拉米夫定联合疗肝3号对乙型肝炎病毒YMDD变异的影响及机制分析

Lamivudine in combination with Liaogansanhao in treatment of patients with chronic hepatitis B and its effects on YMDD variants

目的观察拉米夫定联合疗肝3号对乙型肝炎病毒YMDD变异的影响。方法将80例慢性乙型肝炎(CHB)患者随机分为治疗组和对照组,治疗组40例为联合应用拉米夫定和疗肝3号;对照组40例为单用拉米夫定,疗程均为18个月,每3个月分别检测肝功能、乙型肝炎病毒血清学标志物、HBV DNA、YMDD变异株、T淋巴细胞亚群。结果在治疗12个月时,治疗组出现2例(5.00%)变异,对照组5例(12.50%),差异无显著性(P>0.05);在治疗18个月时,治疗组出现4例(10.00%)变异,对照组12例(30.00%),差异有显著性(P<0.05)。停药6个月后治疗组在HBV-DNA阴转、HBeAg/抗-HBe血清转换、HBeAg阴转上明显优于对照组(P均<0.05)。治疗组外周血CD4+亚群水平上调,CD4+/CD8+比值趋于正常,停药6个月后仍持续保持高水平,与对照组比较差异有高度显著性(P均<0.01)。结论拉米夫定联合疗肝3号有调节CHB患者细胞免疫水平的作用,可减少YMDD变异的发生。

Objective To observe the effects with lamivudine in treatment of patients with chronic of traditional Chinese medicine Liaogansanhao in combination hepatitis B （CHB） and its effects on YMDD variants Methods 80 patients were enrolled and randomized into two groups： the treated group of 40 cases, treated with Liaogansanhao in combination with lamivudine; the control group of 40 cases, treated with lamivudine alone. One cycle lasted for 18 months, every 3 months, the liver function, virological markers of HBV, serum HBV DNA, YMDD variants and T - cell subpopulation were determined. Results At the end of 12 - month treatment, 2 cases （5.00 % ） in the treated group and 5 cases （12.50 % ） in the control group with YMDD variants were observed, there was no statistical difference （ P 〈 0.05）. At the end of 18 - month treatment, 4 cases （ 10.00 % ） with YMDD variants were observed in the treated grup and was significantly less than the control group, 12 cases （30.00%）, P 〈 0.05. Six months after treatment, HBV - DNA - negative rate, HbeAg/anti - HBe negative and HBeAg negative rate in the treated group were superior to the control group （all P 〈0.01）. In the treated group, the CD4^＋ level was up - regulated and the ratio of CD4^＋/CD8^＋ tended to be in a normal level, and 6 months after the treatment the level remained in a high level, and was significantly higher than the control group （all P 〈0.01）. Conclusion Liao-gansanhao in combination with lamivudine may up - regulate the cell immunological level in patients with CHB, which may reduce the occurrence of YMDD.