Ursodeoxycholic acid therapy and the risk of colorectal adenoma in patients with primary biliary cirrhosis: An observational study
Ursodeoxycholic acid therapy and the risk of colorectal adenoma in patients with primary biliary cirrhosis: An observational study
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DOI：
10.1053/jhep.2003.50311
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发表时间：
2003-07-01
期刊：
影响因子：
13.5
通讯作者：
Poupon, R
中科院分区：
文献类型：
--
作者：
Serfaty, L;De Leusse, A;Poupon, R
熊去氧胆酸（UDCA）是原发性胆汁性肝硬化（PBC）的一线治疗药物。UDCA长期给药可能通过增加次级胆汁酸的粪便排泄间接促进结肠癌发生，或者相反，它可能抑制结肠癌发生，如动物模型所示。在PBC患者中，我们研究了UDCA长期给药对结直肠腺瘤患病率和复发以及结肠上皮细胞增殖的影响。114例PBC患者（103例女性，11例男性;平均年龄55岁）参加了结肠镜监测计划。比较了在结肠镜检查时已接受UDCA治疗（平均持续时间46个月）的患者（治疗组，n = 52）和在治疗开始前接受结肠镜检查的患者（未治疗组，n = 62）的结肠腺瘤患病率。比较UDCA治疗患者与从205例接受息肉切除术患者队列中选择的适当年龄和性别匹配的对照组（2/1）切除后腺瘤复发（平均随访，35个月）。使用抗M67抗体对来自治疗和未治疗患者的结肠活组织检查评估上皮细胞增殖。治疗和未治疗的患者显示出相似的人口统计学特征。治疗组结直肠腺瘤的患病率为13%，而未治疗组为24%（P = 0.16）。结肠上皮细胞增殖指数显着低于治疗患者比未经治疗的患者（P = 0.001）。切除腺瘤后，UDCA治疗患者的复发概率显著低于对照组（3年时7% vs. 28%，P = 0.04）。总之，本研究表明，在PBC患者中，UDCA长期给药（1）与结直肠腺瘤患病率增加无关，（2）显著降低结直肠腺瘤切除后复发的概率。在接受UDCA治疗的患者中观察到结肠上皮细胞增殖显著减少，从而加强了这些结果。
Ursodeoxycholic acid (UDCA) is the first-line treatment for primary biliary cirrhosis (PBC). The long-term administration of UDCA might indirectly favor colon carcinogenesis by increasing the fecal excretion of secondary bile acids or, in contrast, it might inhibit colon carcinogenesis, as demonstrated in animal models. In patients with PBC, we examined the effect of prolonged UDCA administration on the prevalence and recurrence of colorectal adenoma and on the proliferation of colon epithelial cells. One hundred fourteen patients (103 women, 11 men; mean age, 55 years) with PBC, were enrolled in a colonoscopic surveillance program. The prevalence of colon adenoma was compared in patients already treated with UDCA (mean duration 46 months) at the time of colonoscopy (treated group, n = 52) and in patients undergoing colonoscopy just prior to treatment initiation (untreated group, n = 62). The recurrence of adenoma following removal (mean follow-up, 35 months) was compared between UDCA-treated patients and appropriate age- and gender-matched controls (2/1) selected from a cohort of 205 patients undergoing polypectomy. Epithelial cell proliferation was assessed using anti-M67 antibodies on colon biopsies from both treated and untreated patients. Treated and untreated patients displayed similar demographic characteristics. The prevalence of colorectal adenomas was 13% in the treated group versus 24% in the untreated group (P = .16). The colon epithelial cell proliferation index was significantly lower in treated patients than in untreated patients (P = .001). Following removal of the adenoma, the probability of recurrence was significantly lower in patients treated with UDCA than in controls (7% vs. 28% at 3 years, P = .04). In conclusion, this study suggests that, in patients with PBC, the prolonged administration of UDCA (1) is not associated with an increased prevalence of colorectal adenomas, and (2) significantly decreases the probability of colorectal adenoma recurrence following removal. These results are strengthened by the significant reduction in colon epithelial cell proliferation seen in patients treated with UDCA.