All-trans retinoic acid for treatment of chronic hepatitis C
All-trans retinoic acid for treatment of chronic hepatitis C
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DOI：
10.1111/j.1478-3231.2007.01666.x
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发表时间：
2008-03-01
影响因子：
6.7
通讯作者：
Galle, Peter R.
中科院分区：
文献类型：
--
作者：
Boecher, Wulf O.;Wallasch, Christian;Galle, Peter R.
背景/目的：丙型肝炎病毒亚基因组复制子系统的体外研究已经证实全反式维甲酸(ATRA)是一种潜在的治疗丙型肝炎的药物。因此，应该在体内评估该药物的抗病毒潜力。方法：20例对常规或聚乙二醇化干扰素-α(Peg-/干扰素-α)和利巴韦林无反应的高度治疗的1型患者随机分为两组，A组单用ATRA(A组)，B组单用ATRA(ATRA+PEGIFN-α2a)治疗12周。用BDNA法检测HCVRNA，如果阴性，用高灵敏的聚合酶链式反应检测。结果：治疗8周后，A组10例中5例病毒血症下降，B组10例中5例病毒血症2log下降，3例血清丙型肝炎病毒核糖核酸清除。停药后病毒血症复发。全反式维甲酸耐受性相当好，以一过性头痛、皮肤干燥和粘膜为最常见的副作用。结论：ATRA单一疗法的病毒载量减少，虽然有限且短暂，但支持ATRA的抗病毒活性。然而，在接受全反式维甲酸和聚乙二醇化干扰素-2a治疗的10名先前无应答者中，有3名患者的丙型肝炎病毒RNA迅速丧失，这表明了一种强大的相加或协同的全反式维甲酸效应，需要进行一项对照试验来评估这种药物的治疗潜力。
Background/Aims: In vitro studies in the subgenomic hepatitis C virus (HCV) replicon system have identified all-trans retinoic acid (ATRA) as a potential therapeutic against hepatitis C. Thus, the antiviral potential of this drug should be assessed in vivo. Methods: Twenty highly treatment experienced serotype 1 patients with non-response to conventional or pegylated interferon-alpha (Peg-/IFN-alpha) and ribavirin were randomly assigned to 12 weeks of monotherapy with ATRA (group A) or a combination of ATRA and PegIFN-alpha 2a ( group B). HCV RNA was assessed by bDNA assay and if negative by highly sensitive polymerase chain reaction. Results: During treatment, five of 10 patients in group A had a drop of viraemia > 1log, while in group B after 8 weeks five of 10 dropped > 2log, and three of 10 cleared HCV RNA from serum. Viraemia relapsed after treatment cessation. ATRA was rather well tolerated, with transient headache, dry skin and mucosa representing the most common side effects. Conclusions: The viral load reduction under ATRA monotherapy, although limited and transient, supports the antiviral activity of ATRA. However, the rapid loss of HCV RNA in three of 10 previous non-responders under ATRA and PegIFN-alpha 2a treatment demonstrates a strong additive or synergistic ATRA effect and calls for a controlled trial to assess the therapeutic potential of this drug.