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Favouring modulation of circulating lipoproteins and lipid loading capacity by direct antiviral agents grazoprevir/elbasvir or ledipasvir/sofosbuvir treatment against chronic HCV infection
Gut ( IF 24.5 ) Pub Date : 2017-06-14 , DOI: 10.1136/gutjnl-2017-313832
Hung-Yu Sun, Pin-Nan Cheng, Chiung-Ying Tseng, Wei-Jen Tsai, Yen-Cheng Chiu, Kung-Chia Young

Objective Lipid homoeostasis is disturbed in patients with HCV infection. Direct-acting antiviral agent (DAA) treatment eradicates chronic HCV viraemia, but the dynamics of lipid components remain elusive. This study investigates the clinical manifestation and mechanistic relevance of plasma triglyceride (TG), cholesterol (Chol), lipoproteins and apolipoproteins (apos) after DAA treatment. Design Twenty-four patients with chronic genotype 1 (GT1) HCV treated with elbasvir/grazoprevir or ledipasvir/sofosbuvir for 12 weeks, and followed-up thereafter, were recruited. Their TG, Chol, apoAI and apoB levels were quantified in plasma samples and individually fractionated lipoprotein of various classes. Liver fibrosis was evaluated using the FIB-4 Score. The TG and Chol loading capacities were calculated with normalisation to apoB, which represents per very low density lipoprotein (VLDL) and LDL particle unit Results DAA treatment achieved a sustained virological response rate of 91.7% and reduced the FIB-4 Score. Relative to the baseline, the plasma TG level was reduced but the Chol level increased gradually. Plasma apoB levels and apoB/apoAI ratio were transiently downregulated as early as the first 4 weeks of treatment. The TG and Chol loading capacities in VLDL were elevated by ~20% during the period of DAA treatment and had steadily increased by 100% at follow-up. Furthermore, the TG-to-Chol ratio in VLDL was increased, while the ratio in LDL was reduced, indicating an efficient catabolism. Conclusion The DAA treatment of patients with chronic hepatitis C might lead to efficient HCV eradication and hepatic improvement concomitantly evolving with favouring lipoprotein/apo metabolisms.

中文翻译:

通过直接抗病毒药物 grazoprevir/elbasvir 或 ledipasvir/sofosbuvir 治疗慢性 HCV 感染,有利于调节循环脂蛋白和脂质负荷能力

目的 HCV 感染患者的脂质稳态受到干扰。直接作用抗病毒剂 (DAA) 治疗可根除慢性 HCV 病毒血症,但脂质成分的动力学仍然难以捉摸。本研究调查了 DAA 治疗后血浆甘油三酯 (TG)、胆固醇 (Chol)、脂蛋白和载脂蛋白 (apos) 的临床表现和机制相关性。设计 招募了 24 名慢性基因型 1 (GT1) HCV 患者,他们接受了 elbasvir/grazoprevir 或 ledipasvir/sofosbuvir 治疗 12 周,随后进行了随访。他们的 TG、Chol、apoAI 和 apoB 水平在血浆样本中进行量化,并单独分级分离不同类别的脂蛋白。使用 FIB-4 评分评估肝纤维化。TG 和 Chol 负载能力通过标准化为 apoB 来计算,它代表每个极低密度脂蛋白 (VLDL) 和 LDL 颗粒单位 结果 DAA 治疗实现了 91.7% 的持续病毒学应答率并降低了 FIB-4 评分。相对于基线,血浆TG水平降低,但Chol水平逐渐升高。早在治疗的前 4 周,血浆 apoB 水平和 apoB/apoAI 比率就会短暂下调。在 DAA 治疗期间,VLDL 中的 TG 和 Chol 负荷能力提高了约 20%,并在随访期间稳步提高了 100%。此外,VLDL 中 TG 与 Chol 的比率增加,而 LDL 的比率降低,表明分解代谢有效。
更新日期:2017-06-14
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