拉米夫定治疗慢性乙型肝炎病人的长期疗效

通过多中心，承机，双盲，安慰剂对照的临床试验，研究拉米夫定（ｌａｍｉｖｕｄｉｎｅ）对慢性乙型肝炎（乙肝）病人的疗效和安全性。方法随机选择３２２例慢性乙肝病拉米夫定治疗（１００ｍｇ／ｄ），１０７例病人服用安慰剂作对照，共治疗１２周，在１２周治疗结束后，拉米夫定组和安慰剂组病人均继续服用拉米夫定１００ｍｇ治疗至５２周。疗效评估包括临床症状和体征，肝功能和ＨＢＶ复制指标。结果治疗１２周，拉米夫定组ＨＢＶ

Long-term effect of lamivudine treatment in chronic hepatitis B virus infection

OBJECTIVE: To evaluate the long-term 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 with multi-center, randomized, double blind and placebo controlled trial. METHOD: 429 patients with chronic HBV infection as defined by positive HBsAg, HBeAg and HBV DNA were enrolled and randomized into lamivudine and placebo groups. 322 patients received lamivudine 100 mg daily and 107 patients received placebo treatment for 12 weeks. Then, all patients were offered a further 40 weeks of open label lamivudine treatment. The efficacy and safety were evaluated with clinical, biochemical, hematological and virological parameters. RESULTS: After 12 weeks treatment, HBV DNA response (serum HBV DNA < 1.6 ng/L) rate in lamivudine group was higher than in placebo group (92.2% VS 14.1%, P < 0.01); but at week 52, there was no difference between lamivudine and placebo/lamivudine groups (71.0% VS 77.7%, P > 0.05). Rate of HBV DNA breakthrough in lamivudine group was higher than in placebo/lamivudine group (24.4% VS 8.5%, P < 0.01). Proportion of HBeAg/anti-HBe seroconversion had no difference in two groups (7.5% VS 5.2%, P > 0.05). By week 12, ALT normalization rate in lamivudine group was higher than in placebo group (60.3% VS 27.5%, P < 0.01); but after 52 weeks treatment, there was no difference between two groups (70.9% VS 74.5%, P > 0.05). At week 48, HBV YMDD mutation rate in lamivudine group was higher than in placebo/lamivudine group (14.6% VS 5.0%, P < 0.05). The incidence of adverse events was similar for both lamivudine and placebo/lamivudine group up to week 12 and 52. There was few severe drug-related adverse event. CONCLUSION: Sustained HBV replication suppression could be obtained from long-term treatment with lamivudine 100 mg daily accompanied with good tolerance and safety.