|
 
- 现金
- 13255 元
- 精华
- 9
- 帖子
- 7621
- 注册时间
- 2003-11-5
- 最后登录
- 2012-12-19
|
1楼
发表于 2008-1-29 19:43
目前，已有研究证实了慢性乙肝患儿短期接受拉米夫定的安全性和有效性，但是最佳疗程和长期治疗安全性问题尚未明确。美国Jonas等学者的一项研究显示，在慢性乙肝患儿接受拉米夫定治疗的3年中，抗病毒疗效及安全性均可。
这项前瞻性研究从9个国家的医学中心纳入151例慢性乙肝患儿，收集其体重、身高、症状、体征等基本病历资料，以及转氨酶水平、血清学病毒标志物、乙肝病毒（HBV）DNA水平以及严重不良事件（SAE）等。在研究开始第1年中，患儿随机接受拉米夫定或安慰剂治疗。在随后的2年中，HBeAg仍为阳性的患儿继续接受拉米夫定治疗，而HBeAg转阴的患儿接受随访。研究将病原学应答定义为研究至第3年末时，患者HBeAg转阴且血清中HBV-DNA检测不到。
结果显示，拉米夫定治疗1年和至少2年的患儿，持续HBeAg血清转换率分别为82%和>90%，安慰剂治疗后的血清转换率为75%。8例HBsAg转阴患儿均接受了拉米夫定治疗。
在研究期间，受试者均未出现与拉米夫定相关的SAE，治疗亦未影响患儿的体重、身高等发育。2%患儿发生丙氨酸氨基转移酶（ALT）突然升高，并大于正常值的10倍，接受拉米夫定治疗者可获得较好预后。
J Viral Hepat. 2008 Jan;15(1):20-27.
Long-term lamivudine treatment of children with chronic hepatitis B: durability of therapeutic responses and safety.
Jonas MM, Little NR, Gardner SD; Members of the International Pediatric Lamivudine Investigator Group.
Division of Gastroenterology, Children’s Hospital Boston, Boston, MA, USA.
Lamivudine has been demonstrated safe and efficacious in the short term in a large cohort of children with chronic hepatitis B (CHB), but optimal duration of treatment has not been elucidated and limited data on the safety of long-term lamivudine administration have been reported. In addition, the durability of favourable therapeutic outcomes after lamivudine therapy in children has not been well characterized. The aim of this study was to examine the safety of lamivudine and the durability of clinical responses in a group of children who received up to 3 years of treatment for CHB. One hundred and fifty-one children from centres in nine countries who had previously received lamivudine in a large prospective trial were enrolled. During the first year, children had been randomized to either lamivudine or placebo treatment. Subsequently, in a separate extension study, those who remained hepatitis B e antigen (HBeAg) positive were given lamivudine for up to 2 years and those who were HBeAg negative were observed for additional 2 years. Results of these studies have been previously reported. In this study, these children were followed for 2 additional years. Data gathered from medical record review included weight, height, signs and symptoms of hepatitis, alanine aminotransferase (ALT) levels, serologic markers, hepatitis B virus (HBV) DNA levels and serious adverse events (SAEs). Other pharmacological treatments for CHB were allowed according to the practices of individual investigators and were documented. Subjects were divided into two groups for analysis, those who had achieved virological response (VR), defined as HBeAg negative and undetectable HBV DNA by the bDNA assay by the end of the extension study at 3 years, and those who had not. In those who had achieved VR by the end of the extension study, long-term durability of HBeAg seroconversion was 82% and >90% in those who had received lamivudine for 52 weeks and at least 2 years respectively. This compares to 75% for those who had achieved seroconversion after placebo. In those who had not achieved VR by the end of the extension study, an additional 11% did so by the end of the study; they had all received lamivudine in the previous trial, and none had received further treatment during the study. Eight children lost hepatitis B surface antigen during the study and all had received lamivudine at some point during the previous trials. Evaluation of safety data revealed no SAEs related to lamivudine. There was no effect of treatment on weight or height z scores. Clinically benign ALT flares (>10 times normal) were seen in 2% of children. Favourable outcomes from lamivudine treatment of CHB in children are maintained for at least several years after completion of treatment. Up to 3 years of lamivudine treatment is safe in children. |
|
