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血清胆固醇和他汀类药物的使用预测聚乙二醇干扰素和利巴韦林治疗的病毒学应答。

Serum cholesterol and statin use predict virological response to peginterferon and ribavirin therapy.

机构信息

Department of Medicine, Brooke Army Medical Center, Fort Sam Houston, San Antonio, TX 78234, USA.

出版信息

Hepatology. 2010 Sep;52(3):864-74. doi: 10.1002/hep.23787.

Abstract

UNLABELLED

Elevated low-density lipoprotein (LDL) levels and statin use have been associated with higher sustained virological response (SVR) rates in patients receiving chronic hepatitis C therapy. However, these relationships have not been well characterized in randomized controlled trials. Furthermore, little is known about the relationship between high-density lipoprotein (HDL) and virological response. To determine whether baseline LDL or HDL levels and statin use affect SVR rates, we retrospectively evaluated the IDEAL (Individualized Dosing Efficacy Versus Flat Dosing to Assess Optimal Pegylated Interferon Therapy) trial, in which 3070 treatment-naive, hepatitis C virus (HCV) genotype 1-infected patients were treated for up to 48 weeks in one of the following arms: (1) peginterferon (PEG-IFN) alfa-2b at 1.5 microg/kg/week with ribavirin (RBV) at 800 to 1400 mg/day, (2) PEG-IFN alfa-2b at 1.0 microg/kg/week with RBV at 800 to 1400 mg/day, or (3) PEG-IFN alfa-2a at 180 microg/week with RBV at 1000 to 1200 mg/day. Virological responses were assessed by pretreatment statin use and baseline elevated LDL levels (> or =130 mg/dL) or low HDL levels (<40 mg/dL for men and <50 mg/dL for women). In 1464 patients with baseline elevated LDL levels or low HDL levels, the SVR rate was significantly higher than that in patients with normal levels (44.9% versus 34.0%, P < 0.001). In 66 patients receiving a statin pretreatment, the SVR rate was higher than the rate of those not receiving it (53.0% versus 39.3%, P = 0.02). In a multivariate logistic regression analysis using the stepwise selection method with baseline characteristics, a high LDL level [odds ratio (OR) = 1.6, 95% confidence interval (CI) = 1.4-1.8, P < 0.001], a low HDL level (OR = 0.5, 95% CI = 0.3-0.8, P = 0.004), and statin use (OR = 2.0, 95% CI = 1.1-3.7, P = 0.02) were independently associated with SVR.

CONCLUSION

Baseline elevated LDL levels or low HDL levels and preemptive statin usage were associated with higher SVR rates. Prospective studies may be considered to explore the biological impact of these factors on HCV RNA replication and treatment response.

摘要

目的

评估接受慢性丙型肝炎治疗的患者中,基线低密度脂蛋白(LDL)水平和他汀类药物使用与较高的持续病毒学应答(SVR)率之间的关系。

方法

我们回顾性地评估了 IDEAL (个体化剂量疗效与固定剂量评估聚乙二醇干扰素治疗的最佳剂量)试验,该试验纳入了 3070 例初治、丙型肝炎病毒(HCV)基因型 1 感染患者,这些患者接受以下治疗方案之一治疗 48 周:(1)1.5 μg/kg/周的聚乙二醇干扰素(PEG-IFN)α-2b 联合 800 至 1400mg/天的利巴韦林(RBV);(2)1.0μg/kg/周的 PEG-IFNα-2b 联合 800 至 1400mg/天的 RBV;(3)180μg/周的 PEG-IFNα-2a 联合 1000 至 1200mg/天的 RBV。通过预处理他汀类药物的使用以及基线时 LDL 水平升高(>130mg/dL)或 HDL 水平降低(男性<40mg/dL,女性<50mg/dL)来评估病毒学应答。在 1464 例基线 LDL 水平升高或 HDL 水平降低的患者中,SVR 率显著高于正常水平的患者(44.9%比 34.0%,P<0.001)。在 66 例接受他汀类药物预处理的患者中,SVR 率高于未接受他汀类药物预处理的患者(53.0%比 39.3%,P=0.02)。在使用逐步选择法的多变量逻辑回归分析中,采用基线特征,高 LDL 水平[比值比(OR)=1.6,95%置信区间(CI)=1.4-1.8,P<0.001]、低 HDL 水平(OR=0.5,95%CI=0.3-0.8,P=0.004)和他汀类药物的使用(OR=2.0,95%CI=1.1-3.7,P=0.02)与 SVR 独立相关。

结论

基线升高的 LDL 水平或低 HDL 水平以及预先使用他汀类药物与较高的 SVR 率相关。可能需要进行前瞻性研究以探索这些因素对 HCV RNA 复制和治疗反应的生物学影响。

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