Hepatology Unit. Department of Medical and Surgical Sciences, University of Bologna and Sant'Orsola-Malpighi Hospital, Bologna, Italy.
Internal Medicine Unit. Department of Medical and Surgical Sciences, University of Bologna and Sant'Orsola-Malpighi Hospital, Bologna, Italy.
Ann Hepatol. 2018 January-February;17(1):64-75. doi: 10.5604/01.3001.0010.7536.
Host lipid metabolism influences viral replication and lifecycle of hepatitis C virus. Our aim was to evaluate changes in glucose and lipid metabolism of patients with chronic hepatitis C after therapy with direct acting antivirals (DAA).
We considered patients consecutively treated between January and November 2015 recording clinical data at baseline and week 24 of follow-up. Frozen serum samples were used for apolipoprotein A1 (apoA1), apolipoprotein B (apoB) and lipoprotein (a) [Lp(a)]. Wilcoxon test was utilized to estimate trends and Logistic Regression for predictors of lipid changes.
We enrolled 100 patients, mostly cirrhotic (81%) and with genotype 1b (59%). Ninety-three patients achieved sustained virological response (SVR), while 7 relapsed. Homeostasis model assessment of insulin resistance declined (from 3 to 2.7, p < 0.001); non-high density lipoprotein (HDL) cholesterol increased from 102 ± 29 to 116 ± 35 (p < 0.001), and Lp(a) from 5.6 ± 6.5 to 9.8 ± 11.5 mg/dL (p < 0.001). Rise of low-density lipoprotein/HDL and apoB/apoA1 ratio were registered (from 1.79 ± 1.10 to 2.08 ± 1.05 and from 0.48 ± 0.18 to 0.53 ± 0.18 mg/dL, p < 0.001). We conducted a subanalysis on patients with relapse. In this subgroup, no change of lipid profile was recorded. At multivariate analysis emerged that the addition of ribavirin to DAA, represented an independent predictor of increased Lp(a) (OR 3.982, 95% CI 1.206-13.144, p = 0.023).
DAA therapy led to reduction of insulin resistance. In contrast, pro-atherogenic lipid changes were observed in patients with SVR. Further studies will be necessary to evaluate the cardiovascular balance between amelioration of glucose metabolism and negative changes of lipid profile.
宿主的脂质代谢影响丙型肝炎病毒的复制和生命周期。我们的目的是评估直接作用抗病毒药物（DAA）治疗后慢性丙型肝炎患者的葡萄糖和脂质代谢变化。
我们连续纳入了 2015 年 1 月至 11 月间接受治疗的患者，记录基线和随访 24 周时的临床数据。使用冰冻血清样本检测载脂蛋白 A1（apoA1）、载脂蛋白 B（apoB）和脂蛋白（a）[Lp(a)]。采用 Wilcoxon 检验评估趋势，应用 Logistic 回归分析预测脂质变化的因素。
我们共纳入了 100 例患者，大多数为肝硬化（81%）且基因型为 1b（59%）。93 例患者获得持续病毒学应答（SVR），7 例复发。胰岛素抵抗的稳态模型评估值下降（从 3 降至 2.7，p < 0.001）；非高密度脂蛋白（HDL）胆固醇从 102±29 增加至 116±35（p < 0.001），Lp(a)从 5.6±6.5 增加至 9.8±11.5mg/dL（p < 0.001）。记录到低密度脂蛋白/HDL 和 apoB/apoA1 比值的升高（从 1.79±1.10 增加至 2.08±1.05 和从 0.48±0.18 增加至 0.53±0.18mg/dL，p < 0.001）。我们对复发患者进行了亚组分析。在此亚组中，未记录到脂质谱的变化。多变量分析显示，DAA 联合利巴韦林治疗是 Lp(a)升高的独立预测因素（OR 3.982，95%CI 1.206-13.144，p = 0.023）。
DAA 治疗可降低胰岛素抵抗。相反，SVR 患者观察到致动脉粥样硬化的脂质变化。需要进一步研究以评估改善葡萄糖代谢与脂质谱负面变化之间的心血管平衡。
