Gong Yan, Huang Zhi Bi, Christensen Erik, Gluud Christian
Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 3344, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, Copenhagen N, Denmark, 2200.
Cochrane Database Syst Rev. 2008 Jul 16(3):CD000551. doi: 10.1002/14651858.CD000551.pub2.
Primary biliary cirrhosis is an uncommon autoimmune liver disease with unknown aetiology. Ursodeoxycholic acid (UDCA) has been used for primary biliary cirrhosis, but the effects remain controversial.
To evaluate the benefits and harms of UDCA on patients with primary biliary cirrhosis against placebo or no intervention.
We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials on The Cochrane Library, MEDLINE, EMBASE, SCI-EXPANDED, The Chinese Biomedical CD Database, LILACS, and the references of identified studies. The last search was performed in January 2007.
Randomised clinical trials evaluating UDCA versus placebo or no intervention in patients with primary biliary cirrhosis.
The primary outcomes were mortality and mortality or liver transplantation. Binary outcomes were reported as odds ratio (OR) or relative risk (RR) and continuous outcomes as weighted mean difference, all with 95% confidence intervals (CI). Meta-regression was used to investigate the associations between UDCA effects and quality of the trial, UDCA dose, trial duration, and patient's severity of primary biliary cirrhosis. We also used Bayesian meta-analytic approach to estimate the UDCA effect as sensitivity analysis.
Sixteen randomised clinical trials evaluating UDCA against placebo or no intervention were identified. Data from three trials have been updated. Nearly half of the trials had high risk of bias. The combined results demonstrated no significant effects favouring UDCA on mortality (OR 0.97, 95% CI 0.67 to 1.42) and mortality or liver transplantation (RR 0.92, 95% CI 0.71 to 1.21). The findings were supported by the Bayesian meta-analyses. UDCA did not improve pruritus, fatigue, autoimmune conditions, liver histology, or portal pressure. UDCA seemed to improve biochemical variables, like serum bilirubin, ascites, and jaundice, but the findings were based on few trials with sparse data. The use of UDCA is significantly associated with adverse events, mainly weight gain.
AUTHORS' CONCLUSIONS: This systematic review did not demonstrate any benefit of UDCA on mortality and mortality or liver transplantation of patients with primary biliary cirrhosis. The few beneficial effects could not be due to random errors or outcome reporting bias.
原发性胆汁性肝硬化是一种病因不明的罕见自身免疫性肝病。熊去氧胆酸（UDCA）已被用于治疗原发性胆汁性肝硬化，但其效果仍存在争议。
评估熊去氧胆酸对比安慰剂或不进行干预对原发性胆汁性肝硬化患者的利弊。
我们检索了Cochrane肝胆组对照试验注册库、Cochrane图书馆中的Cochrane对照试验中央注册库、医学文献数据库、EMBASE、科学引文索引扩展版、中国生物医学光盘数据库、拉丁美洲及加勒比地区卫生科学数据库以及已识别研究的参考文献。最后一次检索于2007年1月进行。
评估熊去氧胆酸对比安慰剂或不进行干预治疗原发性胆汁性肝硬化患者的随机临床试验。
主要结局为死亡率以及死亡率或肝移植。二分类结局以比值比（OR）或相对危险度（RR）报告，连续性结局以加权均数差报告，均给出95%置信区间（CI）。采用Meta回归研究熊去氧胆酸疗效与试验质量、熊去氧胆酸剂量、试验持续时间以及原发性胆汁性肝硬化患者严重程度之间的关联。我们还采用贝叶斯Meta分析方法估计熊去氧胆酸的疗效作为敏感性分析。
共识别出16项评估熊去氧胆酸对比安慰剂或不进行干预的随机临床试验。3项试验的数据已更新。近一半的试验存在高偏倚风险。综合结果显示，在死亡率（OR 0.97，95%CI 0.67至1.42）以及死亡率或肝移植方面（RR 0.92，95%CI 0.71至1.21），未发现熊去氧胆酸有显著疗效。这些结果得到了贝叶斯Meta分析的支持。熊去氧胆酸并未改善瘙痒、疲劳、自身免疫状况、肝脏组织学或门静脉压力。熊去氧胆酸似乎改善了生化指标，如血清胆红素、腹水和黄疸，但这些结果基于少数试验且数据稀少。使用熊去氧胆酸与不良事件显著相关，主要是体重增加。
本系统评价未证明熊去氧胆酸对原发性胆汁性肝硬化患者的死亡率以及死亡率或肝移植有任何益处。少数有益效果不可能是由于随机误差或结局报告偏倚所致。
