应用奥贝胆酸和贝特类药物治疗对熊去氧胆酸治疗不完全应答的原发性胆汁性胆管炎患者临床研究

目的 探讨应用奥贝胆酸(OCA)和贝特类药物治疗对熊去氧胆酸(UDCA)治疗不完全应答的原发性胆汁性胆管炎(PBC)患者的临床疗效。方法 2019年1月～2020年12月我院收治的PBC患者41例,被随机分为观察组21例和对照组20例。所有患者在继续UDCA维持治疗的基础上,给予对照组OCA治疗,给予观察组OCA联合非诺贝特治疗,两组均治疗观察24 w。采用放射免疫法检测血清IV型胶原(IV-C)、透明质酸(HA)、III型前胶原(PⅢP)和层粘连蛋白(LN)水平,采用免疫比浊法检测血清免疫球蛋白G(IgG)、IgA和IgM,采用ELISA法检测血清白细胞介素-2(IL-2)、IL-6、IL-10和肿瘤坏死因子-α(TNF-α)。结果 在治疗24 w末,观察组血清ALT、TBIL、GGT和ALP水平分别为(29.1±5.3)U/L、(24.8±4.1)μmol/L、(86.4±15.7)U/L和(100.6±26.3)U/L,均显著低于对照组【分别为(42.8±7.6)U/L、(30.2±6.5)μmol/L、(121.7±18.6)U/L和(131.8±33.7)U/L,P<0...     

熊去氧胆酸联合甘草酸二铵治疗原发性 胆汁性胆管炎的效果观察

目的对比熊去氧胆酸(UDCA)联合甘草酸二铵与单用UDCA治疗原发性胆汁性胆管炎(PBC)的生化学应答和肝脏硬度变化情况。方法选取2014年1月-2016年3月就诊于河北医科大学第三医院中西医结合肝病科的PBC患者66例,均行FibroTouch检测,以肝脏硬度值表示肝纤维化程度,对比分析UDCA联合甘草酸二铵与单用UDCA治疗PBC患者4、12、24和48周的肝生化学应答和治疗24、48周后肝脏硬度值变化情况。两组间计量资料比较采用两独立样本t检验,治疗前后生化学指标及肝脏硬度值比较采用配对t检验。结果 UDCA联合甘草酸二铵治疗组与单用UDCA对照组比较,联合治疗组AST水平在治疗后4周[(38. 4±15. 4) U/L vs (61. 6±28. 8) U/L,t=2. 684,P=0. 012]、12周[(36. 4±12. 6) U/L vs (58. 1±24. 8) U/L,t=2. 953,P=0. 006)]、24周[(37. 0±8. 5) U/L vs (52. 9±17. 2) U/L,t=3. 134,P=0. 004]、48周[(34. 9±7. 9) U/L vs (48. 6±12. 7) U/L,t=3. 242,P=0. 003]均显著低于对照组;联合治疗组ALP水平在治疗24周[(91. 6±15. 1) U/L vs (137. 3±55. 6) U/L,t=2. 970,P=0. 006]、48周[(71. 3±14. 7) U/L vs (128. 7±45. 5) U/L,t=4. 503,P 0. 001]均显著低于对照组。对照组、联合治疗组肝脏硬度值治疗后24周[(12. 9±6. 8) kPa vs (13. 9±7. 6) kPa,t=4. 814,P 0. 001;(13. 4±7. 0) k Pa vs (15. 8±9. 7) k Pa,t=3. 031,P=0. 010)]、48周[(12. 6±6. 4) kPa vs (13. 9±7. 6) kPa,t=3. 928,P=0. 010;(12. 0±5. 7) k Pa vs (15. 8±9. 7) k Pa,t=3. 044,P=0. 010)]均较治疗前显著降低;但两组之间肝脏硬度值在治疗24周、48周无显著差异(P值均 0. 05)。结论 UDCA联合甘草酸二铵治疗PBC可改善患者的血清生化学应答反应,优于单用UDCA治疗,两组治疗24周、48周肝脏硬度值较治疗前有显著下降,有利于病情稳定。FibroTouch在PBC患者定期随访监测时对判断肝纤维化有无进展有一定的应用价值。     

对熊去氧胆酸应答不佳或不耐受的原发性胆汁性胆管炎患者应用奥贝胆酸和贝特类药物治疗的研究进展

熊去氧胆酸治疗原发性胆汁性胆管炎会发生应答不佳或不耐受,更换为奥贝胆酸或贝特类单药或联合治疗后,部分治疗方案也会出现应答不佳或不耐受。近年奥贝胆酸和贝特类药物临床研究逐步解决这些问题,奥贝胆酸/贝特类药物与熊去氧胆酸的联合治疗对非晚期肝硬化原发性胆汁性胆管炎患者是有效和安全的。     

中药联合熊去氧胆酸治疗原发性胆汁性胆管炎临床疗效Meta分析

目的:通过Meta分析评价中药联合熊去氧胆酸治疗原发性胆汁性胆管炎(PBC)的临床疗效。方法:应用计算机从Cochrane Library、Pub Med、中国期刊全文数据库(CNKI)、中文科技期刊全文数据库(VIP)、中国生物医学文献数据库(CBM)、万方医药期刊全文及学位论文数据库中,搜索中药联合熊去氧胆酸(UDCA)和单用UDCA治疗PBC的随机对照试验(RCT)文献,截止日期到2017年12月,对纳入文献进行资料提取和文献偏倚风险评估并采用RevMan5.3进行分析。结果:结果:共纳入6项RCT试验,共401例患者,其中治疗组201例,对照组200例。Meta分析显示中药联合UDCA治疗PBC患者24周后,在提高临床症状改善率[OR=5.99,95%CI(3.71,9.68),P<0.05]、降低肝功能指标ALP[MD=-27.10,95%CI(-31.99,-22.21),P<0.05]、GGT[MD=-17.69,95%CI(-23.67,-11.71),P<0.05]、ALT[MD=-16.85,95%CI(-21.18,-12.52),P<0.05]、AST[MD=-8.67,95%CI(-11.19,-6.16),P<0.05]、降低总胆红素TBil[MD=-10.43,95%CI(-14.34,-6.52),P<0.05]、降低总胆汁酸TBil[MD=-12.24,95%CI(-20.83,-3.65),P<0.05],均优于对照组,复发率两组无差异统计学意义[OR=0.56,95%CI(0.14,2.23),P=0.41]。结论:中药联合UDCA治疗PBC在24周内对改善临床症状以及肝功能指标优于单独使用熊去氧胆酸治疗,但受纳入的RCT研究样本量和质量的限制且存在不明确和高风险偏倚,上述结论需更高质量的研究再验证。     

原发性胆汁性胆管炎合并胆结石的临床特征及熊去氧胆酸治疗应答情况

目的 探讨原发性胆汁性胆管炎(primary biliary cholangitis, PBC)合并胆结石和PBC未合并胆结石患者的临床特征,并比较两组患者使用熊去氧胆酸(ursodeoxycholic acid, UDCA)治疗后应答情况。方法 回顾性分析2015年6月至2020年6月于空军军医大学第一附属医院就诊的1 102例自身免疫性肝病(autoimmune liver disease, AILD)患者的临床资料,筛选出PBC患者872例。分析PBC合并胆结石组和PBC未合并胆结石组的基本特征、实验室检查指标情况,并比较两组患者服用UDCA治疗后肝功变化及生化应答情况。结果 PBC患者合并胆结石比例为21.9%(191/872)。PBC合并胆结石组的首诊年龄、确诊时肝硬化比例较PBC未合并胆结石组高(P<0.001),且PBC合并胆结石组确诊时ALB、AST、ALT、GGT水平均较PBC未合并胆结石组低(P<0.05)。服用UDCA治疗1年后,两组肝功指标均较治疗前明显改善(P<0.05),PBC合并胆结石组AST、ALT、ALP、GGT下降程度低于PBC未合...     

原发性胆汁性肝硬化的熊去氧胆酸治疗

原发性胆汁性肝硬化 (ｐｒｉｍａｒｙｂｉｌｉａｒｙｃｉｒｒｈｏｓｉｓ ,ＰＢＣ)是一种好发于中年女性的自身免疫性病变 ,其病理特征是慢性进行性肝内小叶间胆管和中隔胆管的非化脓性炎性破坏及淋巴肉芽肿。其自然进程约 2 0年 ,自出现症状至死于肝功能衰竭或食管静脉曲张破裂约 10年。治疗原则包括对症处理、免疫调节、消炎利胆和抗纤维化及肝移植。其中熊去氧胆酸 (ＵＤＣＡ)是当今公认的治疗ＰＢＣ的主要药物。一、ＵＤＣＡ对ＰＢＣ的组织学改善(一 )门静脉周围组织学改善　在ＰＢＣ肝内小胆管 (外径小于 10 0 μｍ的小叶间胆管 )是主要…     

熊去氧胆酸治疗原发性胆汁性肝硬化的疗效分析

目的评价熊去氧胆酸治疗原发性胆汁性肝硬化的疗效。方法18例原发性胆汁性肝硬化患者口服UDCA 10~15mg.kg-1.d-1,服药时间均2年以上。于服药后1、3、6、12、18、24个月时分别复查肝功能。服药前及服药后12个月和24个月时行快速肝穿刺法取肝组织常规行病理检查。结果18例患者主要表现为GGT及ALP的升高,AST、ALT均轻至中度升高。UDCA治疗PBC所有患者的生化指标均有明显改善,其中以ALT和AST下降迅速,在3个月后明显下降,6个月时基本恢复正常,而GGT和ALP则下降缓慢,ALP于12个月后恢复正常,24个月后仍有大部分病人GGT仍未恢复正常。12例肝活检患者12个月后共有5例肝组织学病理变化得到改善。结论UDCA能显著改善PBC患者的肝功能变化,长期应用UDCA治疗可延缓肝脏组织学进展。     

熊去氧胆酸治疗原发性胆汁性肝硬化疗效观察

原发性胆汁性肝硬化(PBC)是一种原因不明的自身免疫性疾病，迄今尚无特效药物治疗。1996年4月至2003年10月，我们采用熊去氧胆酸(UDCA)治疗PBC患者41例，取得较满意疗效。现报告如下。     

熊去氧胆酸治疗老年原发性胆汁性肝硬化的临床研究

目的探讨老年原发性胆汁肝硬化（PBC）的临床特征、诊断和治疗效果。方法将66例诊断为PBC的病人分为老年组40例,中年组26例,比较两组的临床表现、生化免疫指标（碱性磷酸酶：ALP、谷氨酰转肽酶：GGT、抗线粒体抗体：AMA）。两组病例均给予口服熊去氧胆酸（UDCA：优思弗）治疗,服药8W后比较疗效。结果90％病人因体检发现ALP、GGT升高就诊,治疗前两组患者的ALP、GGT升高程度差异无统计学意义（P〉0．05）。非特异性皮肤瘙痒是老年PBC患者的主要表现,中年组患者中88．5％无症状,明显高于老年组的37．5％;口服优思弗8W后,两组ALP、GGT均较治疗前明显程度降低（P〈0．05）。老年组中3例肝硬化患者服用优思弗后,其症状、体征及ALP、GGT均无改善,2例死亡。服药后两组患者乏力、皮肤瘙痒症状均无改善,影像学也无变化。结论：（1）PBC早期缺乏特异症状;（2）AMA对PBC诊断有重要意义,ALP、GGT的升高早于黄疸、肝肿大出现。（3）应重视体检中无法解释的ALP、GGT异常升高。（4）UDCA对早期原发性胆汁肝硬化疗效满意。（5）老龄可能是影响PBC患者预后的因素之一。     

熊去氧胆酸治疗原发性胆汁性肝硬化1年总结报告

目的评价长期使用熊去氧胆酸（UDCA）治疗原发性胆汁性肝硬化（PBC）的疗效及安全性。方法应用13～15mg·kg^-1·d^-1UDCA治疗18例PBC患者,治疗1年时观察患者的临床症状、体征及实验室检查的变化。结果18例患者经过UDCA治疗1年后,临床症状及体征多无明显改善,血γ-谷氨酰转肽酶、碱性磷酸酶、丙氨酸氨基转移酶、天冬氨酸氨基转移酶、总胆汁酸和总胆红素均有显著下降（P〈0.01）,血总胆固醇、球蛋白和IgM、IgG亦有所下降（P〈0.05）,但血白蛋白和凝血酶原时间无变化。患者在治疗中除少数病例有轻微腹泻外无其他药物不良反应发生。结论UDCA能有效改善患者的血生化学指标,但不能有效地改善多数患者的症状和体征。患者及早并长期应用UDCA可能能延缓疾病的进展。     

Asymptomatic primary sclerosing cholangitis treated with ursodeoxycholic acid

Ursodeoxycholic acid treatment (600 mg/day) was evaluated in a patient with asymptomatic primary sclerosing cholangitis. Serum levels of biliary enzymes decreased to normal ranges within 1 month's treatment and remained normal for 26 months. Serum chenodeoxycholic acid had been replaced by ursodeoxycholic acid, and hepatic copper metabolism, assessed by x-ray probe analysis, improved during the treatment. However, neither biliary tract sclerosis nor portal tract pathology changed with the treatment. These observations suggest that ursodeoxycholic acid protects the liver in primary sclerosing cholangitis by improving the metabolism of bile acid and copper.     

The association of histological progression with biochemical response to ursodeoxycholic acid in primary biliary cholangitis

Primary biliary cholangitis (PBC) is currently diagnosed at an early stage; therefore, the number of patients with PBC without symptoms at the time of diagnosis is increasing. However, up to 30% of patients with PBC exhibit the suboptimal response to ursodeoxycholic acid (UDCA) and are at high risk of end-stage liver disease. Obeticholic acid is an approved second-line therapy for patients with PBC that are refractory to UDCA. Novel surrogate endpoints are required to identify individuals eligible for second-line therapies. An inadequate biochemical response to UDCA is a useful predictor of poor outcomes in patients with PBC. In addition to UDCA effects on biochemical parameters, histological outcomes could be considered as candidate surrogate endpoints. Alterations in liver histology are used as surrogate endpoints in clinical studies. However, current staging systems are insufficient to determine PBC disease severity and progression because of the pathological heterogeneity of the disease. Histological features at baseline and biochemical response to UDCA treatment can affect the disease course of PBC. Therefore, novel surrogate endpoints must be represented by parameters characterized by histological outcomes and treatment responses in PBC. In this review, we discuss the existing histological parameters and newly created factors to identify patients with PBC who are at a high risk of developing end-stage liver disease and, consequently, the potential need for additional treatments.     

Additive improvement induced by bezafibrate in patients with primary biliary cirrhosis showing refractory response to ursodeoxycholic acid

Background and Aim: Ursodeoxycholic acid (UDCA) has been widely used in the treatment of patients with primary biliary cirrhosis (PBC). However, some patients are refractory to UDCA. The aim of this study is to clarify the additive improvement induced by bezafibrate in patients refractory to UDCA. Methods: This study was a prospective analysis of 37 consecutive PBC patients. All patients were treated first for 6 months with UDCA, and then with bezafibrate, if their alkaline phosphatase (ALP) levels did not decrease more than 40% or within the normal range after 6 months' treatment with UDCA. Clinical parameters were monitored for the subsequent 24 months. Result: Twenty‐two patients (59%) achieved improvement of ALP levels after the treatment with UDCA. Those patients (Group A) had significantly lower levels of ALP at diagnosis than those with abnormal ALP levels after 6 months' treatment with UDCA (Group B; P = 0.020). They continued UDCA monotherapy, and maintained normal ALP levels at subsequent follow ups. However, immunoglobulin M (IgM) levels remained abnormal in eight patients, whose IgM levels at the time of diagnosis were significantly higher than those whose IgM were normalized after 6 months' treatment with UDCA (P = 0.026). Those in Group B were treated additionally with bezafibrate, and 12 patients (80%) achieved normal ALP and IgM levels within 12 months of commencement of therapy. Conclusion: Higher ALP level at diagnosis is one of the predictors for UDCA failure. Combination treatment of bezafibrate in addition to UDCA may be an effective treatment for PBC patients refractory to UDCA.     

Treatment of primary biliary cirrhosis and primary sclerosing cholangitis: Use of ursodeoxycholic acid

Considerable progress has been made in the management of cholestatic liver diseases during the past decade. Various therapeutic agents have been proposed and evaluated for treatment of patients with primary biliary cirrhosis and primary sclerosing cholangitis. These treatments include ursodeoxycholic acid plus immunosuppressive and antiinflammatory drugs such as glucocorticoids, azathioprine, colchicine and methotrexate. Although these two diseases are grouped together as chronic cholestatic liver diseases, there are important differences between them, particularly with respect to response to treatment. Primary biliary cirrhosis responds much better to medical treatment. Ursodeoxycholic acid has emerged as the most commonly used medication in the treatment of these diseases. Ursodeoxycholic acid therapy is safe and has been associated with improvement of biochemical test results for liver function in patients with primary biliary cirrhosis and primary sclerosing cholangitis. However, questions remain about the long-term efficacy of the drug in halting histologic progression, although ursodeoxycholic acid does improve survival without the need for liver transplantation after 4 years of treatment in patients with primary biliary cirrhosis. Ursodeoxycholic acid is unproven in the treatment of primary sclerosing cholangitis.