Sugihara Kanji, Orito Etsuro, Tanaka Yasuhito, Kato Takanobu, Lau Johnson Y N, Ohno Tomoyoshi, Hayashi Katsuo, Ogino Masataka, Hirashima Noboru, Sakakibara Kenji, Mizuno Yoshiki, Kato Hideaki, Suzuki Seiji, Ueda Ryuzo, Mizokami Masashi
Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, and Department of Gastroenterology, Nagoya Daini Red Cross Hospital, Japan.
Intervirology. 2006;49(6):319-26. doi: 10.1159/000095151. Epub 2006 Aug 21.
A recent study suggested that the substitution of amino acid 415 of HCV NS5B from phenylalanine to tyrosine in patients with HCV genotype 1a infection is induced by ribavirin and responsible for resistance to ribavirin therapy. The aim of this study was to evaluate whether specific variations in the HCV NS5B sequence in Japanese patients with HCV genotype 1b (HCV/1b) infection are associated with treatment response or selected by treatment with interferon-alpha/ribavirin combination therapy.
Eighteen Japanese patients with HCV/1b infection receiving interferon-alpha/ribavirin combination therapy for 24 weeks were studied. Five patients treated with interferon-alpha monotherapy for 24 weeks were also studied as controls. The entire HCV NS5B sequence before and after therapy was determined.
All HCV isolates had tyrosine at position 415 of NS5B before and after therapy. Further analysis showed that no specific amino acid substitutions were identified to associate with clinical response and no specific amino acid substitutions were induced/selected by the clinical treatment.
No specific HCV NS5B nucleotide/amino acid sequence variations, including amino acid 415 of NS5B, were identified as being associated with clinical treatment response or selected by the combination therapy in Japanese patients with HCV/1b infection.
最近一项研究表明,丙型肝炎病毒(HCV)1a基因型感染患者中,HCV NS5B的415位氨基酸由苯丙氨酸替换为酪氨酸是由利巴韦林诱导产生的,并且与利巴韦林治疗耐药有关。本研究的目的是评估日本丙型肝炎病毒1b基因型(HCV/1b)感染患者中HCV NS5B序列的特定变异是否与治疗反应相关,或者是否是由α干扰素/利巴韦林联合治疗所选择的。
对18例接受α干扰素/利巴韦林联合治疗24周的日本HCV/1b感染患者进行研究。还对5例接受α干扰素单药治疗24周的患者作为对照进行研究。测定治疗前后的整个HCV NS5B序列。
所有HCV分离株在治疗前后NS5B的415位均为酪氨酸。进一步分析表明,未发现与临床反应相关的特定氨基酸替换,临床治疗也未诱导/选择出特定的氨基酸替换。
在日本HCV/1b感染患者中,未发现包括NS5B的415位氨基酸在内的特定HCV NS5B核苷酸/氨基酸序列变异与临床治疗反应相关,也未发现其是由联合治疗所选择的。