Squadrito G, Leone F, Sartori M, Nalpas B, Berthelot P, Raimondo G, Pol S, Bréchot C
INSERM Unité 370, Centre hospitalo-universitaire Necker, Paris, France.
Gastroenterology. 1997 Aug;113(2):567-72. doi: 10.1053/gast.1997.v113.pm9247477.
BACKGROUND & AIMS: Mutations in hepatitis C virus (HCV) nonstructural protein 5A (NS5A) may correlate with response to interferon in Japanese patients with chronic hepatitis C. The aim of this study was to examine whether these findings could be expanded to European patients infected with genotypes associated to low (1b) or high (3a) response rates.
Pretreatment serum samples of 66 patients with chronic HCV infection, 48 infected with genotype 1b and 18 with 3a, were analyzed.
Among patients infected with genotype 3a, 1 of 7 long-term responders and none of 11 nonresponders showed NS5A amino acid mutations. Among patients infected with genotype 1b, all 7 long-term responders, but also 27 of 41 nonresponders, showed NS5A mutations. There was no correlation between number of mutations and response to therapy. In 10 patients, sequences obtained before and after treatment were compared and failed to show any change. Serum HCV RNA levels did not differ between patients with and without mutations in NS5A sequence.
No significant correlation was found in patients infected with genotypes 1b or 3a between NS5A sequence and response to interferon alfa. NS5A mutations do not correlate with viral load. Changes in this region were not found during interferon alfa treatment.
在日本慢性丙型肝炎患者中，丙型肝炎病毒（HCV）非结构蛋白5A（NS5A）的突变可能与对干扰素的反应相关。本研究旨在探讨这些发现是否能扩展至感染低反应率（1b型）或高反应率（3a型）相关基因型的欧洲患者。
分析了66例慢性HCV感染患者的治疗前血清样本，其中48例感染1b型，18例感染3a型。
在感染3a型的患者中，7例长期应答者中有1例、11例无应答者中无1例出现NS5A氨基酸突变。在感染1b型的患者中，所有7例长期应答者以及41例无应答者中的27例均出现NS5A突变。突变数量与治疗反应之间无相关性。对10例患者治疗前后获得的序列进行比较，未发现任何变化。NS5A序列有突变和无突变的患者之间血清HCV RNA水平无差异。
在感染1b型或3a型的患者中，未发现NS5A序列与对α干扰素的反应之间存在显著相关性。NS5A突变与病毒载量无关。在α干扰素治疗期间未发现该区域有变化。
