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目的 评价拉米夫定治疗慢性乙型肝炎的长期疗效和安全性以及YMDD变异对临床的影响。方法 这是一项多中心、随机双盲、安慰剂对照临床试验 ,始于 1996年。 4 2 9例HBsAg、HBeAg和HBVDNA阳性病人进入本研究。病人以 3∶1的比例随机接受拉米夫定 (10 0毫克 /日 ,n =32 2 )或安慰剂 (n =10 7)治疗 12周。随后所有病人接受拉米夫定开放治疗 ,每 4周随访一次 ,共 10 4周。结果 治疗一年后 72 7%病人 (2 85 / 392 )持续HBVDNA阴转。除外YMDD变异病人 ,病毒DNA在第二年持续受到抑制。YMDD变异病人血清HBVDNA的平均水平上升至 86Meq/ml (bDNA分析 ) ,但远低于治疗前水平。拉米夫定治疗可促进HBeAg消失和HBeAg/抗 HBe血清转换 ,二者均与治疗前ALT水平和治疗时间有关。第二年HBeAg消失率在治疗前ALT水平高于正常一倍的病人中为 2 6 8% ,在治疗前ALT水平高于正常二倍、五倍的病人中分别为 35 6%和 5 5 6%。HBeAg血清转换率分别为 17 4 % ,2 2 2 % ,33 3%。二年后 ,5 0 3%治疗前ALT异常的病人ALT保持正常。 83%治疗前ALT正常的病人仍保持正常。YMDD变异发生率为 4 9 7%。其血清HBVDNA中位数水平轻度升高至 86Meq/ml,其中 15 %病人ALT高于治疗前水平。 4例病人临床症状出现反复停药后恢复。拉米夫定的不良反?
Objective To evaluate the long-term efficacy and safety of lamivudine in the treatment of chronic hepatitis B and the clinical effect of YMDD mutation. Method This is a multicenter, randomized, double-blind, placebo-controlled clinical trial that began in 1996. 4 2 9 HBsAg, HBeAg and HBVDNA positive patients entered the study. Patients were randomized to receive lamivudine (10 mg / day, n = 32 2) or placebo (n = 10 7) in a 3: 1 ratio for 12 weeks. All patients subsequently received lamivudine open treatment, followed up every 4 weeks for a total of 104 weeks. Results 72.7% of patients (855/392) had persistent HBVDNA negative conversion after one year of treatment. With the exception of YMDD variant patients, viral DNA was consistently suppressed in the second year. The mean level of serum HBVDNA in patients with YMDD mutations rose to 86 Meq / ml (bDNA analysis), but well below pre-treatment levels. Lamivudine treatment promotes HBeAg loss and HBeAg / anti-HBe seroconversion, both of which are related to pretreatment ALT levels and duration of treatment. In the second year, the rate of disappearance of HBeAg was 26.8% higher in patients with pre-treatment ALT than twice their normal levels, and ALT levels were twice as high before treatment and 35.6% and 556 respectively %. HBeAg seroconversion rates were 17.4%, 22.2%, 33.3%, respectively. Two years later, ALT remained normal in 530% of patients with pre-treatment ALT abnormalities. 83% of patients with normal ALT before treatment remained normal. The incidence of YMDD mutation was 497%. The median serum HBVDNA level slightly elevated to 86Meq / ml, 15% of patients with ALT above pre-treatment levels. Four patients recovered after clinical discontinuation. Lamivudine adverse reaction?