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抗着丝点抗体对原发性胆汁性胆管炎患者临床特征及预后的影响
DOI: 10.12449/JCH250512
伦理学声明：本研究方案经由首都医科大学附属北京地坛医院伦理委员会审批，批号：京地伦研字［2024］第（006）-01号。
利益冲突声明：本文不存在任何利益冲突。
作者贡献声明：赫晟竹负责病例收集及数据整理，统计分析，撰写论文；刘亚兴、乔可欣、李斌协助完成病例收集；周桂琴、王宪波、冯颖负责拟定写作思路；周桂琴负责指导撰写文章，修改论文并最后定稿。
Impact of anticentromere antibody on the clinical features and prognosis of patients with primary biliary cholangitis
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摘要:
目的 通过比较抗着丝点抗体（ACA）阳性与ACA阴性原发性胆汁性胆管炎（PBC）患者在临床分型、熊去氧胆酸（UDCA）应答、GLOBE评分和UK-PBC评分的差异，分析ACA对PBC患者临床特征及预后评估的影响。 方法 选取首都医科大学附属北京地坛医院2013年8月—2022年12月入院诊断为PBC的住院患者749例，分为ACA阳性组（n=147）和ACA阴性组（n=602）。根据入院情况，按照慢性进展型、门静脉高压型和黄疸/肝衰竭型标准分型，比较两组临床分型分布差异。随访1年后资料完整的患者共261例，其中ACA阳性者53例，ACA阴性者208例，对其进行统计分析，并根据性别、年龄按照1∶2比例进行倾向性评分匹配，分别比较匹配前后两组患者1年UDCA应答率、GLOBE评分及UK-PBC评分是否存在差异。计量资料两组间比较采用成组t检验或Mann-Whitney U检验。计数资料两组间比较采用χ2检验。 结果 749例PBC患者中，ACA阳性组年龄［（61.28±10.35）岁 vs （56.74±12.17）岁，t=4.164，P<0.001］、女性患者占比（93.9% vs 77.6%，χ2=20.221，P<0.001）及门静脉高压型占比（48.3% vs 27.6%，χ2=23.289，P<0.001）均明显高于ACA阴性组，黄疸/肝衰竭型占比（24.5% vs 38.5%，χ2=10.205，P<0.001）明显低于ACA阴性组。随访1年后，资料完整的261例PBC患者倾向性评分匹配前，ACA阳性组UDCA应答率为41.5%，ACA阴性组UDCA应答率为41.8%，两组差异无统计学意义（P>0.05）；ACA阳性组GLOBE评分>0.3分者占比为92.5%，ACA阴性组为80.3%，两组差异有统计学意义（χ2=3.935，P=0.047）。倾向性评分匹配后，ACA阳性组53例，ACA阴性组106例，两组UDCA应答率、GLOBE评分及UK-PBC评分比较，差异均无统计学意义（P值均>0.05）。 结论 ACA阳性患者年龄更大，女性占比更多，且更易出现门静脉高压，黄疸/肝衰竭型相对较少。ACA阳性对UDCA应答率、GLOBE评分及UK-PBC评分无显著影响。 Abstract:Objective To investigate the impact of anticentromere antibody （ACA） on the clinical features and prognosis of patients with primary biliary cholangitis （PBC） by comparing clinical classification， ursodeoxycholic acid （UDCA） response， GLOBE score， and UK-PBC score between ACA-positive PBC patients and ACA-negative PBC patients. Methods A total of 749 patients who were admitted to Beijing Ditan Hospital， Capital Medical University， from August 2013 to December 2022 and were diagnosed with PBC were enrolled and divided into ACA-positive group with 147 patients and ACA-negative group with 602 patients. According to their conditions on admission， the two groups were compared in terms of the distribution of clinical types， i.e.， chronic progression-type PBC， portal hypertension-type PBC， and standard jaundice/liver failure-type PBC. There were 261 patients with complete data after 1-year follow-up， among whom there were 53 patients with positive ACA and 208 with negative ACA. A statistical analysis was performed， and propensity score matching was performed based on sex and age at a ratio of 1∶2. The two groups were compared in terms of 1-year UDCA response rate， GLOBE score， and UK-PBC score before and after matching. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. Results Compared with the ACA-negative group， the ACA-positive group had a significantly higher age （61.28±10.35 years vs 56.74±12.17 years， t=4.164， P<0.001）， a significantly higher proportion of female patients （93.9% vs 77.6%， χ2=20.221， P<0.001）， a significantly higher proportion of patients with portal hypertension （48.3% vs 27.6%， χ2=23.289， P<0.001）， and a significantly lower proportion of patients with jaundice/liver failure （24.5% vs 38.5%， χ2=10.205， P<0.001）. After 1-year follow-up， for the 261 PBC patients with complete data， there was no significant difference in UDCA response rate before propensity score matching between the ACA-positive group and the ACA-negative group （41.5% vs 41.8%， P>0.05）， and there was a significant difference in the proportion of patients with a GLOBE score of >0.3 between the ACA-positive group and the ACA-negative group （92.5% vs 80.3%， χ2=3.935， P=0.047）. There were 53 patients in the ACA-positive group and 106 patients in the ACA-negative group after propensity score matching， and there were no significant differences between the two groups in UDCA response rate， GLOBE score， and UK-PBC score （all P>0.05）. Conclusion ACA-positive patients tend to have an older age， with a higher proportion of female patients or patients with portal hypertension， while there is a relatively low proportion of patients with jaundice/liver failure. Positive ACA has no significant impact on UDCA response rate， GLOBE score， and UK-PBC score. -
Key words:
- Primary Biliary Cirrhosis /
- Anticentromere Antibodies /
- Signs and Symptoms /
- Prognosis
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表 1 ACA阳性与ACA阴性患者一般资料及自身抗体比较
Table 1. Comparison of general information and autoantibody between ACA positive and ACA negative groups of patients
项目 ACA阳性
（n=147）
ACA阴性
（n=602）
统计值 P值 性别［例（%）］ χ2=20.221 <0.001 男 9（6.1） 135（22.4） 女 138（93.9） 467（77.6） 年龄（岁） 61.28±10.35 56.74±12.17 t=4.164 <0.001 ANA［例（%）］ χ2=0.603 0.437 阴性 144（98.0） 578（96.0） 阳性 3（2.0） 24（4.0） AMA-M2［例（%）］ χ2=0.215 0.643 阴性 48（32.7） 185（30.7） 阳性 99（67.3） 417（69.3） 
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表 2 ACA阳性及ACA阴性患者临床分型比较
Table 2. Comparison of clinical types between ACA positive and ACA negative groups of patients
分型 ACA阳性
（n=147）
ACA阴性
（n=602）
χ2值 P值 慢性进展型［例（%）］ 40（27.2） 204（33.9） 2.320 0.128 门静脉高压型［例（%）］ 71（48.3） 166（27.6） 23.289 <0.001 黄疸/肝衰竭型［例（%）］ 36（24.5） 232（38.5） 10.205 <0.001
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表 3 匹配前ACA阳性与阴性患者UDCA应答情况及预后评分比较
Table 3. Comparison of UDCA response and prognostic scores between ACA positive and ACA negative patients before matching
项目 ACA阳性（n=53） ACA阴性（n=208） 统计值 P值 UDCA应答［例（%）］ 22（41.5） 87（41.8） χ2=0.009 0.924 GLOBE评分（分） 1.391（0.667～2.320） 1.387（0.484～2.380） Z=-0.477 0.633 GLOBE评分>0.3分［例（%）］ 49（92.5） 167（80.3） χ2=3.935 0.047 UK-PBC评分（分） 5年 0.039（0.018～0.105） 0.055（0.021～0.138） Z=-1.170 0.242 10年 0.126（0.059～0.311） 0.172（0.070～0.392） Z=-1.141 0.254 15年 0.222（0.107～0.500） 0.296（0.127～0.604） Z=-1.119 0.263
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表 4 匹配后ACA阳性与ACA阴性患者一般资料比较
Table 4. Comparison of general information between ACA positive and ACA negative groups of patients after matching
项目 ACA阳性
（n=53）
ACA阴性
（n=106）
统计值 P值 性别［例（%）］ χ2=0.412 0.521 男 4（7.5） 6（5.7） 女 49（92.5） 100（94.3） 年龄（岁） 62.42±9.98 60.85±9.68 t=-0.949 0.344
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表 5 匹配后ACA阳性与阴性患者UDCA应答情况及预后评分比较
Table 5. Comparison of UDCA response and prognostic scores between ACA positive and ACA negative patients after matching
项目 ACA阳性（n=53） ACA阴性（n=106） 统计值 P值 UDCA应答［例（%）］ 22（41.5） 43（40.6） χ2=0.123 0.725 GLOBE评分（分） 1.391（0.667～2.320） 1.741（0.670～2.525） Z=-0.622 0.534 GLOBE评分>0.3分［例（%）］ 49（92.5） 95（89.6） χ2=0.333 0.564 UK-PBC评分（分） 5年 0.039（0.018～0.105） 0.061（0.023～0.152） Z=-1.167 0.106 10年 0.126（0.059～0.311） 0.190（0.075～0.424） Z=-1.632 0.103 15年 0.222（0.107～0.500） 0.324（0.137～0.642） Z=-1.722 0.101
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