The Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia.
Hepatology. 2014 Jan;59(1):109-20. doi: 10.1002/hep.26639. Epub 2013 Nov 22.
Although 20%-40% of persons with acute hepatitis C virus (HCV) infection demonstrate spontaneous clearance, the time course and factors associated with clearance remain poorly understood. We investigated the time to spontaneous clearance and predictors among participants with acute HCV using Cox proportional hazards analyses. Data for this analysis were drawn from an international collaboration of nine prospective cohorts evaluating outcomes after acute HCV infection. Among 632 participants with acute HCV, 35% were female, 82% were Caucasian, 49% had interleukin-28 (IL28)B CC genotype (rs12979860), 96% had injected drugs ever, 47% were infected with HCV genotype 1, and 7% had human immunodeficiency virus (HIV) coinfection. Twenty-eight percent were HCV antibody negative/RNA positive at the time of acute HCV detection (early acute HCV). During follow-up, spontaneous clearance occurred in 173 of 632, and at 1 year after infection, 25% (95% confidence interval [CI]: 21, 29) had cleared virus. Among those with clearance, the median time to clearance was 16.5 weeks (IQR: 10.5, 33.4), with 34%, 67%, and 83% demonstrating clearance at 3, 6, and 12 months. Adjusting for age, factors independently associated with time to spontaneous clearance included female sex (adjusted hazards ratio [AHR]: 2.16; 95% CI: 1.48, 3.18), IL28B CC genotype (versus CT/TT; AHR, 2.26; 95% CI: 1.52, 3.34), and HCV genotype 1 (versus non-genotype 1; AHR: 1.56; 95% CI: 1.06, 2.30). The effect of IL28B genotype and HCV genotype on spontaneous clearance was greater among females, compared to males.
Female sex, favorable IL28B genotype, and HCV genotype 1 are independent predictors of spontaneous clearance. Further research is required to elucidate the observed sex-based differences in HCV control.
尽管 20%-40%的急性丙型肝炎病毒 (HCV) 感染者可自发清除病毒,但人们对清除的时间过程和相关因素仍知之甚少。本研究采用 Cox 比例风险分析方法,对急性 HCV 感染者的自发清除时间和预测因素进行了研究。本分析的数据来自于一项国际性的 9 项前瞻性队列研究,评估了急性 HCV 感染后的结局。在 632 例急性 HCV 感染者中,35%为女性,82%为白种人,49%为白细胞介素 28(IL28)B 基因 CC 基因型(rs12979860),96%有过静脉吸毒史,47%感染 HCV 基因型 1,7%合并人类免疫缺陷病毒(HIV)感染。在急性 HCV 检测时,28%的患者为 HCV 抗体阴性/RNA 阳性(早期急性 HCV)。在随访期间,632 例患者中有 173 例自发清除了病毒,感染后 1 年时,25%(95%可信区间 [CI]:21,29)的患者清除了病毒。在清除病毒的患者中,中位清除时间为 16.5 周(IQR:10.5,33.4),34%、67%和 83%分别在 3、6 和 12 个月时清除了病毒。校正年龄后,与自发清除时间相关的独立因素包括女性(校正危险比 [AHR]:2.16;95%CI:1.48,3.18)、IL28B 基因 CC 基因型(与 CT/TT 相比;AHR:2.26;95%CI:1.52,3.34)和 HCV 基因型 1(与非基因型 1 相比;AHR:1.56;95%CI:1.06,2.30)。与男性相比,IL28B 基因型和 HCV 基因型对女性自发清除的影响更大。
女性、有利的 IL28B 基因型和 HCV 基因型 1 是自发清除的独立预测因素。需要进一步研究阐明 HCV 控制中观察到的基于性别的差异。