Sarrafan-Chaharsoughi Zahra, Takyar Varun, Auh Sungyoung, Nee Gavin, Alawad Ahmad, Abel Brent S, Kapuria Devika, Byrnes Colleen, Wolska Anna, Kleiner David E, Shamburek Robert, Remaley Alan T, Ghany Marc G
Liver Diseases Branch, NIDDK, NIH, Bethesda, Maryland, USA.
Sutter East Bay Medical Foundation, Antioch, California, USA.
Aliment Pharmacol Ther. 2025 Jul;62(2):146-158. doi: 10.1111/apt.70130. Epub 2025 May 13.
Chronic hepatitis C virus (HCV) infection is associated with hypolipidemia. HCV eradication may, therefore, result in hyperlipidemia and increase cardiovascular disease (CVD) risk. We investigated the impact of HCV eradication on serum lipid and lipoprotein profiles and CVD risk during and following direct-acting antiviral (DAA) therapy.
We retrospectively analysed stored sera and plasma from 60 DAA-naïve patients, genotypes 1-4, treated with 12 weeks of sofosbuvir-velpatasvir. Serum lipids, apolipoproteins (apo), and a systemic inflammatory marker, GlycA, were measured serially beginning early on treatment and off treatment. Additionally, NMR LipoProfile analysis was performed on plasma samples. Expression of genes regulating lipid metabolism was assessed from paired liver biopsies obtained before and on treatment. Linear mixed models were used to examine changes in lipid and inflammatory markers; Framingham and ASCVD CVD risk scores were assessed before and after treatment. Decline in HCV viremia was associated with a rapid, significant increase in TChol, HDL-C, LDL-C, ApoA-1 and ApoB, and GlycA, improvement in ALT, hepatic inflammation, and steatosis but no change in glycemic control (HOMA-IR and HbA1c). Increase in TChol, LDL-C, and ApoB was associated with an increased SREBP1expression. Both ASCVD and Framingham risk scores were significantly increased at week 24 post treatment after adjusting for age (p < 0.0001).
Serum lipids and lipoproteins rapidly increase with inhibition of viral replication during DAA therapy, an effect that may be mediated by genes affecting hepatic de novo lipogenesis. Based on lipid changes, HCV eradication may increase CVD risk, but this needs to be investigated prospectively.
慢性丙型肝炎病毒（HCV）感染与血脂异常有关。因此，根除HCV可能会导致血脂升高并增加心血管疾病（CVD）风险。我们研究了在直接抗病毒（DAA）治疗期间及之后，根除HCV对血清脂质和脂蛋白谱以及CVD风险的影响。
我们回顾性分析了60例初治DAA患者（1-4型基因型）的储存血清和血浆，这些患者接受了12周的索磷布韦-维帕他韦治疗。从治疗早期开始直至治疗结束，连续检测血清脂质、载脂蛋白（apo）和一种全身炎症标志物GlycA。此外，对血浆样本进行了核磁共振脂蛋白谱分析。从治疗前和治疗时获取的配对肝脏活检组织中评估调节脂质代谢的基因表达。使用线性混合模型检查脂质和炎症标志物的变化；在治疗前后评估弗明汉和动脉粥样硬化性心血管疾病（ASCVD）的CVD风险评分。HCV病毒血症的下降与总胆固醇（TChol）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、载脂蛋白A-1（ApoA-1）和载脂蛋白B（ApoB）以及GlycA的快速、显著增加相关，丙氨酸氨基转移酶（ALT）、肝脏炎症和脂肪变性有所改善，但血糖控制（稳态模型评估胰岛素抵抗指数（HOMA-IR）和糖化血红蛋白（HbA1c））无变化。TChol、LDL-C和ApoB的增加与固醇调节元件结合蛋白1（SREBP1）表达增加相关。在调整年龄后，治疗后第24周时ASCVD和弗明汉风险评分均显著增加（p < 0.0001）。
在DAA治疗期间，随着病毒复制受到抑制，血清脂质和脂蛋白迅速升高，这种效应可能由影响肝脏从头脂肪生成的基因介导。基于脂质变化，根除HCV可能会增加CVD风险，但这需要进行前瞻性研究。
