Ribavirin dose reduction during telaprevir/ribavirin/peg-interferon therapy overcomes the effect of the ITPA gene polymorphism.
Ribavirin dose reduction during telaprevir/ribavirin/peg-interferon therapy overcomes the effect of the ITPA gene polymorphism.
复制标题
特拉匹韦/利巴韦林/聚乙二醇干扰素治疗期间利巴韦林剂量的减少克服了 ITPA 基因多态性的影响。
DOI：
10.1111/jvh.12275
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Chayama K; Hiroshima Liver Study Group.
中科院分区：
文献类型：
--
作者：
Akamatsu S;Hayes CN;Tsuge M;Murakami E;Hiraga N;Abe H;Miki D;Imamura M;Ochi H;Chayama K; Hiroshima Liver Study Group.
随着特拉匹韦加聚乙二醇干扰素/利巴韦林三联疗法的出现，慢性丙型肝炎病毒基因型1感染的治疗成功率有所提高。然而，肌苷三磷酸酶（ITPA）多态性对三联治疗期间剂量减少的影响，特别是在上市后阶段，尚未得到充分评价。我们分析了273例接受三联疗法治疗的基因型1感染患者，并评估了ITPA多态性对剂量减少的影响。ITPA和IFNL 4 SNP基因型通过Invader测定确定。采用逐步多元回归分析确定与治疗结果相关的因素。治疗结束后12周的总体持续病毒应答（SVR）率为80.2%（219/273）。与CA/AA相比，ITPA SNP rs 1127354基因型CC患者的血红蛋白下降明显更快，利巴韦林的减少更广泛。利巴韦林的广泛减少导致特拉匹韦和聚乙二醇干扰素的轻度减少，但病毒突破没有显著增加。尽管CA/AA患者的特拉匹韦用量略高，但两组之间的聚乙二醇干扰素总剂量和SVR率没有差异。多变量分析显示，IFNL 4而非ITPA SNP基因型、血小板计数和PEG干扰素依从性与治疗结局显著相关。尽管在不同患者人群中广泛降低了利巴韦林剂量，但上市后阶段三联疗法导致高SVR率，表明继续治疗和适当管理不良事件的重要性。
Treatment success of chronic hepatitis C virus genotype 1 infection has improved with the advent of telaprevir plus peg‐interferon/ribavirin triple combination therapy. However, the effect of inosine triphosphatase (ITPA) polymorphism on dose reduction during triple therapy, especially during the postmarketing phase, has not been sufficiently evaluated. We analysed 273 patients with genotype 1 infection who were treated with triple therapy and assessed the effect of the ITPA polymorphism on dose reduction. ITPA and IFNL4 SNP genotypes were determined by the Invader assay. A stepwise multivariate regression analysis was performed to identify factors associated with outcome of the therapy. The overall sustained viral response (SVR) rate 12 weeks after the end of therapy was 80.2% (219/273). Decline of haemoglobin was significantly faster, and ribavirin was more extensively reduced in patients with ITPA SNP rs1127354 genotype CC than CA/AA. Extensive reduction of ribavirin resulted in mild reduction of telaprevir and peg‐interferon, but no significant increase in viral breakthrough. Although the amount of telaprevir given was slightly higher in CA/AA patients, the total dose of peg‐interferon and the SVR rate did not differ between the two groups. Multivariate analysis showed that IFNL4 but not ITPA SNP genotype, platelet count and peg‐interferon adherence were significantly associated with outcome of therapy. Postmarketing‐phase triple therapy resulted in a high SVR rate in spite of extensive ribavirin dose reduction in a diverse patient population, indicating the importance of treatment continuation and appropriate management of adverse events.