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对原发性胆汁性肝硬化的疗效分析

目的:对熊去氧胆酸联合复方甘草酸苷治疗原发性胆汁性肝硬化的疗效进行评价。方法:将2010年1月—2012年12月52例原发性胆汁性肝硬化患者随机分组:试验组给予熊去氧胆酸联合复方甘草酸苷治疗,总疗程为4周;对照组仅给予复方甘草酸苷治疗,疗程相同。观察两组临床症状缓解状况及生化指标改变情况。结果:两组患者治疗前后临床症状及生化指标均有不同程度改变,但试验组明显优于对照组(P<0.05)。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确切。     

熊去氧胆酸治疗原发性胆汁性肝硬化疗效观察

目的观察熊去氧胆酸治疗原发性胆汁肝硬化的临床疗效。方法回顾性总结我院10例原发性胆汁肝硬化患者，用熊去氧胆酸10～15mg／kg．tid．po，长期服用一月、三月、半年。结果患者症状、生化指标先后均有改善。AMA无变化。结论熊去氧胆酸可显著改善生化异常，是有效治疗原发性胆汁肝硬化的首选药物。     

熊去氧胆酸联合异甘草酸镁治疗原发性胆汁性肝硬化的近期疗效观察及护理

目的观察熊去氧胆酸联合异甘草酸镁治疗原发性胆汁性肝硬化的近期疗效．探讨原发性胆汁性肝硬化护理方案。方法将18例原发性胆汁性肝硬化患者随机分为两组。治疗组11例,予熊去氧胆酸联合异甘草酸镁治疗;对照组7侧．单纯予熊去氧胆酸治疗。疗程均为4周．治疗结束后观察：丙氨酸氨基转氨酶（ALT）,总胆红素（TBIL）．碱性磷酸酶（ALP）,谷氨酰转肽酶（GGT）。结果治疗组患者治疗后肝功能各项指标均明显改善。并且治疗后TBIL和ALT与对照组比较也有显著性差异,而对照组仅GGT有显著下降。结论熊去氧胆酸联合异甘草酸镁的治疗方案加上良好的护理对原发性胆汁性肝硬化有较理想的近期教泉     

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。     

熊去氧胆酸治疗原发性胆汁性肝硬化

本文报道熊去氧胆酸治疗原发性胆汁性肝硬化。受试对象为有临床症状及典型生化改变,经活检证实的原发性胆汁性肝硬化9例。单纯以熊去氧胆酸750mg/d,至少治疗4个月。4个     

熊去氧胆酸治疗原发性胆汁性肝硬化临床观察

原发性胆汁性肝硬化是一种慢性进展性肝内胆汁淤积性疾病,发病机制尚不完全清楚,可能和自身免疫有关[1]。原发性胆汁性肝硬化治疗的关键是抑制异常的免疫反应,减轻淤积胆汁的毒性作用[2]。迄今尚无特效药物治疗。2003年5月～2009年12月间,我院采用熊去氧胆酸治疗原发性胆汁性肝硬化患者共54例,疗效满意,现报道如下。     

熊去氧胆酸治疗原发性胆汁性肝硬化82例肝功酶谱变化观察

目的观察熊去氧胆酸胶囊治疗原发性胆汁性肝硬化患者的早期疗效。方法 82例患者均给予甘草酸二铵保肝基础治疗的同时口服熊去氧胆酸胶囊每日13～15mg/kg。结果 8周后肝功酶谱ALT、AST、GGT、ALP、TBA较治疗前明显下降,前后均数比较P<0.05,具有统计学意义。结论熊去氧胆酸胶囊治疗原发性胆汁性肝硬化患者能够早期、快速改善肝脏生化学指标。     

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。     

原发性胆汁性肝硬化临床诊断及治疗研究

目的探讨原发性胆汁性肝硬化的临床诊断及治疗。方法选取笔者所在医院2007年4月～2010年9月收治的78例原发性胆汁性肝硬化患者,将78例患者随机分为两组,观察组40例,对照组38例,观察组给予异甘草酸镁静脉滴注,熊去氧胆酸胶囊治疗,对照组仅给予熊去氧胆酸治疗,同时记录所得数据。结果观察组40例患者中,显效19例,有效15例,无效6例,治疗有效率为85.0%,对照组38例患者中,显效15例,有效14例,无效9例,治疗有效率为76.3%。结论采用异甘草酸镁联合熊去氧胆酸胶囊治疗原发性胆汁性肝硬化疾病的效果显著,值得在临床推广应用。     

Obeticholic acid for the treatment of primary biliary cholangitis

Introduction: Primary biliary cholangitis (PBC) is an autoimmune disease of the liver characterized by destruction and inflammation of the intrahepatic bile ducts. The disease affects mainly women. The disease is often discovered through abnormal alkaline phosphatase (ALP) activity, and is confirmed when anti-mitochondrial antibodies (AMA) are present. The etiology of PBC is poorly understood. Cigarette smoking, immune dysregulation, nail polish, urinary tract infections, and low socioeconomic status have been implicated but none have been confirmed. Genome wide association studies (GWAS) have disclosed strong associations between certain human leukocyte antigen (HLA) alleles and PBC. PBC can progress to cirrhosis and end-stage liver disease. Hepatocellular carcinoma (HCC) develops in up to 3.5% of PBC patients. Ursodeoxycholic acid (UDCA) is the only medication approved for the treatment of PBC. The use of UDCA in PBC delays histological progression and extends the transplant-free survival. 40% of PBC patients do not respond adequately to UDCA, and these patients are at high risk for serious complications. Therefore, there is a critical need for more effective therapies for this problematic disease.

Multiple other agents have either been or are currently being studied as therapeutic options in UDCA non-responder PBC patients. Six-ethyl chenodeoxycholic acid (6-ECDCA), a potent farnesoid X receptor (FXR) agonist, has shown anti-cholestatic activity in rodent models of cholestasis. Obeticholic acid (OCA, 6-ECDCA, or INT-747), a first-in-class FXR agonist, has been examined in PBC patients with inadequate response to UDCA, and shown promising results. Particularly, initial clinical trials have demonstrated that the use of OCA (in addition to UDCA) in PBC patients with inadequate response to UDCA led to significant reduction of serum alkaline phosphatase (ALP, an important prognostic marker in PBC). More recently, the results of a randomized clinical trial of OCA monotherapy in PBC reported significant reduction of ALP in the treatment group compared to placebo.

Areas covered: This review covers the preclinical and clinical studies of OCA in PBC. In addition, other alternative therapies that are currently being examined in PBC patients will also be discussed in this review. A literature search was carried out using the PubMed database.

Expert opinion: If approved by the U.S. FDA, OCA will likely be an important alternative add-on therapy in PBC patients who have inadequate response to UDCA.     

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.     

熊去氧胆酸胶囊联合金玉排石汤预防十二指肠乳头切开术后结石复发

目的 观察熊去氧胆酸胶囊联合中药在防治十二指肠乳头切开术后结石复发中的作用.方法 选择1999年1月至2009年10月间在我院消化内科行十二指肠乳头切开术治疗胆管结石的患者210例,完全随机分为4组,联合用药组(55例)血脂(3.40±0.34) mmol/L;单纯口服熊去氧胆酸胶囊组(50例)血脂(4.17±0.29) mmol/L;单纯口服中药组(50例)血脂(4.02 ±0.15) mmol/L;对照组(55例)血脂(3.76±0.26) mmol/L.联合用药组低脂饮食同时加服熊去氧胆酸胶囊,10mg/(kg·d),口服,2次/d,金玉排石汤100ml,2次/d,服用半年.单纯口服熊去氧胆酸胶囊组,低脂饮食加熊去氧胆酸胶囊,10mg/( kg·d),口服,2次/d,服用半年.单纯口服中药组,低脂饮食加金玉排石汤,100ml,2次/d,服用半年.对照组,给予低脂饮食.随访半年,每6个月行上腹部B超,比较复发率.结果 联合用药组结石复发1例,复发率为1.8％;单纯服用熊去氧胆酸胶囊结石复发8例,复发率为16.0％;单纯口服中药组结石复发8例,复发率16.0％,对照组复发19例,复发率为34.5％,联合用药组复发率明显低于对照组、单纯口服中药组和单纯口服熊去氧胆酸胶囊组,差异有统计学意义(均P＜0.05).结论 服用熊去氧胆酸胶囊联合中药可有效预防结石的复发,熊去氧胆酸胶囊降低血清胆固醇水平及中药利胆排石可能是其预防复发的机制之一.     

Emerging drugs for the treatment of Primary Biliary Cholangitis

Introduction: Primary biliary cholangitis (PBC) is an autoimmune chronic disease of the liver that can progress to cirrhosis and hepatocellular carcinoma. It affects approximately 1 in 4,000 with a 10:1 female to male ratio. The diagnosis of PBC can be made based on serum antimitochondrial antibodies (AMA) in a patient with abnormally high serum alkaline phosphatase after ruling out other causes of cholestasis and biliary obstruction. Genome-wide association studies have revealed several human leukocyte antigen (HLA) and non-HLA risk loci in PBC, and complex environmental-host immunogenetic interactions are believed to underlie the etiopathogenesis of the disease. Fatigue and pruritus are the most common and often problematic symptoms; although often mild, these can be severe and life-alternating in a subset of patients. Ursodeoxycholic acid (UDCA) is the only drug approved by the United States Food and Drug Administration for the treatment of PBC. Clinical trials have shown that UDCA significantly improves transplant-free survival. However, nearly 40% of PBC patients do not respond adequately to PBC and are at higher risk for serious complications when compared to PBC patients with complete response to UDCA.

Areas Covered: Here we provide a detailed discussion regarding novel therapeutic agents and potential areas for further investigation in PBC-related research.

Expert Opinion: Results of ongoing clinical trials and emerging treatment paradigms for PBC will likely further improve medical management of this disorder in the near future.     

Ten-year combination treatment with colchicine and ursodeoxycholic acid for primary biliary cirrhosis: a double-blind, placebo-controlled trial on symptomatic patients

BACKGROUND: Combined medical treatment may provide further benefit to primary biliary cirrhosis (PBC) patients administered ursodeoxycholic acid (UDCA). AIM: To evaluate the long-term effects of colchicine and UDCA in symptomatic PBC patients. PATIENTS/METHODS: We extended up to 10 years the double-blind treatment of 44 symptomatic PBC patients originally included in a 3-year multicentre study comparing UDCA and colchicine (U + C) versus UDCA and placebo (U + P). Outcome measures were death or liver transplantation; incidence of clinically relevant events; clinical and quantitative variables retaining prognostic information. RESULTS: Mean follow-up was 7 +/- 3 years. One patient was lost, three withdrew because of jaundice (U + P); two patients stopped colchicine but remained on UDCA. Eleven patients (two for liver-unrelated reasons, U + P) and six patients (U + C) died, three and two patients, respectively, were transplanted (incidence rate difference, five cases per 100 patient-years; 95% CI, -1 to 11). Hepatocellular carcinoma developed in one (U + P) and four (U + C) patients (difference, -2; CI, -5 to 1), portal hypertension complications in nine patients from each group (difference, 1; CI, -5 to 6). Trends of serum bilirubin, Mayo score, antipyrine clearance were similar among treatment groups. CONCLUSIONS: In cirrhotic PBC patients, colchicine does not offer additional benefits to UDCA. In this population, UDCA does not obviate disease progression.     

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.     

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.     

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.     

自身免疫性肝炎-原发性胆汁性肝硬化重叠综合征12例临床分析

目的初步探讨自身免疫性肝炎和原发性胆汁性肝硬化重叠综合征（AIH-PBC OLS）的临床特点。方法回顾性总结北京军区总医院近10年收治12例AIH-PBC临床表现、血清生化指标和免疫指标以及病理及治疗。结果 AIH-PBC OLS临床表现缺乏特异性,主要有乏力、低热、黄疸、皮肤瘙痒等;肝脏酶学指标ALT、AST、ALP、GGT、IgM、IgG均明显升高,肝穿刺病理也显示肝细胞坏死、汇管区炎细胞浸润,同时可见小胆管损伤。治疗上倾向以UDCA与皮质激素或免疫抑制剂联合用药。结论 AIH-PBC OLS不完全等同于典型的AIH或者PBC,而更像是两种疾病的同时叠加,临床应严密监控,随时调整治疗方案。     

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。