基因型、干扰素治疗期间病毒滴度缓慢下降以及高变区的高度序列变异性表明丙型慢性肝炎患者对干扰素治疗反应不佳。

Genotype, slow decrease in virus titer during interferon treatment and high degree of sequence variability of hypervariable region are indicative of poor response to interferon treatment in patients with chronic hepatitis type C.

作者信息

Chayama K, Tsubota A, Arase Y, Saitoh S, Ikeda K, Matsumoto T, Hashimoto M, Kobayashi M, Kanda M, Morinaga T

机构信息

Department of Gastroenterology, Toranomon Hospital, Okinaka Memorial Institute for Medical Study, Tokyo, Japan.

出版信息

J Hepatol. 1995 Dec;23(6):648-53. doi: 10.1016/0168-8278(95)80029-8.

DOI:10.1016/0168-8278(95)80029-8

PMID:8750162

Abstract

In a study assessing factors associated with a good or a poor response to interferon treatment in patients with chronic hepatitis type C, we analyzed serum samples taken from 26 interferon-treated patients and found further evidence that infection with genotype II is associated with a poor response. Whereas all seven patients with group III genotype tested showed a good response (normalization of alanine aminotransferase level for more than 6 months), only 10 of 19 (53%) patients infected with group II genotype showed a good response. We also observed that 16 of 17 (94%) patients who exhibited a rapid virus titer decrease during the first 2 weeks of treatment later showed a good response. In contrast, only three of nine (33%) patients with an initially slow viral decrease eventually showed a good response (p<0.04). None of the 26 control patients exhibited a marked virus decrease or normalization of serum alanine aminotransferase level. Interestingly, high degrees of sequence variability were seen in three patients with group II hepatitis C virus who responded poorly to the therapy. All three showed slow decreases in virus titer during the first 2 weeks of treatment. In contrast, patients with genotype II who showed a good response to treatment were seen to have very few mutations. In three patients with genotype III who had responded well to interferon treatment, all showed very little amino acid sequence variability in the hypervariable region compared with patients with genotype II who had responded poorly to interferon treatment. These data suggest that a slow decrease in virus titer during the beginning of interferon treatment and a high degree of sequence variability, both of which are often seen in patients with group II genotype, are associated with poor response to interferon treatment.

摘要

在一项评估慢性丙型肝炎患者对干扰素治疗反应良好或不佳相关因素的研究中，我们分析了26例接受干扰素治疗患者的血清样本，发现了进一步的证据表明II型基因型感染与反应不佳有关。所有7例检测为III型基因型的患者均显示出良好反应（丙氨酸转氨酶水平正常化超过6个月），而19例感染II型基因型的患者中只有10例（53%）显示出良好反应。我们还观察到，在治疗的前2周内病毒滴度迅速下降的17例患者中有16例（94%）后来显示出良好反应。相比之下，最初病毒下降缓慢的9例患者中只有3例（33%）最终显示出良好反应（p<0.04）。26例对照患者中无一例出现明显的病毒下降或血清丙氨酸转氨酶水平正常化。有趣的是，3例对治疗反应不佳的II型丙型肝炎病毒患者出现了高度的序列变异性。这3例患者在治疗的前2周内病毒滴度均缓慢下降。相比之下，对治疗反应良好的II型基因型患者的突变很少。在3例对干扰素治疗反应良好的III型基因型患者中，与对干扰素治疗反应不佳的II型基因型患者相比，其高变区的氨基酸序列变异性均很小。这些数据表明，干扰素治疗开始时病毒滴度缓慢下降和高度的序列变异性，这两者在II型基因型患者中经常出现，与干扰素治疗反应不佳有关。