熊去氧胆酸治疗婴儿胆汁淤积症疗效观察

目的 观察熊去氧胆酸(UDCA)口服治疗婴儿胆汁淤积症的临床疗效.方法 将72例1～6月婴儿胆汁淤积症患儿随机分为观察组和对照组,各36例.两组都进行常规护肝治疗,观察组在常规护肝治疗基础上增加熊去氧胆酸口服,对两组治疗前后症状体征和肝生化指标的改善程度进行比较,并对延长服药时间疗效的变化进行观察.结果 观察组服药1周总有效率为58.33％,对照组总有效率为38.89％,两组疗效比较,差异有统计学意义(P＜0.05);服药2周观察组总有效率为86.11％,对照组总有效率为52.78％,治疗后两组疗效比较,差异有统计学意义(P＜0.01),观察期间两组未见明显不良反应.结论 熊去氧胆酸口服治疗婴儿胆汁淤积症疗效好,副作用少,可以在临床上推广使用.     

熊去氧胆酸与羟甲烟胺治疗慢性乙型肝炎肝内胆汁淤积的疗效比较

目的:比较熊去氧胆酸与羟甲烟胺治疗慢性乙型肝炎肝内胆汁淤积的疗效。方法:将96例慢性乙型肝炎肝内胆汁淤积患者随机分为熊去氧胆酸组(56例)和羟甲烟胺组(40例),2组在抗病毒和护肝治疗的基础上分别加用熊去氧胆酸与羟甲烟胺治疗,疗程均为4周。分别比较2组治疗2、4周后的临床疗效。结果:治疗2周时,2组患者肝功能观察指标均有明显改善,但熊去氧胆酸组降低总胆红素、直接胆红素、碱性磷酸脂酶的幅度与羟甲烟胺组比较无显著性差异(P>0.05);治疗4周时,熊去氧胆酸组血清总胆红素、直接胆红素、碱性磷酸脂酶降幅较羟甲烟胺组高,差异有统计学意义(P<0.05)。熊去氧胆酸组总有效率优于羟甲烟胺组(75%vs.70%,P=0.02)。结论:熊去氧胆酸治疗慢性乙型肝炎肝内胆汁淤积的疗效优于羟甲烟胺。     

腺苷蛋氨酸联合熊去氧胆酸治疗妊娠期胆汁淤积的临床疗效

目的评价腺苷蛋氨酸联合熊去氧胆酸治疗妊娠期胆汁淤积的临床疗效。方法选取2011年9月至2013年1月我院收治的妊娠期胆汁淤积患者65例,随机分为两组。观察组33例,在常规治疗基础上选用腺苷蛋氨酸联合熊去氧胆酸进行治疗;对照组32例,在常规治疗基础上仅应用熊去氧胆酸,观察并比较两组患者皮肤瘙痒症状改善情况、生化指标变化以及妊娠结局。结果观察组皮肤瘙痒症状改善明显优于对照组,比较差异有统计学意义(P<0.05);观察组总胆红素、天冬氨酸转氨酶和丙氨酸转氨酶的浓度明显下降,与对照组比较差异有统计学意义(P<0.05);观察组妊娠结局明显优于对照组,比较差异有统计学意义(P<0.05)。结论腺苷蛋氨酸联合熊去氧胆酸治疗妊娠期胆汁淤积的临床疗效好,能明显改善患者皮肤瘙痒症状,降低其生化指标并改善妊娠结局,值得在临床上予以推广。     

注射用丁二磺酸腺苷蛋氨酸联合熊去氧胆酸片治疗妊娠期重度肝内胆汁淤积症的效果

目的 观察注射用丁二磺酸腺苷蛋氨酸联合熊去氧胆酸片治疗妊娠期重度肝内胆汁淤积症的临床效果。方法 选取2019年3月—2020年2月长沙市中心医院妇产科收治的妊娠期重度肝内胆汁淤积症患者80例,根据随机数字表法分为观察组和对照组,每组40例。对照组采用熊去氧胆酸片治疗,观察组则在对照组基础上加用注射用丁二磺酸腺苷蛋氨酸治疗,2组均连续治疗2周。比较2组患者治疗效果,治疗前后皮肤瘙痒评分、肝功能指标水平,不良反应和妊娠结局情况。结果 观察组治疗总有效率为97.50%,高于对照组的80.00%(χ²=4.507,P=0.034);治疗2周后,2组患者皮肤瘙痒评分和总胆红素、直接胆红素、天门冬氨酸氨基转移酶水平均较治疗前降低,且观察组低于对照组(P均<0.01);2组患者治疗期间均无明显不良反应;2组患者治疗后的早产、剖宫产与胎儿窘迫、新生儿窒息发生率均低于对照组,差异有统计学意义(P<0.05)。结论 注射用丁二磺酸腺苷蛋氨酸联合熊去氧胆酸片治疗妊娠期重度肝内胆汁淤积症预后效果显著,促进患者瘙痒程度、肝功能改善,进而改善患者的妊娠结局。     

熊去氧胆酸与S-腺苷蛋氨酸治疗妊娠期肝内胆汁淤积症

目的探讨熊去氧胆酸与S-腺苷蛋氨酸联合治疗妊娠期肝内胆汁淤积症(ICP)的疗效及血生化参数变化规律。方法以84例ICP患者为研究对象,给予S-腺甘蛋氨酸静滴1 500 mg/d+熊去氧胆酸250 mg4次/d口服治疗,比较治疗前后的血生化参数。结果治疗后,ICP患者总胆汁酸、甘胆酸、总胆红素、直接胆红素、天门冬氨酸氨基转移酶降低,与治疗前比较,差异有统计学意义(P<0.01)。血浆甘胆酸水平与天门冬氨酸氨基转移酶之间呈低度正相关(r=0.29,P<0.05)。结论 S-腺甘蛋氨酸、熊去氧胆酸治疗ICP疗效良好,血生化参数是对妊娠期肝内胆汁淤积症疗效评价的实用临床指标。     

熊去氧胆酸联合茵栀黄口服液治疗妊娠期肝内胆汁淤积症临床效果评价

目的探讨熊去氧胆酸联合茵栀黄口服液治疗妊娠期肝内胆汁淤积症临床效果评价。方法将我院产科治疗的124例妊娠期肝内胆汁淤积症患者随机分为两组,对照组单用熊去氧胆酸治疗,观察组采用熊去氧胆酸联合茵栀黄口服液治疗,比较两组患者的治疗效果、肝内胆汁淤积各指标、妊娠结局。结果观察组治疗有效率为96.77%,较对照组的75.81%明显提高,差异有统计学意义(P<0.05);观察组治疗后TBA、ALT、AST、TB水平明显低于对照组,差异有统计学意义(P<0.05);观察组早产、剖宫产、胎儿窘迫、产后24h出血量、新生儿体质量等均明显较对照组改善,差异有统计学意义(P<0.05)。结论熊去氧胆酸联合茵栀黄口服液治疗妊娠期肝内胆汁淤积症临床疗效显著,能够明显改善相关生化指标,缓解临床症状,改善妊娠结局,减少对母婴的不良影响,具有积极的临床意义。     

熊去氧胆酸联合腺苷蛋氨酸、前列地尔治疗肝内胆汁淤积的疗效分析

目的 探讨熊去氧胆酸联合腺苷蛋氨酸、前列地尔治疗肝内胆汁淤积的临床疗效.方法 选取我院2016年1月至2016年5月收治的50例肝内胆汁淤积患者为研究对象,将所有患者根据不同的给药方法 分为对照组和研究组,每组25例,对照组患者采用腺苷蛋氨酸与前列地尔联合治疗,研究组患者采用熊去氧胆酸联合腺苷蛋氨酸、前列地尔治疗,观察两组患者临床治疗效果以及治疗前后肝功能变化.结果 研究组治疗总有效率为92.00%(23/25),显著高于对照组的76.00%(19/25),且治疗后研究组患者肝功能各指标水平显著优于对照组,两组比较差异有统计学意义(P<0.05).结论 对肝内胆汁淤积患者采用熊去氧胆酸联合腺苷蛋氨酸、前列地尔能治疗,能有效的改善患者的肝功能,临床疗效显著,值得推广应用.     

熊去氧胆酸联合地塞米松治疗妊娠期肝内胆汁淤积症的疗效观察

目的探讨熊去氧胆酸联合地塞米松治疗妊娠期肝内胆汁淤积症的临床疗效。方法将我院2010年8月至2012年12月间收治的104例妊娠期肝内胆汁淤积症患者随机分为治疗组和对照组,每组各52例,对照组患者给予单纯地塞米松治疗,治疗组患者在此基础上加用熊去氧胆酸治疗,比较两组患者的临床疗效。结果两组患者治疗后的ALT、AST及TBA水平较治疗前均有显著改善,差异有统计学意义(P<0.05),治疗组患者各项指标改善情况优于对照组患者,组间差异有统计学意义(P<0.05)。结论采用熊去氧胆酸联合地塞米松治疗妊娠期肝内胆汁淤积症临床疗效确切,能够显著改善患者的临床症状,保证母婴安全,值得临床进一步推广使用。     

丁二磺酸腺苷蛋氨酸联合熊去氧胆酸治疗妊娠期肝内胆汁淤积症40例

目的：探讨丁二磺酸腺苷蛋氨酸联合熊去氧胆酸治疗妊娠期肝内胆汁淤积症的疗效和安全性.方法：80例妊娠期肝内胆汁淤积症患者随机分为对照组和观察组各40例.对照组在常规治疗基础上加用熊去氧胆酸0.25 g,po,bid;观察组在对照组基础上再加用丁二磺酸腺苷蛋氨酸1.0g,po,bid.两组疗程均为7d.对比两组患者的临床瘙痒症状、肝功能血清标记物水平、围产结局及新生儿健康程度.结果：观察组瘙痒的Riikonen评分改善程度优于对照组（P＜0.05）;治疗后,两组患者的各项肝功能指标如TB、ALT、AST等均有显著下降,观察组下降程度显著高于对照组（P＜0.05）;观察组患者新生儿窒息发生率和产后出血发生率的差异明显低于对照组（P＜0.05或0.01）.结论：丁二磺酸腺苷蛋氨酸联合熊去氧胆酸治疗妊娠期肝内胆汁淤积症安全性高、疗效确切.     

熊去氧胆酸治疗妊娠期肝内胆汁淤积症(ICP)临床疗效及安全性分析

目的:观察熊去氧胆酸治疗妊娠期肝内胆汁淤积症(ICP)的临床疗效及安全性分析。方法:选取在我院胆汁淤积症的妊娠期妇女患者100例,并随机分成治疗组和对照组,每组50例。治疗组采用口服熊去氧胆酸治疗;对照组给予静脉滴注能量合剂治疗,两组均以10d为一疗程,比较临床疗效和安全性。结果:治疗组的血生化指标改善明显优于对照组,差异具有统计学意义,P<0.05。治疗组围产儿结局明显优于对照组,差异具有统计学意义,P<0.05。结论:本次实验结果表明熊去氧胆酸治疗妊娠期胆汁淤积症有较显著的治疗作用,并且不良反应较小,安全性较高,临床应用价值较大。     

The therapeutic effects of ursodeoxycholic acid as an anti-apoptotic agent

The dihydroxy bile acid, ursodeoxycholic acid (UDCA), has been in widespread clinical use in the Western world since the mid 1980s, when it was initially used for gallstone dissolution [1,2] and subsequently for the treatment of chronic cholestatic liver diseases [3,4]. Many clinical trials of UDCA in a variety of cholestatic disorders established biochemical and clinical improvements, and most importantly showed a significant prolongation of transplant-free survival after four years of treatment with UDCA in patients with primary biliary cirrhosis [5]. Despite its clinical efficacy, the precise mechanism(s) by which UDCA improves liver function during cholestasis is still a matter of debate [6]. It was initially considered that the choleretic effect of UDCA, coupled with its ability to cause a marked shift in the composition of the bile acid pool towards hydrophilicity, accounted for its mechanism of action. In recent years, however, it has become evident that UDCA and its conjugated derivatives are capable of exerting direct effects at the cellular, subcellular, and molecular levels by stabilising cell membranes, affecting signal transduction pathways, and regulating immune responses. In addition, we have shown that UDCA plays a unique role in modulating the apoptotic threshold in both hepatic and non-hepatic cells [7-10]. The purpose of this article is to examine the mechanism(s) by which UDCA prevents apoptotic cell death associated with cholestasis. In addition, we will also review a potentially novel and, heretofore, unrecognised role of UDCA as a therapeutic agent in the treatment of non-liver diseases associated with increased levels of apoptosis as a pathogenesis of the disorder.     

熊去氧胆酸治疗妊娠肝内胆汁淤积症17例

目的：评价熊去氧胆酸(UDCA)治疗妊娠期肝内胆汁淤积症(ICP)的效果。方法：38例患者，随机分成两组。治疗组17例，采用UDCA 100 mg，po，tid。对照组21例，给予10%葡萄糖注射液500 mL，维生素C 3 g，肌苷0.4 g，静脉滴注，两组均以14 d为1个疗程，观察疗效。结果：治疗组瘙痒评分治疗1周后明显下降，血丙氨酸氨基转移酶(ALT)和血清总胆汁酸(TBA)明显下降(P＜0.05)，而对照组无明显改变(P＞0.05)；与对照组相比，治疗组早产、胎儿窒息、羊水粪染发生明显减少(P＜0.05)。结论：UDCA是治疗ICP安全、有效的药物。     

Early treatment with ursodeoxycholic acid for cholestasis in children on parenteral nutrition because of primary intestinal failure

BACKGROUND: There is conflicting evidence as to whether ursodeoxycholic acid (UDCA) reduces the incidence of parenteral nutrition-associated cholestasis. AIM: To investigate the efficacy of UDCA on parenteral nutrition-associated cholestasis in children with intestinal failure due to short bowel syndrome or to other causes. METHODS: Children with cholestasis received 30 mg/kg/day UDCA. Improvement or normalization of parenteral nutrition-associated cholestasis was evaluated at 6 months of therapy and at the last follow-up. In a subgroup of children, serum UDCA levels were measured while receiving UDCA and after 4 weeks withdrawal. RESULTS: Twelve children were treated with UDCA. Full remission or partial improvement of parenteral nutrition-associated cholestasis occurred in 11 of 12 children. In three of four children, withdrawal of UDCA was associated with a rebound rise of cholestasis. Only one of 12 treated children showed no improvement and in this patient, in contrast to four other patients, plasma levels of UDCA did not increase during treatment.CONCLUSIONS: Ursodeoxycholic acid was effective in controlling parenteral nutrition-associated cholestasis. The efficacy of UDCA also in children with short bowel is related to intestinal absorption.     

High-performance liquid chromatographic determination of ursodeoxycholic acid after solid phase extraction of blood serum and detection-oriented derivatization

Ursodeoxycholic acid (3, 7β-dihydroxy-5β-cholanoic acid, UDCA) is a therapeutically applicable bile acid widely used for the dissolution of cholesterol-rich gallstones and in the treatment of chronic liver diseases associated with cholestasis. UDCA is more hydrophilic and less toxic than another therapeutically valuable bile acid, chenodeoxycholic acid (CDCA), the 7-epimer of UDCA. Procedures for sample preparation and HPLC determination of UDCA in blood serum were developed and validated. A higher homologue of UDCA containing an additional methylene group in the side chain was synthetized and used as an internal standard (IS). Serum samples with IS were diluted with a buffer (pH=7). The bile acids and IS were captured using solid phase extraction (C18 cartridges). The carboxylic group of the analytes was derivatized using 2-bromo-2′-acetonaphthone (a detection-oriented derivatization), and reaction mixtures were analyzed (HPLC with UV 245 nm detection; a 125–4 mm column containing Lichrospher 100 C18, 5 μm; mobile phase: acetonitrile–water, 6:4 (v/v)). Following validation, this method was used for pharmacokinetic studies of UDCA in humans.     

S-腺苷蛋氨酸联合熊去氧胆酸治疗妊娠期肝内胆汁淤积症的疗效观察

目的观察思美泰联合熊去氧胆酸治疗妊娠期肝内胆汁淤积症（intrahepatic cholestasis of pregnancy．ICP）的疗效。方法选择60例ICP患者．随机分为观察组（30例）和对照组（30例）两组。观察组联用思美泰与熊去氧胆酸治疗10d,对照组单用熊去氧胆酸治疗10d。治疗前后分别检测两组患者血清总胆酸（TBA）、总胆红素（TB）、谷丙转氨酶（ALT）和谷草转氮酶（AST）,并进行瘙痒评分;评价两组患者妊娠结局。结果两组患者治疗无瘙痒评分、TBA、TB、ALT、AST的水平均较治疗前降低（P〈0．01）;观察组治疗后瘙痒评分、TBA、TB、ALT、AST的水平较对照组下降明显,差异有显著性意义（P〈0．05）。妊娠结局：两组羊水污染率、早产率、新生儿窒息率及新生儿体重差异有境计学意义（P〈0．01）。结论思美泰联合熊去氧胆酸是治疗ICP安全有效方法．可改善妊娠预后。     

Effect of ursodeoxycholic acid administration in patients with acute viral hepatitis: a pilot study

BACKGROUND: Ursodeoxycholic acid (UDCA) is able to improve biochemical markers of cholestasis, with a parallel decrease in transaminases, in various cholestatic liver diseases. AIM: To evaluate the effects of UDCA administration on acute viral hepatitis-related cholestasis and the course of acute viral hepatitis. METHODS: Seventy-nine consecutive patients with acute viral hepatitis (HBV: 43, HCV: 11, HAV: 15, HEV: 3, Non A-E: 7) were randomized to receive either UDCA for 3 weeks or no treatment. Liver biochemistry and serum bile acid determinations were run at weekly intervals. RESULTS: No significant differences were observed in mean percentage decreases in transaminases between treated and untreated patients. By contrast, cholestatic indexes decreased significantly more quickly in patients treated with UDCA than in controls, and this effect was more evident in patients with increasing alanine transaminase levels at admission. After a peak at the end of the first week of therapy, serum levels of conjugated ursodeoxycholic acid (CUDCA) showed a gradual decrease. Conjugated cholic acid (CCA) and chenodeoxycholic acid (CCDCA) showed a progressive decrease with the resolution of viral hepatitis, but no influence of UDCA administration was observed. CONCLUSIONS: Our study demonstrates that UDCA significantly improves cholestatic indices in patients with acute viral hepatitis, but this effect does not seem to affect the course of the illness.     

Effect of sodium butyrate on gastric ulcer aggravation and hepatic injury inflicted by bile duct ligation in rats

Background and AimCholestasis is positively associated with an increased risk of peptic ulceration. The present study investigated the aggravating effect of cholestasis on piroxicam-induced gastric ulceration. The study also evaluated the effect of sodium butyrate (SoB) on piroxicam-induced gastric ulceration in cholestatic animals and its effect on hepatic tissues and both effects were compared to ursodeoxycholic acid (UDCA) as a standard anticholestatic drug.MethodsBile duct ligation was adopted for induction of cholestasis in rats. The cholestatic animals received saline, SoB (P.O, 400 mg/kg, twice daily) or UDCA (P.O, 30 mg/kg/day) for 4 days starting from the first day of surgery. On the 4th day, blood samples were collected for determination of serum hepatic markers, then gastric ulcers were induced by piroxicam administration (P.O, 50 mg/kg) and 4 h later, the stomach was isolated and gastric mucosa was collected for biochemical determinations. The ulcer indices for the investigated drugs were compared to omeprazole as a standard acid suppressive drug.ResultsPiroxicam-induced ulceration was exacerbated in cholestatic rats. Gastric mucosa showed a significant elevation of MDA and TNF-α together with a significant decrease in GSH &VEGF levels. SoB treatment significantly attenuated ulcer development. The afforded protection was higher than that provided by UDCA and was not significantly different from that afforded by omeprazole. SoB significantly decreased gastric mucosal MDA and TNF-α level, whereas UDCA failed to alter these parameters. Both drugs significantly elevated GSH, VEGF and IL10 levels. Similar to UDCA, SoB showed a significant reduction in AST, ALT, GGT, ALP and bilirubin level. Histopathological examination confirmed the attenuating effect of SoB on gastric and hepatic injury.ConclusionsSodium butyrate effectively protected gastric and hepatic tissues against cholestasis-induced damage. Gastroprotection was mediated through antioxidant, anti-inflammatory and angiogenic activities.     

Ursodeoxycholic acid stimulates the formation of the bile canalicular network

Ursodeoxycholic acid (UDCA) is a hepatoprotective bile acid used in the treatment of chronic liver diseases. Although several pharmacological effects, including choleresis and inhibition of apoptosis, have been proposed, the impact of UDCA on hepatic structure is not well understood. Here, the influence of UDCA on bile canalicular (BC) morphology was evaluated in vitro in immortalized rat hepatocytes (McA-RH 7777 cells) and primary rat hepatocytes. Cells cultured for 3 days in the presence of UDCA, the BC lumen was enlarged and the bile canaliculi were surrounded by multiple cells (≥5) with a continuous canal-like structure, reminiscent of the in vivo BC network. The effects were dependent on p38MAPK and conventional PKC in McA-RH cells, and partially dependent on p38MAPK, MAPK/ERK kinase, and conventional PKC in primary rat hepatocytes. These findings were then studied in vivo in a rat model of dimethylnitrosamine-induced hepatic injury, in which the BC network is significantly disrupted. In accordance with the in vitro observations, administration of UDCA (40mg/kg/day) to the injured rats for 18 days improved the BC network compared with the vehicle control. Serum hepatic markers were not altered by UDCA treatment, suggesting that the morphological effects were due to the direct actions of UDCA on network formation. Our data provide new evidence of the pharmacological potential of UDCA in accelerating or regenerating BC network formation in vitro, in hepatic cell culture models, and in vivo in a rat model of hepatic injury, and provide a basis for understanding its hepatoprotective effects.     

Ursodeoxycholic acid inhibits pro-inflammatory repertoires,IL-1β and nitric oxide in rat microglia

Ursodeoxycholic acid (UDCA) is a non-toxic, hydrophilic bile acid in widespread clinical use mainly for acute and chronic liver disease. Recently, treatment with UDCA in hepatic graft-versus-host disease has been given in immunosuppressive therapy for improvement of the biochemical markers of cholestasis. Moreover, it has been reported that UDCA possesses immunomodulatory effects by the suppression of cytokine production. In the present study, we hypothesized that UDCA may inhibit the production of the pro-inflammatory cytokine, IL-1beta, and nitric oxide (NO) in microglia. In the study, we found that 100 microg/mL UDCA effectively inhibited these two pro-inflammatory factors at 24 h and 48 h, compared to the Abeta42-pretreated groups. These results were compared with the LPS+UDCA group to confirm the UDCA effect. As microglia can be activated by several stimulants, such as Abeta42, in Alzheimers brain and can release those inflammatory factors, the ability to inhibit or at least decrease the production of IL-1beta and NO in Alzheimers disease (AD) is essential. Using RT-PCR, ELISA and the Griess Reagent System, we therefore found that UDCA in Abeta42 pre-treated cultures played a significant role in suppressing the expression or the production of IL-1beta and NO. Similarly, lipopolysaccharide (LPS) did not activate microglia in the presence of UDCA. Moreover, we found that UDCA exhibits a prolonged effect on microglial cells (up to 48 h), which suggests that UDCA may play an important role in chronic cell damage due to this long effect. These results further imply that UDCA could be an important cue in suppressing the microglial activation stimulated by massive Aa peptides in the AD progressing brain.