Khorsi H, Castelain S, Wyseur A, Izopet J, Canva V, Rombout A, Capron D, Capron J P, Lunel F, Stuyver L, Duverlie G
Laboratoire de Virologie, Centre Hospitalo-Universitaire d'Amiens, France.
J Hepatol. 1997 Jul;27(1):72-7. doi: 10.1016/s0168-8278(97)80282-6.
BACKGROUND/AIMS: Studies of HCV quasispecies during interferon treatment have shown the selection of resistant clones. Enomoto et al. have defined the interferon sensitivity-determining region in an amino acid stretch of the HCV-1b NS5A region. Patients with a mutant strain before treatment were complete responders, whereas those with wild-type HCV-J strain were resistant to interferon. The same region was studied in HCV isolates of French patients.
Forty-three HCV-1b chronically infected patients, consisting of 26 non-responders and 17 complete responders to interferon-alfa treatment (3 MUI tiw for 6 months), were included retrospectively. We directly sequenced the NS5A(2209-2248) HCV region of these patients before treatment. The viral load could be obtained from six complete responders and 15 non-responders.
We detected wild-type and intermediate strains, but only two mutant strains were present. One of them was found in a non-responder. In three complete responders, we found a wild-type strain. The distribution of the various strains was rather different from that found in Japan. Before treatment, the viral load was lower in complete responders (p=0.01).
Only two mutant strains were detected in our study. This could partially explain the low response rate to interferon treatment of French HCV-1b-infected patients, although the dose regimen was lower than in Japanese studies. Also, wild-type strains were found in some complete responders, and no correlation was determined between the mutation number in the NS5A(2209-2248) region and response to alfa interferon therapy. This may be related to epidemiological differences between HCV-1b strains present in France and those in Japan. Searching for the mutant NS5A pattern before treatment does not appear to be useful in French patients as it is too uncommon.
背景/目的：对丙肝病毒（HCV）准种在干扰素治疗期间的研究显示会选择出耐药克隆。榎本等人已在HCV-1b NS5A区域的一段氨基酸序列中确定了干扰素敏感性决定区。治疗前携带突变株的患者是完全应答者，而携带野生型HCV-J株的患者对干扰素耐药。对法国患者的HCV分离株研究了同一区域。
回顾性纳入了43例HCV-1b慢性感染患者，其中26例对干扰素-α治疗（3百万国际单位，每周3次，共6个月）无应答，17例为完全应答者。我们在这些患者治疗前直接对NS5A（2209 - 2248）HCV区域进行了测序。病毒载量可从6例完全应答者和15例无应答者中获得。
我们检测到野生型和中间型毒株，但仅存在两个突变株。其中一个在无应答者中发现。在3例完全应答者中，我们发现了野生型毒株。各种毒株的分布与在日本发现的情况有很大不同。治疗前，完全应答者的病毒载量较低（p = 0.01）。
在我们的研究中仅检测到两个突变株。这可能部分解释了法国HCV-1b感染患者对干扰素治疗的低应答率，尽管剂量方案低于日本的研究。此外，在一些完全应答者中发现了野生型毒株，并且在NS5A（2209 - 2248）区域的突变数量与对α干扰素治疗的应答之间未确定相关性。这可能与法国和日本存在的HCV-1b毒株的流行病学差异有关。在法国患者中，治疗前寻找突变的NS5A模式似乎无用，因为其太不常见。
