Long-term efficacy and safety of adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B
Long-term efficacy and safety of adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B
复制标题
DOI：
10.1002/hep.22414
复制
发表时间：
2008-09-01
期刊：
影响因子：
13.5
通讯作者：
Rousseau, Franck
中科院分区：
文献类型：
--
作者：
Marcellin, Patrick;Chang, Ting-Tsung;Rousseau, Franck
171例B e抗原（HBeAg）阳性的慢性B型肝炎（CH B）患者接受阿德福韦酯（ADV）10 mg治疗48周后，与安慰剂相比，组织学、病毒学、血清学和生化学均有显著改善。ADV在这些患者中的一个亚组中的长期疗效和安全性研究长达5年。第1年接受ADV 10 mg治疗的65例患者选择继续参加长期安全性和疗效研究（LTSES）。入组时，65例USES患者的中位年龄为34岁，83%为男性，74%为亚洲人，23%为高加索人，中位基线血清B病毒（HBV）DNA为8.45 log（10）拷贝/mL，中位基线丙氨酸氨基转移酶（ALT）为2.0 X正常值上限。研究5年时，仍在接受ADV治疗的41例患者血清HBV DNA和ALT较基线的中位变化分别为4.05 log（10）拷贝/mL和-50 U/L。在研究结束时，分别有58%和48%的患者观察到HBeAg丢失和血清转换。15例患者进行了基线和随访结束时的肝活检;分别在67%和60%的患者中观察到坏死性炎症和纤维化的改善。阿德福韦酯耐药突变A18 IV或N236 T在13例USES患者中发展;第一次观察是在研究第195周。有没有严重的不良事件有关ADV。结论：ADV治疗超过48周耐受性良好，并产生长期的病毒学，生化，血清学和组织学的改善。
Treatment of 171 patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) with adefovir dipivoxil (ADV) 10 mg over 48 weeks resulted in significant histological, virological, serological, and biochemical improvement compared with placebo. The long-term efficacy and safety of ADV in a subset of these patients was investigated for up to 5 years. Sixty-five patients given ADV 10 mg in year 1 elected to continue in a long-term safety and efficacy study (LTSES). At enrollment, the 65 USES patients were a median 34 years old, 83% male, 74% Asian, 23% Caucasian, median baseline serum hepatitis B virus (HBV) DNA 8.45 log(10) copies/mL, and median baseline alanine aminotransferase (ALT) 2.0 X upper limit of normal. At 5 years on study, the median changes from baseline in serum HBV DNA and ALT for the 41 patients still on ADV were 4.05 log(10) copies/mL and -50 U/L, respectively. HBeAg loss and seroconversion were observed in 58% and 48% of patients by end of study, respectively. Fifteen patients had baseline and end of follow-up liver biopsies; improvements in necroinflammation and fibrosis were seen in 67% and 60% of these patients, respectively. Adefovir resistance mutations A18IV or N236T developed in 13 USES patients; the first observation was at study week 195. There were no serious adverse events related to ADV. Conclusion: Treatment with ADV beyond 48 weeks was well tolerated and produced long-term virological, biochemical, serological, and histological improvement.