Predictors of viral kinetics to peginterferon plus ribavirin combination therapy in Japanese patients infected with hepatitis C virus genotype 1b
Predictors of viral kinetics to peginterferon plus ribavirin combination therapy in Japanese patients infected with hepatitis C virus genotype 1b
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DOI：
10.1002/jmv.20979
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发表时间：
2007-11-01
影响因子：
12.7
通讯作者：
Kumada, Hiromitsu
中科院分区：
文献类型：
--
作者：
Akuta, Norio;Suzuki, Fumitaka;Kumada, Hiromitsu
对于慢性丙型肝炎病毒（HCV）感染，基于病毒动力学评估对聚乙二醇干扰素（PEGIFN）加利巴韦林（RBV）治疗的反应可作为治疗效果的早期预测指标，但不同病毒动力学对治疗的潜在机制尚不清楚。在160名感染HCV基因型1b的日本成年患者中评估了48周PEG-IFN-RBV联合治疗的反应，并确定了快速病毒学反应（4周）、早期病毒学反应（12周）、治疗结束反应和持续病毒学反应（治疗结束后6个月）。表现出快速、早期和持续病毒学反应和治疗结束反应的患者比例分别为50%、73%、47%和71%。此外，66%获得早期病毒学应答的患者也表现出持续的病毒学应答。多变量分析发现，HCV核心区（双野生型）氨基酸（aa） 70和91的替换可作为早期HCV- rna阴性、快速、早期和持续病毒学反应和治疗结束反应的预测因子，而脂质代谢因子（高水平的LDL胆固醇和总胆固醇）可作为早期和快速病毒学反应和治疗结束反应的预测因子。男性和低水平的甲胎蛋白是持续病毒学反应的其他预测因素。此外，女性性别和肝纤维化的严重程度是缺乏持续病毒学反应的决定因素，尽管早期有病毒学反应。本研究基于日本HCV基因型1b感染患者的病毒动力学，确定了PEG-IFN-RBV治疗疗效的预测因子。
For chronic hepatitis C virus (HCV) infection, evaluation of response to peginterferon (PEGIFN) plus ribavirin (RBV) therapy based on viral kinetics is useful as an early predictor of treatment efficacy, but the underlying mechanisms of the different viral kinetics to treatment are still unclear. The response to 48-week PEG-IFN-RBV combination therapy was evaluated in 160 Japanese adult patients infected with HCV genotype 1b and determined the rapid virological response (at 4 weeks), early virological response (at 12 weeks), end-of treatment response, and sustained virological response (6 months after end of treatment). The proportion of patients who showed rapid, early and sustained virological, and end-of treatment responses were 50%, 73%, 47%, and 71%, respectively. Furthermore, 66% of patients who achieved early virological response also showed sustained virological response. Multivariate analysis identified substitutions of amino acid (aa) 70 and 91 in the HCV core region (double-wild-type) as a predictor of early HCV-RNA negativity, rapid, early, and sustained virological responses and end-of treatment response, and lipid metabolic factors (high levels of LDL cholesterol and total cholesterol) as predictors of early and rapid virological responses and end-of treatment response. Male sex and low levels of alpha-fetoprotein were other predictors of sustained virological response. Furthermore, female sex and severity of liver fibrosis were determinants of lack of sustained virological response in spite of early virological response. This study identified predictors of efficacy of PEG-IFN-RBV therapy based on viral kinetics in Japanese patients infected with HCV genotype 1 b.