治疗非酒精性脂肪性肝炎的疗效也做了相关研究,但均未得出确切的结论。     

门冬氨酸鸟氨酸治疗酒精性肝病的临床疗效评价

目的探讨门冬氨酸鸟氨酸治疗酒精性肝病的临床疗效。方法将200例酒精性肝病其中脂肪肝140例,酒精性肝炎60例病人随机分为治疗组和对照组,治疗组用门冬氨酸鸟氨酸5.0g/天,对照组用肝安注射液,连用30天,比较两组治疗前后总胆红素、谷丙转氨酶、谷草转氨酶、血清白蛋白、血清球蛋白的水平。结果疗程结束时,治疗组的TBIL、ALT、AST、ALB、及GLB水平与治疗前比均有明显好转(P<0.05);并且治疗组治疗后ALT及AST水平明显低于对照组(P<0.05)。结论门冬氨酸鸟氨酸对酒精性肝病有较好的临床治疗效果。     

中西医治疗非酒精性脂肪性肝炎的研究进展

非酒精性脂肪性肝炎(NASH)是非酒精性脂肪性肝病(NAFLD)的一种严重类型[1],系排除酒精及其他明确的肝损害因素外,其他因素(包括Ⅱ型糖尿病、高脂血症、高血压等)引起的以肝细胞脂质累积和变性、炎症反应、肝细胞损害、不同程度纤维化为特征的临床综合征[2]。近年来NASH发病率不断攀升,以2016年数据为例,中国的NASH病例为3261万,相关建模预计2030年发病率将增长48%,达到4826万[3]。NASH会进一步引发肝纤维化、肝硬化及肝细胞癌等,已成为全球亟待解决的重要问题之一。NASH的发病机制尚未完全明确,治疗以保肝、减脂、改善糖代谢为主,维生素E和肠道菌群的研究正在兴起。而中医药从疏肝理气、清热利湿、活血化瘀以及补气健脾等方面对该病辨证施治,取得较好疗效。笔者将近年来西医、中医、中西医结合治疗NASH的研究进展以综述形式进行总结、探讨。     

非酒精性脂肪性肝炎

非酒精性脂肪性肝炎具有与酒精性肝炎相似的组织学表现，但具有不同的发病机制和预后，本就这两方面作一综述。     

二氯醋酸二异丙胺治疗非酒精性脂肪性肝病的随机双盲临床研究

目的 研究二氯醋酸二异丙胺治疗非酒精性脂肪性肝病的临床疗效和安全性。方法 用随机双盲多中心剂量半行对照的临床试验设计选择非酒精性脂肪性肝病患者，分别用二氯醋酸二异丙胺高剂量(120mg／d)和低剂量(60mg／d)治疗8周，观察其疗效和安全性。结果 本试验共有l27例患者人选，高剂量组63例，低剂量组64例。术见脱落病例，剔除4例，剔除率3．1％，实际完成病例数l23例，高剂量组6l例，低剂量组62例。治疗后8周高剂量组和低剂量组临缶床疗效总有效率分别为87．8％和79．6‰(P=0．2536)，内氨酸氨基转移酶复常总有效率分别为55．7％和69．4％(P=0．0807)，血脂总有效率分别为67．2％和67．7％(P=O．9320)，B超脂肪肝影像学榆查总有效率分别为51．7％和43．5％(P=O．2879)，两组比较，差异均尢统计学意义。两组患者中各有1例发生不良反应，高和低剂量组的发生率分别为1．6％和1．6％，表现为口干，未见严重的不良反应。结论 二氯醋酸二异丙胺可安全有效地用于治疗非酒精性脂肪性肝病。     

大黄酸对大鼠非酒精性脂肪性肝炎的影响

非酒精性脂肪肝炎（NASH）是一种常见的肝病，可进展为终末期肝硬化。NASH目前缺乏有效的治疗手段。近年来，研究发现大黄酸具有广泛的药理作用，对NASH可能有治疗作用。但有关大黄酸对大鼠NASH防治作用的研究鲜见报道。[第一段]     

疏肝消脂颗粒剂治疗非酒精性脂肪性肝炎的临床疗效观察

目的：观察疏肝消脂颗粒剂治疗非酒精性脂肪性肝炎的临床疗效.方法：选择非酒精性脂肪性肝炎患者120例,随机分为治疗组（60例）,对照组（60例）,其中治疗组用疏肝消脂颗粒剂冲服,对照组用多烯磷脂酰胆碱胶囊治疗.两组患者治疗3个月,分别观察其临床症状和体征、肝功能、血脂等指标的变化情况.结果：两组患者临床症状皆能改善,治疗组疗效优于对照组;在改善肝功能、血脂方面,两组患者治疗后均较治疗前有明显改善,差异均有显著性意义（P＜0.05）,治疗组疗效优于对照组,差异有显著性意义（P＜0.05）.结论：疏肝消脂颗粒剂治疗非酒精性脂肪性肝炎的临床疗效确切,可改善患者临床症状和体征、降低肝功能及血脂指标,其疗效优于多烯磷脂酰胆碱胶囊.     

Progressive fibrosis in nonalcoholic steatohepatitis: association with altered regeneration and a ductular reaction

BACKGROUND & AIMS: Portal fibrosis and linkage is a key feature of progressive disease in nonalcoholic steatohepatitis (NASH), but not simple steatosis. It is underappreciated and poorly understood. Fatty liver has impaired regeneration that induces a secondary replicative pathway using bipotential, periportal, hepatic progenitor cells (HPCs). We propose that activation of this pathway, with increased cell injury in NASH, also induces a periportal ductular reaction (DR) that could produce a profibrogenic stimulus. METHODS: Biopsy specimens from 107 patients with nonalcoholic fatty liver disease and 11 controls were immunostained with cytokeratin-7 to quantify the DR and HPCs, and with p21 to assess hepatocyte replicative arrest. These results were correlated with clinicopathologic variables. RESULTS: Patients with nonalcoholic fatty liver disease had expansion of HPCs, with a strong association between HPCs and the DR (r(s) = 0.582, P < .0001). In those with NASH (n = 69) there was an increased DR compared with simple steatosis, which correlated with the stage of fibrosis (r(s) = 0.510, P < .0001). The DR increased with the grade of NASH activity (r(s) = 0.478, P < .0001), grade of portal inflammation (r(s) = 0.445, P < .0001), and extent of hepatocyte replicative arrest (r(s) = 0.446, P < .0001). Replicative arrest was in turn associated with insulin resistance (r(s) = 0.450, P < .0001) and NASH activity (r(s) = 0.452, P < .0001). By multivariate analysis, the extent of DR (odds ratio [OR] = 17.9, P = .016), hepatocyte ballooning (OR = 8.1, P < .0001), and portal inflammation (OR = 3.3, P = .005) were associated independently with fibrosis. CONCLUSIONS: These findings suggest that an altered replication pathway in active NASH promotes a periportal DR, which in turn may provoke progressive periportal fibrogenesis.     

Diagnosis and therapy of nonalcoholic steatohepatitis

The increasing prevalence of obesity, insulin resistance, and the metabolic syndrome has significant implications for the future of chronic liver disease. The resultant increase in the number of patients with nonalcoholic fatty liver disease (NAFLD) is expected to translate into increased numbers of patients with end-stage liver disease (cirrhosis), liver failure, and hepatocellular carcinoma. It is particularly important to identify the patients who are at greatest risk of these aforementioned complications of chronic liver disease, those nonalcoholic fatty liver disease patients with nonalcoholic steatohepatitis. Currently liver biopsy is the gold standard for diagnosis, but less invasive, highly accurate, and affordable screening tools are required. These tools may include radiologic or laboratory studies to identify patients noninvasively who may benefit from therapeutic interventions. Clinical scoring systems that may be used in general practice as initial screening tools also may prove useful. Most therapeutic modalities available or under development target the major pathways thought essential in the pathogenesis of nonalcoholic steatohepatitis and often are directed at reducing body mass index and improving insulin resistance via pharmacologic, surgical, dietary, or exercise regimens. Other potential therapeutic agents directed at cytoprotection or reduction of fibrosis are under investigation. This article focuses on diagnosis and therapy available and under development for this chronic liver disease.     

Treatment of nonalcoholic steatohepatitis with colestimide

Aim: To clarify the usefulness of colestimide in patients with nonalcoholic steatohepatitis (NASH) with hyperlipidemia. Methods: In an open‐label randomized controlled trial, 17 NASH patients with hyperlipidemia received colestimide (3 g/day) for 24 weeks. There were 21 control patients. All patients received lifestyle modification therapy. Efficacy was assessed based on metabolic profile, insulin resistance, transaminases, serum hepatic fibrosis markers, adipokine levels, visceral fat on computed tomography (CT), and the fatty liver grade on CT. NASH patients with moderate to severe steatosis by histology were also evaluated separately. Results: Baseline clinical characteristics of the two groups were similar. Both groups experienced a significant decrease of BMI with no difference between them. However, visceral fat decreased significantly more in the colestimide group (P = 0.046). Aspartate aminotransferase (AST) showed a significantly greater decrease in the colestimide group compared with the control group (P = 0.042). In patients with moderate to severe histological steatosis, there were significant differences between the two groups regard to HbA_1c, transaminases, and hyaluronic acid (P = 0.018 for HbA_1c, P = 0.003 for AST, P = 0.042 for alanine aminotransferase, and P = 0.042 for hyaluronic acid). Steatosis significantly improved in patients in the colestimide group who had fatty liver on CT (P = 0.049). In the colestimide group, abdominal distension and/or constipation were seen, but mostly tolerable, no other clinical or laboratory adverse events associated with the use of this medicine were not observed. Conclusions: Colestimide seems to increase the efficacy of lifestyle modification in NASH patients with hyperlipidemia. Its beneficial effects were more prominent in NASH patients with moderate to severe histological steatosis.     

水飞蓟宾治疗非酒精性脂肪性肝炎临床疗效观察

目的评价水飞蓟宾胶囊治疗非酒精性脂肪性肝炎（NASH）的临床疗效。方法非酒精性脂肪性肝炎患者72例,随机分为两组。治疗组40例给予水飞蓟宾治疗,对照组32例服用护肝片治疗,疗程均为12周。测定治疗前后两组患者血清酶学、血脂及腹部超声变化,并记录患者临床症状。结果治疗后两组临床症状、血清酶学、血脂及脂肪肝程度差异均有统计学意义,未发现明显不良反应。结论水飞蓟宾胶囊治疗NASH可改善患者临床症状,降低血清转氨酶及血脂,减轻肝内脂肪沉积,具有显著疗效且用药安全。     

Hepatocyte apoptosis and fas expression are prominent features of human nonalcoholic steatohepatitis

BACKGROUND & AIMS: The pathogenesis of nonalcoholic steatohepatitis (NASH) remains poorly understood. Although apoptosis is a common mechanism of liver injury, the extent and clinical significance of apoptosis in NASH has not been examined. Thus, the aims of this study were to quantify hepatocyte apoptosis in NASH, correlate it with disease severity, and identify possible mechanisms of apoptosis induction. METHODS: Hepatocyte apoptosis was assessed in NASH, simple steatosis, alcoholic hepatitis, and controls without liver disease using the TUNEL assay and immunohistochemistry for activated caspases 3 and 7. Liver specimens were also graded according to the magnitude of inflammation and fibrosis. RESULTS: TUNEL-positive cells were significantly increased in liver biopsy specimens from patients with NASH compared with simple steatosis and controls. Unexpectedly, TUNEL-positive cells were also greater in NASH vs. alcoholic hepatitis. Immunohistochemistry demonstrated active caspases 3 and 7 in NASH specimens, confirming the occurrence of apoptosis in this disease. A positive correlation was observed between hepatocyte apoptosis and hepatic fibrosis and inflammatory activity, respectively. The Fas receptor was strongly expressed in hepatocytes in liver specimens from NASH patients as compared with controls. CONCLUSIONS: Hepatocyte apoptosis is significantly increased in patients with NASH and correlates with disease severity, suggesting that antiapoptotic therapy may be useful in this syndrome.     

左卡尼汀联合多烯磷脂酰胆碱治疗非酒精性脂肪性肝炎的疗效观察

目的评价左卡尼汀联合多烯磷脂酰胆碱治疗非酒精性脂肪性肝炎的疗效。方法将82例非酒精性脂肪性肝炎患者随机分为两组,试验组41例联合服用左卡尼汀联合多烯磷脂酰胆碱,对照组41例单用多烯磷脂酰胆碱为对照组。疗程均为12周。治疗前后测定血清转氨酶、血脂水平及肝/脾CT比值。结果治疗后试验组血清转氨酶、血脂下降明显,肝/脾CT比值升高显著,与对照组比较差异有统计学意义（P〈0.05）。结论左卡尼汀联合多烯磷脂酰胆碱治疗非酒精性脂肪性肝炎具有良好的效果,值得临床应用。