拉米夫定治疗慢性乙型肝炎的多中心、随机双盲、安慰剂对照研究

目的：研究拉米夫定对血清乙型肝炎病毒＿脱氧核糖核酸（ＨＢＶ＿ＤＮＡ）阳性的慢性乙型肝炎病毒感染病人的疗效和安全性。方法：４２９例病人，随机分成拉米夫定治疗组（３２２例）和安慰剂对照组（１０７例）。治疗组每日口服拉米夫定１００ｍｇ，对照组服用外形相同的安慰剂每日１片，共１２ｗｋ。结果：治疗组累计９２．２％病人血清ＨＢＶ＿ＤＮＡ阴转（低于１．６ｎｇ／Ｌ），最终持续阴转率为７８．５％。对照组ＨＢＶ＿ＤＮＡ累计阴转率为１４．１％，最终阴转率为１１％。２组疗效比较Ｐ＜０．０１。治疗前丙氨酸转氨酶（ＡＬＴ）增高的病人，１２ｗｋ时治疗组的ＡＬＴ复常率为６０．３％，对照组为２７％，Ｐ＜０．０１。２组ＨＢｅＡｇ／抗ＨＢｅ的血清转换率差别无显著意义（Ｐ＞０．０５）。２组的不良反应发生率比较，差别无显著意义（Ｐ＞０．０５）。结论：拉米夫定能明显降低血清ＨＢＶ＿ＤＮＡ水平，促使ＡＬＴ恢复正常，不良反应轻，耐受性好。

A randomized double-blind, placebo-controlled study of lamivudine in treatment of chronic hepatitis B patients

AIM: To evaluate the effect of lamivudine on the loss of serum HBV_DNA, HBeAg/antiHBe seroconversion and ALT levels in chronic hepatitis B patients and its safety profile and tolerance compared with placebo. METHODS: Four hundred and twenty_nine patients had chronic HBV infection as defined by positive HBsAg, HBeAg and HBV_DNA were enrolled and randomized into lamivudine and placebo groups. Three hundred and twenty_two patients received lamivudine 100 mg daily and 107 patients received placebo treatment for 12 wk. The efficacy and safety were evaluated with clinical, biochemical, hematological and virological parameters. Serum specimens were collected and sent to an independent central laboratory to assay HBV_DNA quantitating and HBeAg/anti_HBe determination. RESULTS: During the 12 wk treatment period, 92.2% of lamivudine treated patients became HBV_DNA ne_ gative (below 1.6 ng/L) compared with only 14.1% of those receiving placebo ( P <0.01). At the end of 12 wk, the sustained negative for HBV_DNA in lamivudine treated group was 78.5% compared with placebo group was 11% ( P <0. 01). Patients with elevated ALT levels at baseline became normal in 60.3% of the lamivudine treated group compared with the placebo group were only 27 % were normal ( P < 0.01). Lamivudine was well tolerated in a dose of 100 mg daily and the overall incidence of adverse events was similar to placebo. Most adverse events were mild and moderate in degree and will be subside during continuing treatment. 12 patients were withdrawn from this study due to personal reason, and no patient was withdrawn due to adverse event. CONCLUSION: Lamivudine is effective in the inhibition of HBV replication indicated by the rapid loss of serum HBV_DNA and often accompanied by a decrease of serum ALT levels. Lamivudine was well tolerated without severe adverse reaction during treatment.