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[目的]探讨维生素D联合前列地尔对熊去氧胆酸应答不佳的原发性胆汁性肝硬变患者的临床疗效。[方法]选取2010年1月-2015年9月在黄石市中心医院感染科治疗的157例的原发性胆汁性肝硬化患者,采用随机数字表法分为2组,分别为常规剂量组(77例)和大剂量组(80例)13-15mg·kg~(-1)·d~(-1)、20-25mg·kg~(-1)·d~(-1)熊去氧胆酸进行治疗,疗程持续6个月。再用随机数字表的方法将熊去氧胆酸应答不佳的81例患者分为维生素D组、前列地尔组和联合组,3组均给予20~25mg·kg~(-1)·d~(-1)熊去氧胆酸治疗,27例维生素D组患者加用维生素D0.02mg/次,1次/d,27例前列地尔组加用前列地尔2ml+10ml生理盐水静脉注射,1次/d,每月治疗7d,联合组加用维生素D+前列地尔,用法用量同前2组。3组均治疗3月,观察治疗前后2组患者肝功能及T淋巴细胞亚群、细胞因子IL-2、TNF-α的变化、并比较治疗有效率和记录不良反应。[结果]常规剂量组(77例)和大剂量组(80例)对于UDCA应答不佳比较[58.4%(45/77)48.2%(39/81)],差异无统计学意义(P>0.05)。治疗后,维生素D组、前列地尔组和联合组总胆红素、谷丙转氨酸、谷草转氨酸、碱性磷酸酶和谷氨酸转移酶均降低,联合组下降程度优于另外2组,维生素D组下降程度优于前列地尔组,差异均具有统计学意义(P<0.05);治疗后,3组CD4~+水平下降,CD8~+水平上升,CD4~+/CD8~+比值下降,同时IL-2及TNF-α水平也较治疗前下降,联合组治疗后CD4~+、CD8~+、CD4~+/CD8~+、IL-2、TNF-α变化差异优于另外2组,维生素D组变化差异优于前列地尔组,差异均具有统计学意义(P<0.05);联合组的总有效率为95.2%(19/21)和维生素D组的71.4%(15/21)要高于前列地尔组47.6%(10/21),差异均具有统计学意义(P<0.05)。[结论]运用维生素D联合前列地尔治疗熊去氧胆酸应答不佳的原发性胆汁性肝硬变患者疗效良好,能够明显改善患者肝功能和免疫功能。
[Objective] To investigate the clinical efficacy of vitamin D combined with prostaglandin in patients with primary biliary cirrhosis who had poor response to ursodeoxycholic acid. [Methods] 157 patients with primary biliary cirrhosis who were treated in the Central Hospital of Huangshi from January 2010 to September 2015 were randomly divided into 2 groups: 77 cases) and high dose group (80 cases) 13-15 mg · kg -1 · d -1, 20-25 mg · kg -1 · d -1 ursodeoxycholic acid Acid for treatment, treatment duration of 6 months. 81 patients with poor response to ursodeoxycholic acid were divided into vitamin D group, alprostadil group and combination group by random number table. All the three groups were given 20 ~ 25 mg · kg -1 · d ~ (-1) ursodeoxycholic acid treatment, 27 patients with vitamin D group plus vitamin D0.02mg / time, 1 / d, 27 cases of alprostadil plus alprostadil 2ml + 10ml saline intravenously , 1 time / d, monthly treatment 7d, combined group with vitamin D + alprostadil, usage and dosage with the first two groups. Three groups were treated for 3 months. The changes of liver function, T lymphocyte subsets, cytokines IL-2 and TNF-α in two groups before and after treatment were observed. The treatment efficiency and adverse reaction were recorded. [Results] There was no significant difference between the conventional treatment group (77 cases) and the high-dose treatment group (80 cases) for the poor response to UDCA [58.4% (45/77) vs 48.2% (39/81)] 0.05). After treatment, total bilirubin, alanine, aspartate, alkaline phosphatase and glutamate transferase were decreased in the vitamin D group, the alprostadil group, and the combination group, and the degree of decrease in the combination group was superior to that of the other (P <0.05). After treatment, the level of CD4 ~ + decreased, the level of CD8 + increased, the level of CD4 ~ + / CD8 ~ + Ratio decreased and the levels of IL-2 and TNF-α also decreased compared with those before treatment. The difference of CD4 ~ +, CD8 ~ +, CD4 ~ + / CD8 ~ +, IL-2 and TNF- The other two groups, vitamin D group difference is superior to alprostadil group, the difference was statistically significant (P <0.05); combined group total effective rate was 95.2% (19/21) and vitamin D group 71.4% ( 15/21) than the alprostadil group 47.6% (10/21), the difference was statistically significant (P <0.05). [Conclusion] The combination of vitamin D and alprostadil in treatment of ursodeoxycholic acid poor response to primary biliary cirrhosis patients with good effect, can significantly improve liver function and immune function.