拉米夫定治疗HBV DNA阳性慢性重型乙型肝炎疗效分析

Therapy and effciency of lamivudine in HBV-infected patients positive for serum HBV DNA positive

目的为了阻断HBV诱导的免疫性肝损伤、提高慢性重型肝炎患者的存活率,我们采用拉米夫定治疗血清HBV DNA阳性的慢性重型乙型肝炎患者,观察治疗效果与不良反应发生情况。方法 106例慢性重型乙型肝炎患者,入院时血清HBVDNA阳性而其它肝炎病毒血清学指标阴性,并排除妊娠性和酒精性肝病。随机分为A、B两组,A组在护肝、促进肝细胞再生、降酶、利胆等一般综合疗法的基础上加服拉米夫定100mg,每晚1次,不再使用其它抗病毒药物;B组仅采用一般综合疗法。两组患者住院日均大于30d,观察疗程均为1年,治疗中肝功能恢复后又出现异常者为肝炎再活动。所有病例入院时、入院后每月定期采血用ELISA法检测HBVM,荧光定量PCR法检测HBV DNA;同时观察血清总胆红素、血常规及甲胎蛋白等指标。结果 A组患者存活率为67.9％(36/53),与B组(49.1％,26/53)比较具有显著性差异(P<0.05)。存活患者中,A组HBeAg、HBV DNA阳性率分别为25.0％(9/36)、5.6％(2/36),B组分别为61.5％(16/26)、84.6％(22/26),两组差异有高度显著性(P均<0.01);A组血清HBV DNA阳性者的HBVDNA平均含量(103.8±126.0 copy/μl)也显著低于B组(5 196.4±2 353.8 copy/μl)(P<0.01),两者与入院时(3 944.7±859.6 copy/μl)比较,差异均有高度显著性(P<0.01)。A组TBiL复常时间(98.5±21.3d)比B组(124.7±32.0d)明显缩短(P<0.01),1年后肝炎再活动率(13.9％,5/36)明显低于B组(65.4％,17/26)(P<0.01)。A组中仅个别患者出现轻度腹泻,未见血常规和甲胎蛋白检测异常。结论拉米夫定能够抑制HBV DNA合成,减少新表达的靶抗原量,使炎症反应逐渐缓解。本研究发现,应用拉米夫定治疗血清HBV DNA阳性的慢性重型乙型肝炎,可促使HBeAg和HBV DNA转阴,且血清HBV DNA未转阴者的HBV DNA平均含量也显著低于对照病例与自身治疗前水平,说明患者体内HBV DNA的复制受到抑制。相反,对照病例经一般综合治疗后血清HBV DNA阳性者的HBV DNA平均含量不仅明显高于拉米夫定治疗患者,还明显高于自身治疗前水平,表明未采用拉米夫定治疗患者体内仍存在HBV DNA大量复制。我们还观察到经拉米夫定治疗后,患者TBiL复常时间明显缩短,肝炎再活动率也明显降低,说明拉米夫定能够促进肝功能的恢复、减少肝炎的复发。此外,拉米夫定副作用少见,对造血系统和肝细胞增生无明显抑制作用。上述机制可能与本研究中采用拉米夫定治疗时患者生存率较高有关。本研究证明:拉米夫定是治疗慢性重型乙型肝炎、抗HBV的安全有效药物。

To observe the efficiency and safety of lamivudine in the treatment of chronic severe hepatitis B with HBV DAN positive in serum. Methods In this series, 106 cases of chronic severe hepatitis B with serum HBV DNA positive were randomly divided into groups A and B. Patients in group A received ordinary synthetic treatment plus lamivudine, and ones in group B received the ordinary synthetic treatment only. The survivals were observed for one year from the begin- ning of the treatment. Results The survival rate in group A (67.9%, 36/53) was higher than that in group B (49.1%, 26/5) (P<0.05). Among the survivals, the positive rates of serum HBeAg and HBV DNA in group A were found to be much lower than that in group B (25. 0%, 9/36 vs 61. 5%, 16/26 and 5. 6%, 2/36 vs 84. 6%, 22/26, respectively) (P <0. 01 ); The time for serum total bilirubin back to normal was significantly shorter and the reactivity rate of hepatitis was obvi- ously lower in group A (98.5± 21. 3 days and 13. 9%, 5/36, respectively) than in group B (124.7 ± 32.0 days and 65.4%, 17/26, respectively) (P< 0.01 ). There were few cases who had slight diarrhea and none was found to be abnormal in rou- tine blood test and α-fetoprotein detection test. Conclusion As a anti-HBV drug, Lamivudine is safety and efficacy in the treatment of chronic severe hepatitis B. It can increase the sur- vival rate of the patients by inhibiting HBV DNA replication, improving the liver function and reducing the relapse of the dis- ease.