Twenty-four-week clevudine therapy showed potent and sustained antiviral activity in HBeAg-positive chronic hepatitis B
Twenty-four-week clevudine therapy showed potent and sustained antiviral activity in HBeAg-positive chronic hepatitis B
复制标题
DOI：
10.1002/hep.21629
复制
发表时间：
2007-05-01
期刊：
影响因子：
13.5
通讯作者：
Lee, Hyo-Suk
中科院分区：
文献类型：
--
作者：
Yoo, Byung Chul;Kim, Ju Hyun;Lee, Hyo-Suk
氯夫定是一种嘧啶类似物，对HBV具有有效和持续的抗病毒活性。本研究评估了每日一次30mg氯夫定24周的安全性和有效性，并评估了停药后24周的持久抗病毒反应。共有243例乙型肝炎e抗原（HBeAg）阳性的慢性乙型肝炎患者随机（3:1）接受克拉夫定30 mg每日一次（n = 182）或安慰剂（n = 61），为期24周。患者接受了24周的后续治疗。在第24周时，克利夫定组和安慰剂组的中位血清HBV DNA较基线减少量分别为5.10和0.27 log（10）拷贝/mL （P < 0.0001）。克利夫定组的病毒抑制持续治疗，第34周降低3.73 log(10)，第48周降低2.02 log（10）。在第24周，59.0%的clevudine组患者的血清HBV DNA水平无法通过Amplicor PCR检测（低于300拷贝/mL）。在第24周，丙氨酸转氨酶（ALT）水平达到正常化的患者比例，克利夫定组为68.2%，安慰剂组为17.5% （P < 0.0001）。在治疗后随访期间，克夫定组ALT恢复正常。克利夫定组和安慰剂组的不良事件发生率相似。用药24周时，未见对氯夫定耐药。结论：克利夫定治疗hbeag阳性慢性乙型肝炎24周耐受性良好，抗病毒效果持续有效，治疗期间无病毒耐药迹象。
Clevudine is a pyrimidine analogue with Potent and sustained antiviral activity against HBV. The present study evaluated the safety and efficacy of 30 mg clevudine once daily for 24 weeks and assessed the durable antiviral response for 24 weeks after cessation of dosing. A total of 243 hepatitis B e antigen (HBeAg) -positive chronic hepatitis B patients were randomized (3:1) to receive clevudine 30 mg once daily (n = 182) or placebo (n = 61) for 24 weeks. Patients were followed for a further 24 weeks off therapy. Median serum HBV DNA reductions from baseline at week 24 were 5.10 and 0.27 log(10) copies/mL in the clevudine and placebo groups, respectively (P < 0.0001). Viral suppression in the clevudine group was sustained off therapy, with 3.73 log(10) reduction at week 34 and 2.02 log(10) reduction at week 48. At week 24, 59.0% of patients in the clevudine group had undetectable serum HBV DNA levels by Amplicor PCR assay (less than 300 copies/mL). The proportion of patients who achieved normalization of alanine aminotransferase (ALT) levels was 68.2% in the clevudine group and 17.5% in the placebo group at week 24 (P < 0.0001). ALT normalization in the clevudine group was well maintained during post-treatment follow-up period. The incidence of adverse events (AEs) was similar between the clevudine group and the placebo group. No resistance to clevudine was detected with 24 weeks of administration of drug. Conclusion: A 24-week clevudine therapy was well tolerated and showed potent and sustained antiviral effect without evidence of viral resistance during treatment period in HBeAg-positive chronic hepatitis B.