通过单链构象多态性检测丙型肝炎病毒复杂性及对干扰素治疗的反应

Hepatitis C viral complexity detected by single-strand conformation polymorphism and response to interferon therapy.

作者信息

Moribe T, Hayashi N, Kanazawa Y, Mita E, Fusamoto H, Negi M, Kaneshige T, Igimi H, Kamada T, Uchida K

机构信息

Diagnostic Science Department, Shionogi Biomedical Laboratories, Shionogi & Co., Ltd., Osaka, Japan.

出版信息

Gastroenterology. 1995 Mar;108(3):789-95. doi: 10.1016/0016-5085(95)90452-2.

DOI:10.1016/0016-5085(95)90452-2

PMID:7533113

Abstract

BACKGROUND/AIMS: Hepatitis C virus (HCV) genome heterogeneity by sequence analysis in association with interferon (IFN) inefficacy has been reported. This study was performed to establish a convenient method for detecting the HCV quasispecies complexity and to determine the correlation between the complexity and the responsiveness to IFN therapy in patients with chronic hepatitis C.

METHODS

The quasispecies complexity of HCV hypervariable region 1 in patients treated with IFN-alpha was analyzed by polymerase chain reaction-mediated single-strand conformation polymorphism (SSCP).

RESULTS

Seven of 25 patients (28%) with low complexity (SSCP band number of < or = 2) were HCV RNA negative after treatment, whereas in 24 patients with high complexity (SSCP band number of > or = 3), the response to IFN was almost insignificant because only 1 patient (4.5%) remained HCV RNA negative after treatment (P < 0.05). Among type 1b patients, IFN therapy was only effective for patients with low amounts of HCV RNA (< or = 10(7.5) copies/mL serum) and low complexity. In contrast, most type 2a patients tended to respond to the therapy with exceptions being those with high amounts of HCV RNA and high complexity.

CONCLUSIONS

The complexity of the hypervariable region 1 quasispecies may be a factor for predicting IFN inefficacy in patients with chronic hepatitis C.

摘要

背景/目的：已有报道称，通过序列分析发现丙型肝炎病毒（HCV）基因组异质性与干扰素（IFN）治疗无效有关。本研究旨在建立一种便捷的方法来检测HCV准种复杂性，并确定慢性丙型肝炎患者中该复杂性与IFN治疗反应性之间的相关性。

方法

采用聚合酶链反应介导的单链构象多态性（SSCP）分析接受α-干扰素治疗患者的HCV高变区1准种复杂性。

结果

25例复杂性低（SSCP条带数≤2）的患者中，7例（28%）治疗后HCV RNA呈阴性；而在24例复杂性高（SSCP条带数≥3）的患者中，IFN治疗反应几乎不明显，因为治疗后仅1例患者（4.5%）HCV RNA仍为阴性（P<0.05）。在1b型患者中，IFN治疗仅对HCV RNA量低（≤10⁷.⁵拷贝/毫升血清）且复杂性低的患者有效。相比之下，大多数2a型患者倾向于对治疗有反应，但HCV RNA量高且复杂性高的患者除外。