A pilot study of therapeutic vaccination with envelope protein E1 in 35 patients with chronic hepatitis C
A pilot study of therapeutic vaccination with envelope protein E1 in 35 patients with chronic hepatitis C
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DOI：
10.1053/jhep.2003.50474
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发表时间：
2003-11-01
期刊：
影响因子：
13.5
通讯作者：
Hulstaert, F
中科院分区：
文献类型：
--
作者：
Nevens, F;Roskams, T;Hulstaert, F
对于无法清除病毒的慢性丙型肝炎患者，需要新的治疗方法。35例慢性丙型肝炎患者（基因型1）随机接受20 μ g重组HCV E1（E1）（n = 26）或安慰剂（n = 9）在第0，4，8，12和24周肌肉注射。34名受试者在第50、53、56、59、62和65周接受开放标签E1疫苗。24例患者（12例男性，12例女性;平均年龄52岁; 18例干扰素治疗失败;平均基线丙氨酸氨基转移酶[ALT]水平为118 IU/L）在2个疗程E1治疗前后（17个月后）进行了活检。由2名盲态病理学家根据Ishak和Metavir系统对肝脏组织学进行评分。注射后反应与安慰剂相似（仅明矾）。24例患者中有9例（38%）的总Ishak评分改善2分或以上，10例（41%）保持稳定，5例（21%）显示恶化。9名患者（38%）的Ishak和Metavir纤维化评分均有所改善。血浆HCV-RNA水平保持不变，而ALT水平在治疗期间呈下降趋势。除3例患者外，所有患者均发生了显著的从头E1特异性T细胞应答。抗E1抗体水平的升高与总Ishak评分的降低以及Ishak纤维化评分和ALT水平的相对降低相关（均P <0.01）。总之，E1治疗性疫苗接种耐受性良好，观察到的效果值得进一步研究。
New treatments are needed for chronic hepatitis C patients in whom viral clearance cannot be achieved. Thirty-five chronic hepatitis C patients (genotype 1) were randomized to receive 20 jig of recombinant HCV E1 (E1) (n = 26) or placebo (n = 9) intramuscularly at weeks 0, 4, 8, 12, and 24. Thirty-four then received open-label E1 vaccine at weeks 50, 53, 56, 59, 62, and 65. Twenty-four patients (12 men, 12 women; mean age, 52 y; 18 interferon-based treatment failures; mean baseline alanine aminotransferase [ALT] level, 118 IU/L) underwent a biopsy before and after 2 courses of E1, 17 months later. Liver histology was scored by 2 blinded pathologists according to the Ishak and Metavir systems. Postinjection reactions were similar to placebo (alum only). Nine of 24 patients (38%) had improvement of 2 points or more, 10 (41%) remained stable, and 5 (21%) showed worsening in total Ishak score. Nine patients (38%) improved both on Ishak and Metavir fibrosis scores. Plasma HCV-RNA levels remained unchanged, whereas ALT levels showed a trend toward a decrease during treatment. All but 3 patients developed a significant de novo E1-specific T-cell response. The increase in anti-E1 antibody levels correlated with the decrease in total Ishak score and with the relative decreases in both Ishak fibrosis score and ALT level (all Pless than or equal to.01). In conclusion, E1 therapeutic vaccination is well tolerated and the observed effects warrant further study.