Division of Endocrinology & Metabolism, Department of Medicine, University of Ottawa, Ottawa, ON K1H 8L6, Canada.
Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.
Cells. 2019 Mar 15;8(3):252. doi: 10.3390/cells8030252.
Chronic hepatitis C (HCV) infection perturbs lipid and glucose metabolism. The influenceof direct acting antiviral (DAA) treatment and ribavirin on these measures was evaluated.Furthermore, the effect of HCV cure on these parameters was assessed. Participants were allocatedto one of three 12-week treatment groups: non-cirrhotic genotype 1aparitaprevir/ritonavir/ombitasvir/dasabuvir (PrOD) plus ribavirin; non-cirrhotic 1b-PrOD;compensated cirrhotic 1a or 1b-PrOD plus ribavirin. Fasting insulin, glucose, lipid andapolipoprotein measures were assessed at baseline, Treatment Weeks 4 and 12, and 12 and 24 weekspost-dosing. Twenty-three of 24 participants achieved SVR (PP= 23/24, 96% SVR). Overall, totalcholesterol, low-density lipoprotein cholesterol (LDL-C), and triglyceride levels all increased intreatment and post-dosing. However, LDL-C levels decreased during treatment in ribavirinrecipients. Fasting glucose, insulin, and HOMA-IR were unchanged during treatment and 12 weekspost-treatment. By 12 weeks post-treatment, controlled attenuation parameter (CAP) scores, ameasure of steatosis, increased from baseline (mean 30.3 ± 63.5, p = 0.05). This regimen was safe andhighly effective and did not influence glucose metabolism. Ribavirin exposure may mitigate someon-treatment lipid changes. Further mechanistic studies are needed to understand how ribavirinimpacts lipid pathways, as there could be therapeutic implications. The metabolic pathophysiologyof increased CAP score with HCV treatment requires explanation.
慢性丙型肝炎(HCV)感染会扰乱脂质和葡萄糖代谢。评估了直接作用抗病毒(DAA)治疗和利巴韦林对这些措施的影响。此外,还评估了 HCV 治愈对这些参数的影响。参与者被分配到三个 12 周治疗组之一:非肝硬化基因型 1a 阿帕利帕韦/利托那韦/奥比他韦/达沙布韦(PrOD)加利巴韦林;非肝硬化 1b-PrOD;代偿性肝硬化 1a 或 1b-PrOD 加利巴韦林。在基线、治疗第 4 和 12 周以及停药后 12 和 24 周时评估空腹胰岛素、血糖、脂质和载脂蛋白测量值。24 名参与者中有 23 名(PP=23/24,96% SVR)达到 SVR。总体而言,总胆固醇、低密度脂蛋白胆固醇(LDL-C)和甘油三酯水平在治疗和停药后均升高。然而,利巴韦林组在治疗过程中 LDL-C 水平下降。治疗期间和治疗后 12 周,空腹血糖、胰岛素和 HOMA-IR 均未发生变化。治疗后 12 周,脂肪肝衰减参数(CAP)评分(平均 30.3 ± 63.5,p=0.05)从基线开始增加。该方案安全且高效,不会影响葡萄糖代谢。利巴韦林暴露可能减轻一些治疗中的脂质变化。需要进一步的机制研究来了解利巴韦林如何影响脂质途径,因为这可能具有治疗意义。HCV 治疗后 CAP 评分增加的代谢病理生理学需要解释。