Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
Hepatology. 2010 Sep;52(3):854-63. doi: 10.1002/hep.23796.
Approximately one half of patients who undergo antiviral therapy for chronic hepatitis C virus (HCV) genotype 1 infection do not respond to treatment. African Americans (AAs) are less responsive to treatment than Caucasian Americans (CAs), but the reasons for this disparity are largely unknown. Recent studies suggest that serum lipids may be associated with treatment response. The aims of this study were to evaluate baseline and changes in serum lipids during therapy, determine whether serum lipids are associated with virological response, and assess whether these measures explain the racial difference in efficacy. The study participants were from Virahep-C, a prospective study of treatment-naïve patients with genotype 1 HCV infection who received peginterferon (PEG-IN) alfa-2a plus ribavirin therapy for up to 48 weeks. Fasting serum lipids were analyzed at baseline and during and after therapy in 160 AAs and 170 CAs. A relative risk (RR) model was employed to evaluate characteristics associated with sustained virological response (SVR). Antiviral therapy was associated with changes in serum lipids during and after antiviral therapy, with the changes differing by race and the amount of PEG-IFN taken. Baseline lipid measures independently associated with higher rates of SVR were lower triglyceride and higher low-density lipoprotein cholesterol, with an interaction between high-density lipoprotein cholesterol (HDLc) and gender. Lipid measures did not contribute significantly to an explanation of the racial difference in SVR.
Serum lipids are associated with SVR, although these paramaters did not explain the racial difference in treatment response. The results of this study are compatible with proposed biological mechanisms of HCV entry, replication, and secretion, and may underscore new potential therapeutic targets for HCV eradication.
大约一半接受慢性丙型肝炎病毒（HCV）基因型 1 感染抗病毒治疗的患者对治疗无反应。非裔美国人（AAs）对治疗的反应不如白种美国人（CAs），但造成这种差异的原因在很大程度上尚不清楚。最近的研究表明，血清脂质可能与治疗反应有关。本研究的目的是评估治疗前和治疗过程中血清脂质的变化，确定血清脂质是否与病毒学应答相关，并评估这些措施是否可以解释疗效的种族差异。研究参与者来自 Virahep-C，这是一项针对初治基因型 1 HCV 感染患者的前瞻性研究，这些患者接受聚乙二醇干扰素（PEG-IN）alfa-2a 联合利巴韦林治疗，疗程长达 48 周。在 160 名 AAs 和 170 名 CAs 中，在基线和治疗期间及治疗后检测空腹血清脂质。采用相对风险（RR）模型评估与持续病毒学应答（SVR）相关的特征。抗病毒治疗与治疗期间和治疗后血清脂质的变化有关，这种变化因种族和所用 PEG-IFN 的量而异。与 SVR 率较高独立相关的基线脂质指标是较低的甘油三酯和较高的低密度脂蛋白胆固醇，高密度脂蛋白胆固醇（HDLc）与性别之间存在交互作用。脂质指标对 SVR 种族差异的解释没有显著贡献。
血清脂质与 SVR 相关，尽管这些参数不能解释治疗反应的种族差异。本研究的结果与 HCV 进入、复制和分泌的拟议生物学机制一致，可能突出了 HCV 消除的新的潜在治疗靶点。
