熊去氧胆酸及其联合激素和免疫抑制剂治疗原发性胆汁性肝硬化的临床观察  

Clinical observation of the therapeutic responses of primary biliary cirrhosis

作　　者：石运莹[1,2] 史旭华[1] 费允云[1] 张烜[1] 张奉春[1] 

机构地区：[1]中国医学科学院北京协和医院风湿免疫科,100032 [2]四川大学华西医院肾脏内科

出　　处：《中华风湿病学杂志》2011年第2期91-96,共6页Chinese Journal of Rheumatology

基　　金：国家“十一五”科技支撑计划项目（2008BAI59803）

摘　　要：目的 观察熊去氧胆酸（UDGA）、UDCA联合泼尼松龙、UDCA联合硫唑嘌呤3种方案治疗对原发性胆汁性肝硬化（PBC）的疗效，并评价影响疗效的危险因素。方法 82例初诊PBC患者随机分为单用UDCA（U组，28例）、UDCA联合泼尼松龙（UP组，27例）、UDCA联合硫唑嘌呤（UA组，27例）3个治疗组，在治疗第0、3、6、12个月采集临床、实验室资料及药物不良反应。主要采用重复测量的方差分析和COX回归进行统计学处理。结果 UP组患者较U组及UA组在乏力和瘙痒程度上有明显改善（P=0．015和P=0．037），U组、UA组无改善。3组患者治疗后丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、碱性磷酸酶（ALP）、谷氨酰转肽酶（GGT）、总胆红素、直接胆红素（DBIL）和lgM均下降，组内比较差异有统计学意义（P〈0．05），3组间比较差异无统计学意义（P〉O．05）。发生疾病进展的患者Mayo危险性评分高（P=0．018）、凝血酶原时间（PT）延长（P=0．042）。UP组血糖升高2例、满月脸5例、多毛1例；UA组白细胞下降2例，胆绞痛1例，U组未出现药物不良反应。ALP、GGT、总胆固醇基线水平高是生化缓解的危险因素（P=0．015）。总胆红素、DBIL、总胆汁酸增高、PT延长不利于肝生化缓解（P=0．075）。结论 3种方案对PBC患者肝脏生化指标、lgM的改善作用相近，UDCA联合泼尼松龙方案可减轻乏力、瘙痒症状，单用UDCA方案不良反应发生率最低。Mavo危险性评分高、盯延长的患者疾病易进展；高水平的ALP、GGT、总胆固醇是生化缓解的危险因素；高水平的总胆红素、DBIL、总胆汁酸、PT不利于生化缓解。Objective The aims of this study were to compare the clinical and laboratory responses to ursodeoxycholic acid （UDCA） monotherapy with the combination therapy of UDCA plus prednisolone/azathioprine in primary biliary cirrhosis （PBC）, and to investigate the risk factors affecting the therapeutic responses. Methods Eighty-two patients with untreated PBC were divided randomly into three groups. Group U （28 patients） received UDCA alone, group UP （27 patients） received UDCA and prednisolone, while group UA （27 patients） received UDCA and azathioprine. The clinical and laboratory data were recorded after treated for 3, 6 and 12 months. Repeated measures ANOVA and COX regression model were used for statistical analysis. Results Fatigue and pruritus were improved only in group UP （P=0.015 and P=0.037 respectively）. Alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, alkaline phosphatase （ALP）, gamma-glutamyl transferase （GGT）, total bilirubin （TBIL）, direct bilirubin （DBIL） and IgM in the 3 groups were decreased （P〈0.05）, while there was no statistical significant difference between the three groups （P〉0.05）. The patients with disease progression had higher Mayo risk score （MRS） （P=0.018） and prolonged prothrombin time （PT） （P=0.042）. In group UP, side-effect associated with glueocortieosteroids occurred in eight patients while there was no side-effect in group U. High baseline levels of ALP,GGT and CHO were risk factors for biochemical remission （P=0.015）. The increase of DBIL, TBIL, total bile acid （TBA） and PT did not contribute to the prediction of biochemical remission （P=0.075）. Conclusion There are no differences among the three groups in the improvement of hepatic biochemical data and IgM. The combination therapy of UDCA with prednisolone could relieve fatigue and itching. The disease of patients with higher Mayo risk score and prolonged PT tend to progress. High baseline levels of ALP, GGT and CHO are risk fact

关 键 词：肝硬化 胆汁性 熊脱氧胆酸 泼尼松龙 硫唑嘌呤 

分 类 号：R575.2[医药卫生—消化系统]