Yee Leland J, Im KyungAh, Wahed Abdus S, Bugawan Teodorica, Li Jia, Rhodes Shannon L, Erlich Henry, Rosen Hugo R, Liang T Jake, Yang Huiying
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pennsylvania 15261, USA.
Antimicrob Agents Chemother. 2009 Feb;53(2):615-21. doi: 10.1128/AAC.00947-08. Epub 2008 Oct 13.
The dynamics of the viral decline immediately after the start of therapy for chronic hepatitis C virus (HCV) infection may have prognostic potential for ultimate sustained virologic response. Considerable interindividual variability in the decline has been reported, including differences by race. The human major histocompatability complex (MHC) genes encode the human leukocyte antigens, which are important in the immune response to viral infections. We examined whether carriage of specific human MHC alleles are associated with the rate of the early viral decline. Longitudinal viral level data (baseline and days 1, 2, 7, 14, and 28 of treatment), medium resolution MHC genotyping, and random coefficients models were used to examine associations between MHC class I and class II allele carriage and the dynamics of the viral decline in 180 African-Americans (AAs) and 194 Caucasian Americans (CAs) with genotype-1 HCV infection over the first 28 days of treatment with peginterferon alpha2a plus ribavirin. Baseline viral levels were similar by race, irrespective of allele carriage. However, the rate of change in the viral decline was associated with both allele and race. Among the four subgroups defined by race and specific allele, the fastest rates of decline were observed (in terms of estimated mean viral declines log(10) IU/ml during the first four weeks) in CA noncarriers for A03 (2.75; P = 0.018), in CA carriers for Cw03 (2.99; P = 0.046), and in CA noncarriers for DQA104 (2.66; P = 0.018) or DQB10402 (2.65; P = 0.018). MHC alleles are associated with the viral decline during the first 28 days of peginterferon therapy.
慢性丙型肝炎病毒（HCV）感染开始治疗后病毒载量立即下降的动态变化可能对最终的持续病毒学应答具有预后潜力。据报道，病毒载量下降存在相当大的个体差异，包括种族差异。人类主要组织相容性复合体（MHC）基因编码人类白细胞抗原，其在病毒感染的免疫应答中起重要作用。我们研究了特定人类MHC等位基因的携带情况是否与早期病毒载量下降速率相关。利用纵向病毒载量数据（基线以及治疗第1、2、7、14和28天的数据）、中等分辨率MHC基因分型以及随机系数模型，研究了180名非裔美国人（AAs）和194名高加索裔美国人（CAs）在接受聚乙二醇干扰素α2a加利巴韦林治疗的前28天内，MHC I类和II类等位基因携带情况与病毒载量下降动态变化之间的关联。无论等位基因携带情况如何，不同种族的基线病毒载量相似。然而，病毒载量下降的变化速率与等位基因和种族均相关。在由种族和特定等位基因定义的四个亚组中，观察到下降速率最快的情况（就前四周估计的平均病毒载量下降log(10) IU/ml而言）：A03的CA非携带者（2.75；P = 0.018）、Cw03的CA携带者（2.99；P = 0.046）以及DQA104（2.66；P = 0.018）或DQB10402（2.65；P = 0.018）的CA非携带者。MHC等位基因与聚乙二醇干扰素治疗的前28天内病毒载量下降相关。
