摘要
目的通过多中心、随机、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例慢性乙肝病人用拉米夫定治疗（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１００ｍｍ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ＨＢＶＤＮＡ累计阴转率（低于１．６ｕｎ／Ｌ）和最终阴转率均显著高于安慰剂组（９２、２％对１４．１％，Ｐ＜０．０１；７８．５％对１１．１％，Ｐ＜０．０１）。第５２周末，拉米夫定治疗组的ＨＨＶ ＤＮＡ最终阴转率与安慰剂／拉米夫定对照组差异无显著性（７１．０％对７７．７％，Ｐ＞０．０到。治疗结束时，拉米夫定治疗组和安慰剂／拉米夫定对照组病人ＨＢｅＡｇ并伴有抗－ＨＢｅ阳性的血清转换率差异无显著性（７．５％对５．２％，Ｐ＞０．０５）。无１例发生ＨＢｓＡｇ阴转。第１２周时拉米夫定组ＡＬＴ的复常率高于安慰剂组（６０．３％对２７．５％，Ｐ＜０．０５）。治疗结束时，两组病人＊＊Ｔ的最终复常率差异无显著性（７０９％对７４．％，Ｐ＞０?
Objective To evaluate tile long-term effect of lamivudine on the loss of serum HBVDNA, HBeAg/antiHBe seroconversion and ALT levels in chronic hepatitis B patients and its safety profileand tolerance with multi-center, randomized, double blind and placebo controlled trial. Method 429 pa-tients with chronic HBV infection as defined by positive HBsAg, HBeAg and HBV DNA were enrolledand randomed into lamivudine and placebo groups. 322 patients received lamivudine loo mg daily and 107patients received placebo treatment for 12 weeks. Then, all patients were offered a further 40 weeks ofopen 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 HBVDNA<1.6ng/L) rate in lamivudine group was higher than in placebo group (92.2% VS 14.1%, P<0.01), butat 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 gToup was higher than in placebo/lamivudinegroup (24.4% VS 8.5%, P<0.01). Proportion of HBeAg/anti-HBe serioconversion had no difference in twogroups (7.5% VS 5.2%, P>0.05). By week 12, ALT normalization rate in lamivudine group was higherthan in placebo gToup (60.3% VS 27.5%, P<0.01), but after 52 weeks treatment, there was no differencebetween two gToups (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 adverseevents was similar for both lamivudine and placebo/lamivudine group up to week 12 and 52. There wasfew severe drug-related adverse event. Conclusion Sustained HBV replication suppression could be obtainedfrom long-term treatment with lamivudine froing dally accompanied with good tolerance and safety.
出处
《中华肝脏病杂志》
CAS
CSCD
1999年第2期80-83,共4页
Chinese Journal of Hepatology
