Inoue Jun, Kanno Atsushi, Wakui Yuta, Miura Masahito, Kobayashi Tomoo, Morosawa Tatsuki, Kogure Takayuki, Kakazu Eiji, Ninomiya Masashi, Fujisaka Yasuyuki, Umetsu Teruyuki, Takai Satoshi, Nakamura Takuya, Shimosegawa Tooru
Division of Gastroenterology, Tohoku University Graduate School of Medicine.
Tohoku J Exp Med. 2017 Jan;241(1):21-28. doi: 10.1620/tjem.241.21.
It is important to determine the genotypes or serotypes of hepatitis C virus (HCV) in patients before treatment with direct-acting antiviral agents (DAAs), because the effects of DAAs differ among genotypes. In Japan, two tests for HCV typing are available clinically, but only serotyping, not genotyping, is approved by the public health insurance. Although most serotype-1 Japanese patients are infected with genotype 1b HCV, it is known that a small proportion of patients show different results from two typing methods. This study focused on such patients and the effectiveness of treatment with daclatasvir plus asunaprevir (DCV/ASV) was evaluated. We analyzed 644 DCV/ASV-treated patients with serotype 1 or genotype 1b, and among them, 166 serotype-1 patients received a commercial-based direct sequencing (DS) test for resistant-associated variants of genotype 1b HCV. We found four patients (2.4%) with DS test failure, suggesting that the PCR primers targeting genotype 1b may not match. Importantly, none of the four patients achieved a sustained virological response. Our in-house DS test analyzing the 5'-untranslated region and coding regions for NS4 and NS5B of HCV showed that three of the four patients were infected with genotype 2 HCV, and one patient was infected with genotype 1a HCV. No recombinant virus of different genotypes was found. This study indicates that a subset of serotype-1 hepatitis C patients is infected with HCV of genotype 2 or 1a in Japan and that DCV/ASV is not effective for such patients. Thus, attention should be paid to DAA treatment without HCV genotyping.
在使用直接抗病毒药物（DAA）治疗丙型肝炎病毒（HCV）患者之前，确定其HCV基因型或血清型很重要，因为DAA对不同基因型的疗效不同。在日本，临床上有两种HCV分型检测方法，但只有血清分型而非基因分型被公共医疗保险批准。尽管大多数血清型1的日本患者感染的是1b型HCV，但已知一小部分患者两种分型方法的结果不同。本研究聚焦于这类患者，并评估了达卡他韦联合阿舒瑞韦（DCV/ASV）治疗的有效性。我们分析了644例接受DCV/ASV治疗的血清型1或1b型患者，其中166例血清型1患者接受了基于商业的1b型HCV耐药相关变异的直接测序（DS）检测。我们发现4例患者（2.4%）DS检测失败，提示靶向1b型的PCR引物可能不匹配。重要的是，这4例患者均未实现持续病毒学应答。我们对HCV的5'-非翻译区以及NS4和NS5B编码区进行分析的内部DS检测显示，4例患者中有3例感染了2型HCV，1例患者感染了1a型HCV。未发现不同基因型的重组病毒。本研究表明，在日本，一部分血清型1的丙型肝炎患者感染的是2型或1a型HCV，且DCV/ASV对这类患者无效。因此，在未进行HCV基因分型的情况下应注意DAA治疗。
