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血清载脂蛋白 B-100 浓度可预测慢性丙型肝炎病毒 1b 基因型感染患者对聚乙二醇干扰素联合利巴韦林治疗的病毒学应答。

Serum apolipoprotein B-100 concentration predicts the virological response to pegylated interferon plus ribavirin combination therapy in patients infected with chronic hepatitis C virus genotype 1b.

机构信息

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University School of Medicine Katsushika Medical Center, Tokyo, Japan.

出版信息

J Med Virol. 2013 Jul;85(7):1180-90. doi: 10.1002/jmv.23597.

Abstract

Host lipoprotein metabolism is associated closely with the life cycle of hepatitis C virus (HCV), and serum lipid profiles have been linked to the response to pegylated interferon (Peg-IFN) plus ribavirin (RBV) therapy. Polymorphisms in the human IL28B gene and amino acid substitutions in the core and interferon sensitivity-determining region (ISDR) in NS5A of HCV genotype 1b (G1b) were also shown to strongly affect the outcome of Peg-IFN plus RBV therapy. In this study, an observational cohort study was performed in 247 HCV G1b-infected patients to investigate whether the response to Peg-IFN and RBV combination therapy in these patients is independently associated with the level of lipid factors, especially apolipoprotein B-100 (apoB-100), an obligatory structural component of very low density lipoprotein and low density lipoprotein. The multivariate logistic analysis subsequently identified apoB-100 (odds ratio (OR), 1.602; 95% confidence interval (CI), 1.046-2.456), alpha-fetoprotein (OR, 0.764; 95% CI, 0.610-0.958), non-wild-type ISDR (OR, 5.617; 95% CI, 1.274-24.754), and the rs8099917 major genotype (OR, 34.188; 95% CI, 10.225-114.308) as independent factors affecting rapid initial virological response (decline in HCV RNA levels by ≥3-log10 at week 4). While lipid factors were not independent predictors of complete early or sustained virological response, the serum apoB-100 level was an independent factor for sustained virological response in patients carrying the rs8099917 hetero/minor genotype. Together, we conclude that serum apoB-100 concentrations could predict virological response to Peg-IFN plus RBV combination therapy in patients infected with HCV G1b, especially in those with the rs8099917 hetero/minor genotype.

摘要

宿主脂蛋白代谢与丙型肝炎病毒 (HCV) 的生命周期密切相关,血清脂质谱与聚乙二醇干扰素 (Peg-IFN) 加利巴韦林 (RBV) 治疗的反应有关。人类 IL28B 基因的多态性和 HCV 基因型 1b (G1b) 的核心和干扰素敏感性决定区 (ISDR) 中的氨基酸取代也强烈影响 Peg-IFN 加 RBV 治疗的结果。在这项研究中,对 247 例 HCV G1b 感染患者进行了观察性队列研究,以调查这些患者对 Peg-IFN 和 RBV 联合治疗的反应是否与脂质因素水平独立相关,特别是载脂蛋白 B-100 (apoB-100),这是极低密度脂蛋白和低密度脂蛋白的必需结构成分。多变量逻辑分析随后确定了 apoB-100 (比值比 (OR),1.602;95%置信区间 (CI),1.046-2.456)、甲胎蛋白 (OR,0.764;95%CI,0.610-0.958)、非野生型 ISDR (OR,5.617;95%CI,1.274-24.754) 和 rs8099917 主要基因型 (OR,34.188;95%CI,10.225-114.308) 是影响快速初始病毒学应答 (第 4 周时 HCV RNA 水平下降≥3-log10) 的独立因素。虽然脂质因素不是完全早期或持续病毒学应答的独立预测因素,但在携带 rs8099917 杂合/次要基因型的患者中,血清 apoB-100 水平是持续病毒学应答的独立因素。综上所述,我们得出结论,血清 apoB-100 浓度可预测 HCV G1b 感染患者对 Peg-IFN 加 RBV 联合治疗的病毒学应答,尤其是在携带 rs8099917 杂合/次要基因型的患者中。

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