三磷酸肌苷基因型与聚乙二醇干扰素和利巴韦林治疗后病毒应答延迟的丙型肝炎病毒患者延长治疗结局的关系。

Relationship between inosine triphosphate genotype and outcome of extended therapy in hepatitis C virus patients with a late viral response to pegylated-interferon and ribavirin.

机构信息

Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan.

出版信息

J Gastroenterol Hepatol. 2014 Jan;29(1):201-7. doi: 10.1111/jgh.12376.

DOI:10.1111/jgh.12376

PMID:23980585

Abstract

BACKGROUND AND AIM

It is not yet clear which factors are associated with the outcome of 72-week treatment with pegylated-interferon and ribavirin (RBV) in patients with chronic hepatitis C virus (HCV) infection.

METHODS

In 66 patients with HCV genotype 1 who had a late viral response (LVR) to 72-week treatment of pegylated-interferon and RBV, we examined the factors that determined the outcome, including single nucleotide polymorphisms of interleukin-28B and inosine triphosphatase (ITPA) genes.

RESULTS

Thirty seven of 66 (56%) patients with LVR achieved a sustained viral response (SVR). The mean age of these 37 SVR patients was 55, compared with 61 in 29 relapsed patients (P = 0.009). Twenty six of 54 (48%) patients with the CC genotype and 11 of 12 (92%) with the CA/AA genotype of ITPA rs1127354 achieved SVR (P = 0.006). The SVR rates were 79%, 40%, 60%, and 33% in patients with undetectable HCV RNA on weeks 16, 20, 24, and 28 or later, respectively (P = 0.014). Finally, serum RBV concentration at week 44 of treatment was significantly higher in the SVR group (2651 ng/mL) than in the relapse group (1989 ng/mL, P = 0.002). In contrast, the rate of the interleukin-28B genotype was not different between the groups. Multiple regression analysis showed that age < 60 years, ITPA CA/AA genotype, and serum RBV concentration were significant independent predictive factors for SVR.

CONCLUSIONS

Our findings elucidated the association of four factors, including ITPA genotype, with the outcome of 72-week treatment in LVR patients.

摘要

背景与目的

慢性丙型肝炎病毒（HCV）感染患者接受聚乙二醇干扰素和利巴韦林（RBV）72 周治疗的结局与哪些因素相关尚不清楚。

方法

在 66 例 HCV 基因 1 型对聚乙二醇干扰素和 RBV 72 周治疗发生晚期病毒学应答（LVR）的患者中，我们检测了决定结局的因素，包括白细胞介素 28B 和肌苷三磷酸酶（ITPA）基因的单核苷酸多态性。

结果

66 例 LVR 患者中，37 例（56%）获得持续病毒学应答（SVR）。37 例 SVR 患者的平均年龄为 55 岁，而 29 例复发患者的平均年龄为 61 岁（P=0.009）。ITPA rs1127354 位点 CC 基因型的 26 例和 CA/AA 基因型的 11 例患者均获得 SVR（P=0.006）。周 16、20、24 和 28 或更晚时 HCV RNA 不可检测的患者 SVR 率分别为 79%、40%、60%和 33%（P=0.014）。最后，治疗第 44 周时血清 RBV 浓度在 SVR 组（2651ng/mL）显著高于复发组（1989ng/mL，P=0.002）。相比之下，两组白细胞介素 28B 基因型的比例无差异。多因素回归分析显示，年龄＜60 岁、ITPA CA/AA 基因型和血清 RBV 浓度是 SVR 的显著独立预测因素。