利胆通络解毒方联合熊去氧胆酸治疗原发性胆汁性肝硬化

目的观察利胆通络解毒方联合熊去氧胆酸治疗原发性胆汁性肝硬化的临床疗效。方法 48例原发性胆汁性肝硬化（PBC）患者,随机分为观察组和对照组,每组24例。观察组患者给予利胆通络解毒方联合熊去氧胆酸治疗,对照组仅给予熊去氧胆酸治疗,两组患者均治疗6个月,观察临床治疗效果。结果观察组的总有效率91.67%高于对照组58.33%,两组比较差异有统计学意义（P〈0.05）。结论利胆通络解毒方联合熊去氧胆酸治疗原发性胆汁性肝硬化临床疗效肯定,值得推广应用。     

熊去氧胆酸联合复方甘草酸苷治疗原发性胆汁性肝硬化疗效观察

目的观察熊去氧胆酸联合复方甘草酸苷治疗原发性胆汁性肝硬化（PBC）的临床疗效。方法将32例原发性胆汁性肝硬化患者随机分为治疗组和对照组,治疗组给予熊去氧胆酸联合复方甘草酸苷治疗,对照组单用熊去氧胆酸治疗,疗程4～6周,观察两组的疗效及不良反应情况。结果两组患者治疗后肝功能相关生化指标及临床疗效较治疗前均有改善,且治疗组优于对照组（P〈0.05）,两组均无严重不良反应发生。结论熊去氧胆酸联合复方甘草酸苷治疗原发性胆汁性肝硬化疗效显著,安全有效。     

关于原发性胆汁性肝硬化诊断和治疗的体会

目的总结分析原发性胆汁性肝硬化（PBC）患者的临床特征和诊疗经验,为进一步提高该病诊疗水平提供一定临床依据。方法采用回顾性分析的方法,收集2006年5月至2012年5月间某医院某科室收治的PBC住院病例一般情况、临床症状和体征、实验室检查结果及预后等资料,按其治疗方案的不同分为常规保肝药物治疗组（甲组）,保肝药物加熊去胆酸治疗组（乙组）,保肝药物加皮质类固醇治疗组（丙组）,以及保肝药物、熊去胆酸加皮质类固醇联合治疗组（丁组）。通过比较四组患者的治疗的有效率和临床症状及体征的改善情况,回顾性地探讨PBC的最佳诊疗方案。结果 61例病例有39例经治疗后病情好转,治疗的总有效率为63.93%,无效22例。甲组的有效率和临床症状减轻率均较低,差异有统计学意义（P〈0.05）。结论 PBC患者早期临床表现不典型,ALP增高和AMA阳性或为PBC的早期诊断指标;单纯保肝药物治疗PBC效果不佳,熊去胆酸或皮质类固醇联合用药治疗一定程度上可提高疗效。     

熊去氧胆酸联合通胆汤对原发性胆汁性肝硬化的治疗作用

目的探究熊去氧胆酸联合通胆汤对原发性胆汁性肝硬化治疗作用。方法观察组给予基础治疗、熊去氧胆酸(UDCA)和通胆汤治疗;对照组给予基础治疗、熊去氧胆酸(UDCA)。结果对观察组行熊去氧胆酸(UDCA)联合通胆汤治疗,治疗12周其完全反应率为83.3%,较对照组53.3%,有显著差异,P<0.05。结论熊去氧胆酸(UDCA)能够有效缓解早中期的PBC患者的病情,若加用通胆汤,能够加速完全反应时间,使之更好地改善临床症状,提高患者生活质量,具有积极的临床意义。     

口服熊去氧胆酸治疗原发性胆汁性肝硬化28例临床分析

原发性胆汁性肝硬化(Primary biliary cirrhosis,PBC)是一种病因未明的慢性进行性胆汁淤积性肝病,发病机制可能与自身免疫有关。熊去氧胆酸(UDCA)在PBC的治疗中扮演越来越重要的角色,笔者用UDCA治疗PBC28例,取得了满     

复方甘草酸苷片联合熊去氧胆酸治疗原发性胆汁性肝硬化疗效分析

<正>熊去氧胆酸(UDCA)是目前较为肯定的治疗原发性胆汁性肝硬化(PBC)有疗效的药物.本文复方甘草酸苷片联合UDCA治疗PBC取得较好疗效1资料与方法1.1研究对象选病历为1997年1月至2005年12月在我院门诊及住院的PBC患者共68例,所有病例均符合2000年中华医学会肝脏病学会     

熊去氧胆酸胶囊在原发性胆汁性肝硬化的疗效分析

目的分析熊去氧胆酸胶囊治疗原发性胆汁淤积性肝硬化的疗效,提高对该病诊治的认识。方法将46例入选患者,随机分为两组。应用熊去氧胆酸胶囊治疗组与对照组的患者治疗前后的临床特征、各项生化等指标并进行统计学分析。结果 46例患者治疗前,两组肝功能无明显差异。治疗组在治疗前后ALT、AST、TBil、ALP、GGT存在差异,对照组在治疗前后ALT、AST、TBil存在差异,两组治疗后肝功能比较,TBil存在差异。治疗后26例治疗组中18例患者显效,7例患者有效,总有效率96.2%;而对照组20例中,4例显著有效,6例有效,总有效率50%,两组病例治疗后有明显的统计学意义。在治疗过程中患者耐受性好,未见明显不良反应。结论熊去氧胆酸胶囊可明显改善PBC患者的临床症状和肝功能生化指标,是目前治疗PBC的首选药物。     

原发性胆汁性肝硬化的药物治疗

熊去氧胆酸是目前治疗原发性胆汁性肝硬化的唯一公认药物,可以改善早期患者的长期预后;对于熊去氧胆酸疗效不佳者迫切需要其他有效治疗药物治疗,但糖皮质激素、免疫抑制药或其他药物的疗效及安全性尚需更多的临床研究证实;终末期患者适合肝移植治疗。本文就原发性胆汁性肝硬化的药物治疗进展进行综述。     

熊去氧胆酸治疗胆汁郁积性疾病的机制与应用

<正> 熊去氧胆酸(UDCA)正越来越多地应用于慢性胆汁淤积性肝脏病的治疗。首次报道是在80年代,目前UDCA是治疗原发性胆管硬化症(PBC)有效的药物,但UDCA作用机制还未完全弄清。本文就UDCA治疗胆汁郁积性疾病的作用机制和临床应用做一综述: 1 UDCA的物理化学和药理学特性     

扶正化瘀胶囊联用熊去氧胆酸治疗原发性胆汁性肝硬化的近期疗效观察及护理

目的探讨扶正化瘀胶囊联合熊去氧胆酸治疗原发性胆汁性肝硬化(PBC)的疗效。方法 130例PBC患者随机分为观察组与对照组各65例,常规护肝及对症支持治疗基础上,对照组单用熊去氧胆酸治疗,观察组加用扶正化瘀胶囊,疗程24周。结果治疗后两组患者肝功能指标均显著改善,观察组各项指标降低幅度较对照组更为明显(P<0.01);观察组完全反应率84.6%明显高于对照组63.1%(P<0.01)。结论扶正化瘀胶囊联用熊去氧胆酸治疗PBC疗效确切,安全性好。     

腺苷蛋氨酸联合前列地尔治疗原发性胆汁性肝硬化的疗效观察

目的对比观察在使用传统熊去氧胆酸胶囊基础上联合腺苷蛋氨酸及前列地尔治疗原发性胆汁性肝硬化的疗效。方法将40例原发性胆汁性肝硬化患者随机分为2组,每纽20例。对照组给予熊去氧胆酸胶囊0．25g每天3次口服,共3个月。治疗组在上述基础上给予每天静滴腺苷蛋氨酸针1g联合前列地尔针20IU治疗,共10d,每月一次,共3次。结果随访3个月,按肝功能改善情况评分,治疗组优良率为82．68％,对照组优良率为65．12％,经统计分析,P〈0．05。结论腺苷蛋氨酸联合前列地尔对原发性胆汁性肝硬化的治疗可比传统单用熊去氧胆酸胶囊治疗取得更为良好的疗效。     

Celiac disease, primary biliary cirrhosis and helicobacter pylori infection: one link for three diseases

The association between celiac disease (CD) and primary biliary cirrhosis (PBC) has been reported in literature. Recent epidemiological studies showed an increased prevalence of CD in patients with PBC and vice versa. The cause of PBC is unknown. However, considerable evidence points to an autoimmune basis. The role of infectious agents, such as Helicobacter pylori (H. pylori), has been proposed to stimulate antibody cross-reaction with mitochondria of the bile duct cells. We report a case of a 36-year-old woman with diagnosis of CD, PBC and H. pylori infection. Strict adherence to gluten-free diet, associated to ursodeoxycholic acid (UDCA) administration and eradication treatment for H. pylori infection, led to a marked improvement of clinical status. Our experience supports the pathogenetic role of increased intestinal permeability in the course of CD and H. pylori infection to induce PBC. Future studies are needed to clarify this link to, and in particular the role played by abnormal intestinal permeability and infectious agents in the pathogenesis of PBC.     

Obeticholic acid for the treatment of primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is characterized by progressive nonsuppurative destruction of small bile ducts, resulting in intrahepatic cholestasis, fibrosis and ultimately end-stage liver disease. Timely intervention with ursodeoxycholic acid is associated with excellent survival, although approximately one-third of all patients fail to achieve biochemical response, signifying a critical need for additional therapeutic strategies. Obeticholic acid (OCA) is a potent ligand of the nuclear hormone receptor farnesoid X receptor (FXR). Activation of FXR inhibits bile acid synthesis and protects against toxic accumulation in models of cholestasis and facilitates hepatic regeneration in preclinical studies. Data from recent Phase II and III controlled trials suggest a therapeutic impact of OCA in PBC biochemical nonresponders, as evidenced by change in proven laboratory surrogates of long-term outcome. Dose-dependent pruritus is a common adverse effect, but may be overcome through dose-titration. Longer term studies are needed with focus on safety and long-term clinical efficacy.     

Investigational drugs in phase II clinical trials for primary biliary cholangitis

Introduction: Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease that may lead to biliary fibrosis, and eventually cirrhosis. The primary treatment for PBC is ursodeoxycholic acid (UDCA), which has favorably altered its natural history. However, up to 40% of patients have an inadequate response to UDCA, and are therefore at high risk of liver-related complications. Obeticholic acid has recently been approved for use in patients with PBC with inadequate response or who are intolerant to UDCA, but improvement in long-term outcomes has not yet been demonstrated. Alternative therapeutic options for PBC are needed.

Areas covered: Recent advances in research including epidemiological, genetic and pre-clinical studies in animal models of PBC have yielded numerous agents currently at different stages of development for treatment of patients with PBC; in this review, we cover novel therapies that were recently or are recently being investigated in phase II clinical trials.

Expert opinion: Despite the evolving landscape in PBC, the main challenges facing development of novel therapies remain the rarity of the disease and the limitations to design and conduct of controlled clinical trials in PBC, which are needed to determine the long-term effects of novel therapies on the clinical outcomes of PBC.     

38例原发性胆汁性肝硬化的临床特征

目的分析原发性胆汁性肝硬化患者的临床特征,提高临床诊治水平。方法对38例原发性胆汁性肝硬化患者的一般资料、临床表现、生化指标、免疫学等变化及治疗应答反应等进行回顾性分析。结果本组患者平均年龄为（50±14）岁,其中女性占81．57％（31／38）。临床症状以乏力最为常见,其次为脾大、黄疸、皮肤瘙痒等,患者血清碱性磷酸酶及γ-谷氨酰转肽酶水平明显升高,而血清ALT、AST、球蛋白水平仅轻中度升高,100％（38／38）患者抗线粒体抗体和（或）抗线粒体抗体M2阳性。应用熊去氧胆酸有助于改善生化指标,而激素治疗效果不佳且易引起继发感染。结论PBC多发生于中年女性,最常见的症状是乏力,血清AKP、γ-GT水平升高及抗线粒体抗体／抗线粒体抗体M2亚型阳性有助于诊断本病。熊去氧胆酸治疗有效,慎用激素。     

Primary biliary cirrhosis: safety and benefits of established and emerging therapies

Introduction: Primary biliary cirrhosis (PBC) is a chronic, cholestatic liver disease characterized histologically by lymphocytic cholangitis and intralobular bile duct destruction. It is a progressive disorder associated with increased mortality and decreased quality of life related to hepatic fibrosis, troublesome symptoms such as fatigue and pruritus, and ultimately endstage cirrhosis. PBC affects adults around the world, and therefore effective treatment of PBC and its associated symptoms constitute significant issues for patients and providers as well as on a public health level. The only approved pharmacotherapy for PBC to date is ursodeoxycholic acid (UDCA), a choleretic, hydrophilic bile acid which has been in clinical use for decades. UDCA is effective in a majority of patients with PBC, but nearly a third of patients are UDCA non-responders. Non-response to UDCA is associated with an increased risk of death or need for liver transplantation (LT). Whereas LT is an effective treatment, it engenders substantial cost and a risk of PBC recurrence, among other complications. Patients who are non-responders to UDCA or have highly symptomatic disease (e.g., intractable pruritus) are thus in critical need of novel therapeutic approaches, which are both safe and effective.

Areas covered: In this review, we provide a synopsis regarding the safety and benefits of established and emerging pharmacotherapies for PBC and present viewpoints on how they may evolve over the next several years.

Expert opinion: It is our belief that the pharmacoscope of PBC, as with other cholestatic liver diseases, is likely to see important advancements in the near future.     

Advances in pharmacotherapy for primary biliary cirrhosis

Introduction: Primary biliary cirrhosis (PBC) is a chronic autoimmune liver disease mostly seen in middle-aged women characterized by progressive nonsuppurative destruction of small bile ducts resulting in intrahepatic cholestasis, parenchymal injury and ultimately end-stage liver disease. Despite major breakthroughs in our understanding of PBC, there remains only one FDA-approved agent for treatment: ursodeoxycholic acid (UDCA) to which one-third of patients are unresponsive.

Areas covered: Biochemical response to treatment with UDCA is associated with excellent survival rates in PBC patients. However, there is a need for alternative treatments for nonresponders. Results from human epidemiological and genetic studies as well as preclinical studies in PBC animal models have provided a strong impetus for the development of new therapeutic agents. In this review, we discuss the recent advances in translational research in PBC focusing on promising therapeutic approaches, namely immune-based targeted therapies and agents targeting the synthesis and circulation of bile acids.

Expert opinion: We are in a new era for the development of novel therapies for PBC. Data on fibrates, budesonide and obeticholic acid offer encouragement for nonresponders to UDCA.     

Obeticholic acid and budesonide for the treatment of primary biliary cirrhosis

Introduction: Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease of adults. Treatments are needed when patients have incomplete response to ursodeoxycholic acid (UDCA).

Areas covered: Discoveries of the key role played by bile acids (BAs) and nuclear receptors (NRs) in regulating liver and metabolic homeostasis have led to promising therapeutic approaches in liver diseases. A PubMed search for the recent literature on NRs in liver disease was conducted. In particular, obeticholic acid (OCA) is a farnesoid X receptor (FXR) agonist that has an important role in the enterohepatic circulation of BAs. Preliminary studies of OCA in patients with PBC have demonstrated marked biochemical improvement when administered in combination with UDCA and alone. Pruritus is the most common side effect, limiting treatment at higher doses. Budesonide is a glucocorticoid receptor/pregnane X receptor (PXR) agonist also involved in BA synthesis, metabolism and transport. Studies with budesonide have shown positive effects of short-term combination therapy in selected patients with early stage disease and overlapping features of autoimmune hepatitis.

Expert opinion: Though larger studies are needed, preliminary results of agents targeting FXR and PXR have been encouraging, particularly in subsets of patients with PBC and may mark a new therapeutic era.     

Multicentre randomized placebo-controlled trial of ursodeoxycholic acid with or without colchicine in symptomatic primary biliary cirrhosis

AIM: To establish the efficacy of combination therapy with ursodeoxycholic acid (UDCA) and colchicine in patients with symptomatic primary biliary cirrhosis (PBC), defined by the presence of liver cirrhosis, pruritus or bilirubin exceeding 2 mg/mL. METHODS: A total of 90 patients were randomly assigned to ursodeoxycholic acid 500 mg/daily plus placebo (UDCA group, n=44), or ursodeoxycholic acid at the same dosage plus colchicine, 1 mg/daily (UDCA/C group, n=46). The two groups were comparable for age, sex, stage of disease, severity of pruritus, bilirubin, and Mayo score. All patients underwent clinical, ultrasonographic, and biochemical examinations at entry and then every 6 months up to 3 years of follow-up. Patients with cirrhosis underwent endoscopy every 12 months. In a sub-group of patients without cirrhosis, who consented, liver biopsy was repeated at the end of the study. RESULTS: The number of treatment failures (i.e. dead, orthotopic liver transplantation (OLT), complications of cirrhosis, doubling of bilirubin, untreatable pruritus) was 11 (25%) in the UDCA group and four (9%) in the UDCA/C group (P < 0.05). No significant differences were observed in terms of improvement of liver enzymes related to cholestasis and cytolysis and of amelioration of pruritus. The Mayo score values increased less above the baseline values at 24 and 36 month-intervals in the UDCA/C group than in the UDCA group. Histological evaluation at baseline and at the end of the study was available for 15 patients with pre-cirrhotic stage. A significant reduction in histological grading score was observed in patients from the UDCA/C group, whereas no changes in these histological scores were observed in the UDCA group. CONCLUSIONS: The addition of colchicine to ursodeoxycholic acid in patients with symptomatic primary biliary cirrhosis results in a small but significant reduction of disease progress.