温阳化瘀汤和拉米夫定序贯治疗慢性乙型肝炎的临床研究

Clinical study of sequential treatment with Wenyang Huayu decoction and lamivudine on patients with chronic hepatitis B

目的:观察温阳化瘀汤和拉米夫定序贯治疗免疫耐受期慢性乙型肝炎患者的临床疗效。方法:60例免疫耐受期慢性乙型肝炎患者随机分为两组,治疗组患者先用温阳化瘀汤水煎取汁,分两次口服,1剂/d;另加服百令胶囊,3次/d,5粒/次。至肝功能ALT>200U/L后再改为口服拉米夫定,1次/d,100mg次/。对照组患者仅口服拉米夫定,100mg次/,1次/d。口服拉米夫定后观察时间为6个月。观察患者血清肝功能、HBV DNA、Ⅳ-C、HA、LN、PCⅢ等指标的改善情况及治疗前后肝组织病理学的变化。结果:治疗组患者血清ALT有一个先降后升的过程,一般经过3周至3个月可达到正常值上限的5倍以上,并控制在10倍以内,患者阳虚证候明显好转,血清HA水平明显升高,肝脏炎症程度分级均值接近3级,与对照组比较差异有显著性意义(P<0.001)。口服拉米夫定6个月后治疗组患者HBeAg/HBeAb血清转换率、HBV DNA阴转率显著高于对照组;两组患者肝脏炎症程度分级均较服拉米夫定前显著下降,治疗组下降趋势更明显,但组间比较差异无显著性意义;两组患者肝纤维化各项指标检测值有下降趋势,但组间比较差异均无显著性意义。结论:温阳化瘀汤可纠正患者的免疫耐受,温阳化瘀汤联合拉米夫定序贯治疗可提高患者血清HBV标志物的阴转率,增强拉米夫定抗肝纤维化的作用。

Objective： In order to obstract the clinical effect of sequential using Wenyang Huayu decoction and lamivudine on the patients with chronic hepatitis B, which was in immune tolerance period. Methods： Totally 60 patients with chronic hepatitis B were randomly divided into two groups： 30 cases as therapy group and 30 cases as control group. The therapy group was administered Wenyang Huayu decoction, tested liver function once a week, after serum alanine aminotransferase （ALT） up to 200U/L, then retook lamivudine tablet 100mg once daily and followed-up for 6 months. The control group were only prescribed lamivudine 100mg once daily. The liver function and hepatitis B （HBV） virology including HBV DNA level, HBV marker, and hepatic fibrosis related indexes （HA, LN, PC Ⅲ, IV-C） were tested at pre-therapy with Wenyang Huayu decoction, before and after 6 months treatment with lamivudine. Pathologic examination of liver biopsy were performed before and after 6 months treatment with lamivudine. Results： After Wenyang Huayu decoction was taken for 3 weeks to 3 months, the serum ALT of the therapy group had a reduction at first, then had an improvement, up as high as 5 × ULN to 10 × ULN. When the serum ALT of the therapy group up to 5 × ULN to 10 × ULN, symptoms of lacking in vital yang had improved obviously, the HA concentration of the therapy group was improved obviously, the median of the grade of inflammation of hepatic tissue was around grade 3, and was distince different from that of the control group at pre-therapy with lamivudine. After treatment with lamivudine for 6 months, the grading scores of inflammation of hepatic tissue were decreased obviously but there was indistinct different in the two groups,the rats of undetectable HBV DNA level and HBeAg/HBeAb sero-conversion were distinct different in the two group. The hepatic fibrosis related indexes （HA, LN, PC Ⅲ,Ⅳ-C） were indistinct different in the two groups at pre-therapy, and were distinct different after 6 months treatment with lamivudine. The fibrotic stage scores were decreased at various degrees in the two groups after 6 months treatment with lamivudine, but there was indistinct different in the two groups at before and after 6 months treatment with lamivudine. Conclusion： Wenyang Huayu decoction could break immune tolerance to HBV antigen. Significant improvement of negative rat of HBV makers, HBV DNA as well as significant decrease in hepatic fibrosis related indexes （ HA, LN, PC Ⅲ, Ⅳ-C） could be obtained by sequential treatment with Wenyang Huayu decoction and lamivudine on patients with chronic hepatitis B than only by treatment with lamivudine.