拉米夫定治疗慢性乙型肝炎和重症肝病

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文题：Lamivudine for Patients with Chronic Hepatitis B and Advanced Liver Disease
作者：Yun-Fan Liaw, M.D., Joseph J.Y. Sung, M.D., Wan Cheng Chow, M.D., Geoffrey Farrell, M.D., Cha-Ze Lee, M.D., Hon Yuen, M.D., Tawesak Tanwandee, M.D., Qi-Min Tao, M.D., Kelly Shue, M.R.Pharm.S., Oliver N. Keene, M.Sc., Jonathan S. Dixon, Ph.D., D. Fraser Gray, Ph.D., and Jan Sabbat, M.B., B.S., for the Cirrhosis Asian Lamivudine Multicentre Study Group
杂志全名： The new england journal of medicine
年份，卷（期）: 起止页码： 2004;351:1521-31.
英文摘要：
Background
The effectiveness of antiviral therapy in preventing disease progression in patients with chronic hepatitis B and advanced fibrosis or cirrhosis is unknown.
Methods
Patients with chronic hepatitis B who had histologically confirmed cirrhosis or advanced fibrosis were randomly assigned in a 2:1 ratio to receive lamivudine (100 mg per day) or placebo for a maximum of five years. Of 651 patients, 436 were assigned to receive lamivudine and 215 to receive placebo. The primary end point was time to disease progression, defined by hepatic decompensation, hepatocellular carcinoma, spontaneous bacterial peritonitis, bleeding gastroesophageal varices, or death related to liver disease.An independent data and safety monitoring board monitored the progress of the study and performed interim analyses of the data.
Results
We randomly assigned 651 patients (98 percent Asian and 85 percent male) to receive lamivudine or placebo. The study was terminated after a median duration of treatment of 32.4 months (range, 0 to 42) owing to a significant difference between treatment groups in the number of end points reached. End points were reached by 7.8 percent of the patients receiving lamivudine and 17.7 percent of those receiving placebo (hazard ratio for disease progression, 0.45; P=0.001). The Child–Pugh score increased in 3.4 percent of the patients receiving lamivudine and 8.8 percent of those receiving placebo (hazard ratio, 0.45; P=0.02), whereas hepatocellular carcinoma occurred in 3.9 percent of those in the lamivudine group and 7.4 percent of those in the placebo group (hazard ratio, 0.49; P=0.047). Genotypic resistance YMDD mutations developed in 49 percent of the patients treated with lamivudine, and the Child–Pugh score was more likely to increase in patients with these mutations than in the other patients treated with lamivudine (7 percent vs. <1 percent). Overall, 12 percent of the patients in the lamivudinegroup and 18 percent of the patients in the placebo group reported serious adverse events.
Conclusions
Continuous treatment with lamivudine delays clinical progression in patients with chronic hepatitis B and advanced fibrosis or cirrhosis by significantly reducing the incidence of hepatic decompensation and the risk of hepatocellular carcinoma.
中文译文：
拉米夫定治疗慢性乙型肝炎和重症肝病
[摘要]
背景；
抗病毒治疗在预防乙型肝炎和严重纤维化或肝硬化的患者病情发展方面的有效性尚不为人所知。
方法；
经组织学检查确定有肝硬化或严重纤维化的乙型肝炎患者，按2：1的比例随机进行分组，分别给予拉米夫定(100 mg每天)或安慰剂，最长观察期为5年。651例患者中，436例接受拉米夫定，215例应用安慰剂。主要终点事件是疾病进展（定义为肝脏失代偿，肝细胞癌，自发性细菌性腹膜炎，静脉曲张引起的上消化道出血或与肝病相关的死亡）的时间。独立的数据和安全监控委员会对研究过程进行监控并对数据资料进行分析。
结果；
651例患者(98 %为亚洲人，85%为男性)被随机安排接受拉米夫定或安慰剂治疗。当治疗时程的中位数达到32.4个月（范围为0到42个月）时，因为两组之间在达到研究终点的数量上出现显著差异终止研究。拉米夫定组7.8%的患者，安慰剂组17.7%的患者达到研究终点（疾病加重的危险率为0.45，P=0.001）。接受拉米夫定的患者中，3.4%的Child–Pugh积分升高，而安慰剂组中8.8%的人升高（危险率0.45; P=0.02），而拉米夫定组3.9%的患者，安慰剂组7.4%的患者发生肝细胞癌(危险率0.49; P=0.047)。接受拉米夫定治疗者中49%出现基因型抗YMDD突变，且Child–Pugh积分在这些发生突变的患者中比未发生突变的拉米夫定组患者要高（7%vs<1%）。总体而言，拉米夫定组中12%的患者，安慰剂组中18%的患者报道有严重不良事件发生。
结论；
对于乙型肝炎和严重纤维化或肝硬化的患者，连续应用拉米夫定治疗使肝脏失代偿和肝细胞癌的发生率显著降低，从而延缓疾病的临床进展，

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