熊去氧胆酸联合糖皮质激素治疗自身免疫性肝炎-原发性胆汁性肝硬化重叠综合征的疗效观察

Observation on therapeutic alliance with UDCA and glucocorticoids in AIH-PBC overlap syndrome

目的 观察熊去氧胆酸（UDCA）联合糖皮质激素治疗自身免疫性肝炎（AIH）-原发性胆汁性肝硬化（PBC）重叠综合征的长期疗效.方法 对19例AIH-PBC重叠综合征患者根据其初始治疗方案的不同分为初始UDCA联合激素治疗组及初始UDCA单药治疗组,根据患者肝炎病理炎症（G）和纤维化（S）程度分为病理早期组（〈G2S2）和病理晚期组（〉G2S2）,回顾性分析不同时间段加用激素及不同病理分期患者的疗效、生物化学应答状况和组织病理学变化情况.治疗前后数据的比较应用配对样本的t检验（正态分布）或两配对样本的Wilcoxon非参数秩和检验（非正态分布）,生物化学应答率比较应用Fisher＇s精确检验法.结果 初始UDCA联合激素治疗组中位治疗时间为10.4（6.0～23.0）个月,治疗后ALT,AST,球蛋白、碱性磷酸酶（ALP）、γ-谷氨酰转移酶及IgG水平较治疗前明显下降（P值均〈0.05）;初始UDCA单药冶疗8.1（3.0～15.0）个月后,患者生物化学及免疫学指标变化差异无统计学意义（P值均〉0.05）,加用激素治疗10.6（6.0~24.0）个月后,ALT、AST、球蛋白,ALP及IgG水平较治疗前明显下降（P值均〈0.05）,与初始UDCA联合激素治疗组的ALT、IgG及ALP生物化学应答率差异无统计学意义（P值均〉0.05）.5例病理早期AIH-PBC重叠综合征患者出现ALT、IgG及ALP完全应答,不同病理分期患者ALT生物化学应答率差异有统计学意义（P〈0.05）.3例患者有治疗前后肝活组织病理检查结果,可见汇管区及界板内淋巴细胞及浆细胞的浸润明显减轻,纤维间隔的范围在一定程度有所减小.结论 对于诊断为AIH-PBC重叠综合征的患者,建议积极早期应用UDCA与糖皮质激素联合治疗.联合治疗对不同病理分期的患者都有疗效,但早期应用可能获得更佳的生物化学应答及组织学改善.

Objective To observe the efficacy of ursodeoxycholic acid（UDCA） combined with glucocorticoids in the treatment of autoimmune hepatitis-primary b＇fliary cirrhosis （AIH-PBC） overlap syndrome. Methods 19 patients with AIH-PBC overlap syndrome were divided randomly into two groups： initiate combined group and initiate UDCA-monotherapy group. Biochemical responses and pathological features before and after treatment were analyzed retrospectively with student＇s t test, Wilcoxon rank sum test and Fisher＇s exact method. Results In the initiate combination group, biochemical responses in terms of AIH features （ALT decline to normal, IgG ≤ 16 g/L） and PBC features （ALP decline ≥ 40% or to normal） were achieved. In UDCA-monotherapy group, no statistical difference existed in biochemical responses before adding glucocorticoids, whereas the levels of ALT, AST, GLB and IgG decreased significantly when combined with glucocorticoids. No statistical difference of rates of biochemical responses eixted between the two groups, whereas variance could be seen in different pathological stages. Alleviation of inflammatory infiltration after therapy appeared in 3 patients. Conclusion Combination therapy of UDCA with glucocorticoids could be suitable for AIH-PBC overlap syndrome. Early treatment is of benefit for achieving better biochemical response and pathological improvement.