Nagasaka A, Hige S, Tsunematsu I, Yoshida J, Sasaki Y, Matsushima T, Asaka M
Third Department of Internal Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
J Med Virol. 1996 Nov;50(3):214-20. doi: 10.1002/(SICI)1096-9071(199611)50:3<214::AID-JMV2>3.0.CO;2-C.
Some chronic hepatitis C patients show sustained response to interferon (IFN) therapy despite viremia. This condition seems to be related to the density populations of hepatitis C virus (HCV) [Kanto et al. (1995): J Med Virol 46:230-237]. To investigate further the relationship between alanine aminotransferase (ALT) levels after IFN therapy and the HCV density populations, we undertook differential flotation centrifugation of HCV and single strand conformation polymorphism targeted the hypervariable region (HVR) of E2 glycoprotein, which seems to be related to the density populations. Sera were obtained serially from 12 patients who had undergone IFN therapy (six sustained responders with viremia, six nonresponders). During the follow-up after interferon therapy, the HVR heterogeneities changed in 9 of the 12 patients. The remaining three patients whose heterogeneities did not changed persistently showed normal ALT. The changes in HVR heterogeneities were less pronounced in the sustained responders with viremia than in nonresponders; however, their density populations were prominently high in both responders. In two cases, changes in HVR heterogeneities and increase in low-density virion were observed before the hepatitis flare-up. These data indicate that HVR quasispecies show more relation to ALT levels after IFN therapy than HCV density populations and that the changes in the HVR sequences and HCV density populations may be associated with ALT elevation in some patients.
一些慢性丙型肝炎患者尽管存在病毒血症，但对干扰素（IFN）治疗仍表现出持续应答。这种情况似乎与丙型肝炎病毒（HCV）的密度群体有关[关户等人（1995年）：《医学病毒学杂志》46：230 - 237]。为了进一步研究IFN治疗后丙氨酸氨基转移酶（ALT）水平与HCV密度群体之间的关系，我们对HCV进行了差速浮选离心，并对似乎与密度群体有关的E2糖蛋白高变区（HVR）进行了单链构象多态性分析。从12例接受IFN治疗的患者（6例病毒血症持续应答者，6例无应答者）中连续采集血清。在干扰素治疗后的随访期间，12例患者中有9例的HVR异质性发生了变化。其余3例异质性未持续改变的患者ALT一直正常。病毒血症持续应答者的HVR异质性变化不如无应答者明显；然而，两者应答者的密度群体均显著较高。在2例患者中，在肝炎发作前观察到HVR异质性变化和低密度病毒粒子增加。这些数据表明，与HCV密度群体相比，HVR准种与IFN治疗后的ALT水平关系更密切，并且HVR序列和HCV密度群体的变化可能与某些患者的ALT升高有关。
