Establishment of predictors in treatment response of chronic hepatitisC by mutational analysis of internal ribosome entry site within hepatitis C virus

进行了聚乙二醇化干扰素和利巴韦林的联合治疗（以下，PEG/RBV治疗），并分析了60例或更多的慢性丙型肝炎（以下，CH-C）病例，包括应答者、无应答者和复发者。在每种情况下，对HCV RNA的内部核糖体进入位点（IRES）区域的基因突变进行分析。在无应答组中，许多病例有既往干扰素治疗史，并且在这些病例中，许多病例在IRES结构域III（以下，d III）区域没有突变。另一方面，在应答病例中，有许多病例有IRES d III突变的趋势（P<0.05）。换句话说，这表明由于先前的抗病毒治疗而产生的耐药HCV可能正在被选择。在复发病例中，当对治疗结束时从血清中克隆的IRES碱基突变进行分析时（当阴性时，通过市售HCV RNA定性方法），发现在IRES区域的碱基119中存在特征性突变。在PEG/RBV治疗的无应答组和应答组中，当比较IRES碱基119突变时，在两组之间观察到差异，并且发现与HCV核心区突变相关。换句话说，HCV IRES碱基突变和核心突变之间的关系与治疗结果之间存在相关性。在寻找作为病毒因素的耐药机制中，这被认为是一个重要的发现。

Combination therapy with pegylated interferon and ribavirin (below, PEG/RBV treatment) was performed, and 60 or more cases of Chronic Hepatitis C (below, CH-C), resulting in responders, non-responders and relapsers, were analyzed. An analysis was performed ofthe genetic mutation in the internal ribosome entry site (below, IRES) area of the HCV RNA in each case. In the non-response group, many cases had a history of previous interferon therapy, and in those cases, many cases had no mutations in the IRES domain III (below, d III) area. On the other hand, in the response cases, there was a tendency (P<0.05) for many cases to have mutation in IRES d III. In other words, this indicates that there is a possibility that resistant HCV due to previous antiviral therapy is being selected. In the relapse cases, when an analysis was performed of the IRES base mutation cloned from blood serum at the conclusion of treatment (when negative, by a commercially available HCV RNA qualitative metho), it was found that there was a characteristic mutation in base 119 in the IRES area. In the non-response group and response group for PEG/RBV treatment, when IRES base 119 mutations were compared, a discrepancy was observed between both groups, and furthermore, a correlation was found with HCV core area mutations. In other words, a correlation was indicated between the relationship between HCV IRES base mutations and core mutations, and the treatment results. In the search for thetreatment resistant mechanism as a viral factor, this is believed to be an important finding.