熊去氧胆酸联合扶正化瘀胶囊治疗原发性胆汁性肝硬化临床观察

Clinical Observation on the Safety and Efficacy of Ursodeoxycholic Acid and Fuzheng Huayu Capsule in the Treatment of Primary Biliary Cirrhosis

目的观察熊去氧胆酸(ursodeoxycholic acid,UDCA)联合扶正化瘀胶囊治疗原发性胆汁性肝硬化(primary biliary cirrhosis,PBC)的临床疗效。方法 80例PBC患者随机分为两组,治疗组用UDCA联合扶正化瘀胶囊治疗,对照组单一UDCA治疗,疗程48周。观察两组在用药前及用药第4、12、24、48周有关指标变化,包括主要症状、体征及肝功能[ALT、AST、碱性磷酸酶(ALP)、谷氨酰转肽酶(GGT)、ALB、TBIL、TBA)]、肝纤维化指标[(血清透明质酸(HA)、层粘连蛋白(LN)、Ⅳ型胶原(Ⅳ-CL)、Ⅲ型前胶原(PⅢP)〗、免疫学指标(IgG、IgM、自身免疫性抗体)、门脉血流动力学的变化及不良反应。结果治疗后治疗组乏力及皮肤瘙痒症状明显改善,与对照组比较差异有统计学意义(P<0.05,P<0.01)。两组ALT、AST、ALP、GGT、TBIL及TBA值均明显下降,治疗组低于同期对照组(P<0.05),以第4周降幅最大;且治疗组ALB第48周较治疗前上升(P<0.05)。治疗组第4、12、24周HA、PⅢP值明显下降,第4、12周LN、Ⅳ-C值明显下降,肝纤维化指标均在第4周降幅较大,而对照组仅HA、PⅢP于第12周才低于治疗前水平。两组IgG、IgM均得到改善,治疗组优于对照组(P<0.05,P<0.01)。治疗组有1例ANA和2例AMA阴转。48周后治疗组较治疗前脾回缩,门静脉内径、脾静脉内径缩小,门静脉、脾静脉血流速度增加(P<0.01)。第24、48周,治疗组分别有82.5%、90.0%得到完全反应,均优于对照组(P<0.05)。治疗期间两组均无明显不良反应。结论 UDCA联合扶正化瘀胶囊治疗PBC抗肝纤维化及改善肝功能效果明显快速,安全性好,优于单用UDCA,主张长期联用,可能提高远期疗效。

Objective To observe the clinical efficacy of ursodeoxycholic acid （UDCA） and Fuzheng Huayu Capsule （FHC） in the treatment of primary biliary cirrhosis （PBC）. Methods Eighty PBC patients were randomly assigned to two groups, the treatment group and the control group, 40 in each group. Patients in the treatment group took UDCA and FHC, while those in the control group were treated with UDCA alone. The treatment course was 48 weeks for both groups. The clinical symptoms and signs, liver function indices （ALT, AST, ALP, GGT, ALB, TBIL, and TBA）, hepatic fibrosis indices （HA, LN, Ⅳ-CL, and P ⅢP）, immunologic indices （IgG, IgM, and autoimmune antibodies）, changes of portal hemodynamics, and adverse reactions were observed before treatment, as well as at week 4, 12, 24, and 48 after treatment. Results After treatment the skin itching and fatigue were significantly improved in the treatment group, showing statistical difference when compared with the control group （P0.05, P0.01）. After treatment the levels of ALT, AST, ALP, GGT, TBIL, and TBA obviously decreased in the two groups. They were lower in the treatment group than in the control group at the same time point （P0.05）. The decrement was the largest at week 4. Besides, at week 48 after treatment the ALB level was improved in the treatment group （P0.05）. The levels of HA and P ⅢP obviously decreased at week 4, 12, and 24, the levels of LN and Ⅳ-C obviously decreased at week 4 and 12, the decrement of the hepatic fibrosis indices at week 4 were more obvious in the treatment group. But the levels of HA and P ⅢP were lower than the pre-treatment levels at week 12 in the control group. The immunologic indices such as IgM and IgG were improved in the two groups, with better results obtained in the treatment group （P0.05, P0.01）. In the treatment group ANA turned negative in 1 patient and AMA turned negative in 2 patients. After 48 weeks of treatment, the spleen was retracted, the inner diameters of the portal vein （PV） and the splenic vein （SV） were significantly reduced, and the blood flow velocity in the PV and SV increased in the treatment group （P0.01）. At week 24 and 48, 33 patients （82.5%） and 26 patients （90.0%） in the treatment group had complete relief, better than those of the control group [22 cases （55.0%） and 28 cases （70.0%）]. No obvious adverse reaction was found in the two groups during the treatment course. Conclusions The combination therapy of UDCA and FHC was effective and safe in anti-fibrosis and improving the liver functions of PBC patients. It was safe and better than the application of UDCA alone. It was advocated to be combined use for a long term. It might improve the long-term efficacy.