ANALYSIS OF HEPATITIS C VIRUS SUBTYPES AND ITS CLINICAL SIGNIFICANCE.

探讨丙型肝炎病毒（HCV）亚型的临床意义。采用特异性cDNA探针在NS5区印迹检测HCV的7个亚型（1a、1b、2a、2b、3a、3b、4a）。在从世界各地获得的约1600份样本中，未发现HCV-3b，偶尔检测到HCV-4a，主要在非洲的样本中。说明这两种类型仅在有限的地区分布，而其他5种类型普遍分布在世界各地。为了获得准确的HCV亚型结果，需要结合不同的分型方法进行综合分析。在日本的一项全国性分析中，证实干扰素（IFN）治疗HCV - 1b相关患者的效果明显优于非相关患者。在西方国家，干扰素治疗HCV-3a患者的效果往往优于HCV-1b患者。在IFN治疗期间，HCV滴度的变化模式分为快速下降(A)型、高滴型、更持续(C)型和介于A型和C型之间的中间(B)型。仅在HCV-1b患者中发现了C型的模式，而在HCV-2a和2b患者中没有发现，提示不同HCV亚型之间IFN效应的差异可能是由于HCV亚型质量的差异，而不是由于HCV- rna的数量。利用单链构象多态性分析了HCV在IFN敏感性决定区域的全种群。C型准种以ifn耐药型居多。另一方面，A型准种以IFN敏感型最多。HCV-1b在世界不同国家的患病率与肝细胞癌（HCC）的发病率显著相关。在日本，不同县的HCV-1b患病率与HCC死亡率之间存在显著相关性。HCC患者中HCV-1b的患病率明显高于非HCC患者。HCV-1b发生HCC的时间比其他HCV亚型短。这些结果提示HCV-1b的致癌性可能比其他HCV亚型更强。少

Clinical significance of the subtypes of hepatitis C virus (HCV) was studied. Seven (1a, 1b, 2a, 2b, 3a, 3b, 4a) subtypes of HCV were determined by blotting using type specific cDNA probes at the NS5 region. In about 1,600 samples obtained from the world, HCV-3b was not found, and HCV-4a was detected occasionally mainly in samples from Africa. indicating these two types distributed in only limited area, and the other 5 types commonly distributed through the world. To obtain the accurate results of HCV subtypes, a combined analysis with different methods for typing was needed. In a nationwide analysis in Japan, it was confirmed that the effects of interferon (IFN) treatment were significantly better in HCV 1b-related patients than in non-related patients. In the Western countries, the effect of IFN treatment tended to be better in patients with HCV-3a than HCV-1b. The pattern of changes in HCV titers during IFN treatment was classified into 3 types : rapid decreased (A) type, high titer … More sustained (C) type and intermediate (B) type between A and C types. The pattern of C type was found only in patients with HCV-1b and not with HCV-2a and-2b, suggesting that the difference of IFN effects between HCV subtypes may be attributed to the difference of quality of HCV subtypes and not to the quantities of HCV-RNA.Quansispesies population of HCV at the IFN sensitivity determining region were analyzed using single strand conformation polymorphism. In C type, the most quasispesies were IFN-resistance type. On the other hand, the most quasispesies in A type were IFN sensitive type. The prevalence of HCV-1b in different countries of the world was significantly correlated with the incidence of hepatocellular carcinoma (HCC). In Japan, a significant correlation between the prevalence of HCV-1b and mortality rate by HCC in different prefectures was found. The prevalence of HCV-1b in patients HCC was significantly higher than patients without HCC.The duration for the development of HCC was shorted in HCV-1b than the other subtypes of HCV., These results suggest that the oncogenecity of HCV-1b may be stronger than the other subtypes of HCV. Less