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丙型肝炎病毒(HCV)抗病毒治疗对血脂水平的影响。

Effect of antiviral therapy for HCV on lipid levels.

作者信息

Mauss Stefan, Berger Florian, Wehmeyer Malte H, Ingiliz Patrick, Hueppe Dietrich, Lutz Thomas, Simon Karl G, Schewe Knud, Rockstroh Juergen K, Baumgarten Axel, Christensen Stefan

机构信息

Center for HIV and Hepatogastroenterology, Duesseldorf, Germany.

Department of Medicine I, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

出版信息

Antivir Ther. 2017;21(1):81-88. doi: 10.3851/IMP3094. Epub 2016 Sep 29.

Abstract

BACKGROUND

HCV has complex interactions with human lipid metabolism leading to down regulation of cholesterol levels. Interferon (IFN) therapy has been shown to decrease cholesterol even further. With the availability of second-generation direct-acting antiviral agents (DAA) the effect of suppressing and eliminating HCV on lipid metabolism warrants reevaluation.

METHODS

Prospective German multicentre cohort on HCV- and HIV-HCV-infected patients treated with direct-antiviral agents (GECCO). Lipids were assessed at baseline, during and after therapy. Wilcoxon test corrected for multiple testing was used.

RESULTS

For the analysis, 520 patients with chronic hepatitis C were available. Patients with chronic hepatitis C were treated as follows: sofosbuvir (SOF)/pegylated IFN (PEG-IFN)/ribavirin (RBV; HCV=34, HIV-HCV=36), SOF/RBV (HCV=47, HIV-HCV=16), SOF/simeprevir (HCV=9, HCV-HIV=2), SOF/daclatasvir +/- RBV (HCV=27, HIV-HCV=47), SOF/ledipasvir +/- RBV (HCV=147, HCV-HIV=100) and ombitasvir/paritaprevir/ritonavir +/- dasabuvir +/- RBV (2D, HCV=2, HCV-HIV=6; 3D, HCV=39, HCV-HIV=8). On treatment there was a statistically significant increase in total cholesterol for any IFN-free DAA regimen, which was maintained after end of therapy. Changes of total cholesterol were driven by changes in low-density lipoprotein cholesterol, whereas high-density lipoprotein cholesterol remained unchanged. In contrast, total cholesterol decreased on SOF/PEG-IFN/RBV and increased after end of therapy above baseline levels. Triglycerides increased during treatment with SOF/PEG-IFN/RBV, but not on DAA-only regimens.

CONCLUSIONS

Suppressing and eliminating HCV with IFN-free DAA regimens increased cholesterol levels, but had no effect on triglycerides. In contrast IFN-based therapy decreased cholesterol and increased triglycerides during treatment and led to increases in cholesterol after achieving sustained virological response.

摘要

背景

丙型肝炎病毒(HCV)与人类脂质代谢存在复杂的相互作用,导致胆固醇水平下调。干扰素(IFN)治疗已被证明会使胆固醇进一步降低。随着第二代直接抗病毒药物(DAA)的出现,抑制和消除HCV对脂质代谢的影响值得重新评估。

方法

德国前瞻性多中心队列研究,纳入接受直接抗病毒药物治疗的HCV感染患者和HIV-HCV合并感染患者(GECCO)。在基线、治疗期间和治疗后评估脂质水平。采用经多重检验校正的Wilcoxon检验。

结果

分析纳入了520例慢性丙型肝炎患者。慢性丙型肝炎患者的治疗方案如下:索磷布韦(SOF)/聚乙二醇干扰素(PEG-IFN)/利巴韦林(RBV;HCV=34例,HIV-HCV=36例),SOF/RBV(HCV=47例,HIV-HCV=16例),SOF/西米普明(HCV=9例,HCV-HIV=2例),SOF/达卡他韦±RBV(HCV=27例,HIV-HCV=47例),SOF/来迪派韦±RBV(HCV=147例,HCV-HIV=100例)以及奥比他韦/帕利瑞韦/利托那韦±达沙布韦±RBV(2D方案,HCV=2例,HCV-HIV=6例;3D方案,HCV=39例,HCV-HIV=8例)。对于任何不含IFN的DAA方案,治疗期间总胆固醇有统计学意义的升高,且在治疗结束后仍维持升高。总胆固醇的变化由低密度脂蛋白胆固醇的变化驱动,而高密度脂蛋白胆固醇保持不变。相比之下,SOF/PEG-IFN/RBV治疗期间总胆固醇降低,治疗结束后升高至基线水平以上。使用SOF/PEG-IFN/RBV治疗期间甘油三酯升高,但仅使用DAA方案时甘油三酯无变化。

结论

使用不含IFN的DAA方案抑制和消除HCV会使胆固醇水平升高,但对甘油三酯无影响。相比之下,基于IFN的治疗在治疗期间会降低胆固醇并升高甘油三酯,且在实现持续病毒学应答后会使胆固醇升高。

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