Pedersen Mark R, Patel Amit, Backstedt David, Choi Myunghan, Seetharam Anil B
Mark R Pedersen, Department of Internal Medicine, Banner University Medical Center, University of Arizona College of Medicine, Phoenix, AZ 85006, United States.
World J Gastroenterol. 2016 Dec 14;22(46):10226-10231. doi: 10.3748/wjg.v22.i46.10226.
To evaluate magnitude/direction of changes in peripheral lipid profiles in patients undergoing direct acting therapy for hepatitis C by genotype.
Mono-infected patients with hepatitis C were treated with guideline-based DAAs at a university-based liver clinic. Patient characteristics and laboratory values were collected before and after the treatment period. Baseline demographics included age, ethnicity, hypertension, diabetes, hyperlipidemia, treatment regimen, and fibrosis stage. Total cholesterol (TCHOL), high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides (TG), and liver function tests were measured prior to treatment and ETR. Changes in lipid and liver function were evaluated by subgroups with respect to genotype. Mean differences were calculated for each lipid profile and liver function component (direction/magnitude). The mean differences in lipid profiles were then compared between genotypes for differences in direction/magnitude. Lipid profile and liver function changes were evaluated with Levene's test and student's test. Mean differences in lipid profiles were compared between genotypes using ANOVA, analysis the Bonferroni correction or Dunnett T3.
Three hundred and seventy five patients enrolled with 321 (85.6%) achieving sustained-viral response at 12 wk. 72.3% were genotype 1 (GT1), 18.1% genotype 2 (GT2), 9.7% genotype 3 (GT3). Baseline demographics were similar. Significant change in lipid profiles were seen with GT1 and GT3 (ΔGT1, p and ΔGT3, p), with TCHOL increasing (+5.3, = 0.005 and +16.1, < 0.001), HDL increasing (+12.5, < 0.001 and +7.9, = 0.038), LDL increasing (+7.4, = 0.058 and +12.5, < 0.001), and TG decreasing (-5.9, = 0.044 and -9.80 = 0.067). Among genotypes (ΔGT1 v. ΔGT2 v. ΔGT3, ANOVA), significant mean differences were seen with TCHOL (+5.3 v. +0.1 v. +16.1, = 0.017) and HDL (+12.3 v. +2 v. +7.9, = 0.040). Post-hoc, GT3 was associated with a greater increase in TCHOL than GT1 and GT2 ( = 0.028 and = 0.019).
Successful DAA therapy results in increases in TCHOL, LDL, and HDL and decrease in TG, particularly in GT1/GT3. Changes are most pronounced in GT3.
按基因型评估接受丙型肝炎直接作用疗法的患者外周血脂谱变化的幅度/方向。
在一家大学肝病诊所，对单感染丙型肝炎患者采用基于指南的直接抗病毒药物（DAA）进行治疗。在治疗前后收集患者特征和实验室值。基线人口统计学数据包括年龄、种族、高血压、糖尿病、高脂血症、治疗方案和纤维化阶段。在治疗前和评估治疗结束时病毒学应答（ETR）前测量总胆固醇（TCHOL）、高密度脂蛋白（HDL）、低密度脂蛋白（LDL）、甘油三酯（TG）和肝功能测试。按基因型亚组评估血脂和肝功能变化。计算每种血脂谱和肝功能成分的平均差异（方向/幅度）。然后比较各基因型之间血脂谱平均差异的方向/幅度差异。采用Levene检验和学生检验评估血脂谱和肝功能变化。使用方差分析（ANOVA）、分析（ANOVA）及Bonferroni校正或Dunnett T3比较各基因型之间的血脂谱平均差异。
375例患者入组，321例（85.6%）在12周时实现持续病毒学应答。72.3%为基因1型（GT1），18.1%为基因2型（GT2），9.7%为基因3型（GT3）。基线人口统计学数据相似。GT1和GT3患者的血脂谱有显著变化（ΔGT1，p值和ΔGT3，p值），TCHOL升高（分别为+5.3，p = 0.005和+16.1，p < 0.001），HDL升高（分别为+12.5，p < 0.001和+7.9，p = 0.038），LDL升高（分别为+7.4，p = 0.058和+12.5，p < 0.001），TG降低（分别为-5.9，p = 0.044和-9.80，p = 0.067）。在各基因型之间（ΔGT1对ΔGT2对ΔGT3，ANOVA），TCHOL（分别为+5.3对+0.1对+16.1，p = 0.017）和HDL（分别为+12.3对+2对+7.9，p = 0.040）存在显著平均差异。事后分析显示，GT3患者的TCHOL升高幅度大于GT1和GT2患者（p = 0.028和p = 0.019）。
成功的DAA治疗可导致TCHOL、LDL和HDL升高以及TG降低，尤其是在GT1/GT3患者中。GT3患者的变化最为明显。
