The efficacy and safety of thymosin alpha-1 in Japanese patients with chronic hepatitis B; results from a randomized clinical trial
The efficacy and safety of thymosin alpha-1 in Japanese patients with chronic hepatitis B; results from a randomized clinical trial
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DOI：
10.1111/j.1365-2893.2005.00633.x
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发表时间：
2005-05-01
影响因子：
2.5
通讯作者：
Martins, EB
中科院分区：
文献类型：
--
作者：
Iino, S;Toyota, J;Martins, EB
胸腺法新（胸腺素α-1; T α 1）是一种28个氨基酸的多肽，其在治疗慢性肝炎B病毒（HBV）感染中显示出功效。本研究的目的是评价Ta 1治疗HBV-DNA阳性和丙氨酸氨基转移酶（ALT）水平异常高的慢性B型肝炎患者的长期、剂量相关疗效和安全性。共有316例患者随机接受0.8或1.6 mg T α 1单药治疗24周。在72周观察期结束时（停止治疗后12个月），1.6 mg治疗组中36.4%的患者实现ALT正常化，30%通过分支DNA实现HBV-DNA清除，15%通过转录介导的扩增实现HBV-DNA清除，22.8%实现HBeAg-抗原清除。0.8 mg治疗组患者的疗效率相似，尽管晚期纤维化患者接受1.6 mg Ta 1单药治疗时的缓解率显著优于0.8 mg（通过组内分析确定;患者未通过肝活检分层）。所有药物不良反应均为轻度，多涉及肝酶波动，最可能与对Ta 1治疗的应答引起的积极免疫效应有关。1.6 mg和0.8 mg治疗组的不良事件发生率相似。总之，0.8和1.6 mg剂量的Ta 1对B型肝炎具有长期疗效，安全性特征良好。
Thymalfasin ( thymosin alpha-1; T alpha 1) is a 28-amino acid polypeptide that has shown efficacy in the treatment of chronic hepatitis B virus (HBV) infection. The objective of this study was to evaluate the long-term, doserelated efficacy and safety of Ta1 treatment in chronic hepatitis B patients with positive HBV-DNA and abnormally high alanine aminotransferase (ALT) levels. A total of 316 patients were randomized to receive either 0.8 or 1.6 mg of T alpha 1 monotherapy for 24 weeks. At the end of the 72- week observation period ( 12 months after cessation of therapy), 36.4% of patients in the 1.6- mg treatment group achieved normalization of ALT, 30% achieved clearance of HBV-DNA by branched DNA vs 15% by transcription-mediated amplification, and 22.8% achieved clearance of HBe-antigen. Patients in the 0.8-mg treatment group achieved similar efficacy rates, although patients with advanced fibrosis demonstrated a significantly better response rate when treated with 1.6 mg of Ta1 monotherapy vs 0.8 mg ( as determined by intragroup analysis; patients were not stratified by liver biopsy). All adverse drug reactions were mild and most involved the fluctuation of liver enzymes, which was most likely related to the positive immune effects caused by the response to Ta1 treatment. Adverse event incidence was similar in the 1.6- and 0.8- mg treatment groups. In conclusion, Ta1 at doses of 0.8 and 1.6 mg exhibits long-term efficacy against hepatitis B with a good safety profile.