Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
The Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
PLoS One. 2019 Mar 13;14(3):e0212734. doi: 10.1371/journal.pone.0212734. eCollection 2019.
The highest burden of disease from hepatitis C virus (HCV) is found in Southeast Asia, but our understanding of the epidemiology of infection in many heavily burdened countries is still limited. In particular, there is relatively little data on acute HCV infection, the outcome of which can be influenced by both viral and host genetics which differ within the region. We studied HCV genotype and IL28B gene polymorphism in a cohort of acute HCV-infected patients in Southern Vietnam alongside two other cohorts of chronic HCV-infected patients to better understand the epidemiology of HCV infection locally and inform the development of programs for therapy with the increasing availability of directly acting antiviral therapy (DAAs).
We analysed plasma samples from patients with acute and chronic HCV infection, including chronic HCV mono-infection and chronic Human Immunodeficiency Virus (HIV)-HCV coinfection, who enrolled in four epidemiological or clinical research studies. HCV infection was confirmed with RNA testing. The 5' UTR, core and NSB5 regions of HCV RNA positive samples were sequenced, and the genotype and subtype of the viral strains were determined. Host DNA from all HCV positive patients and age- and sex-matched non-HCV-infected control individuals were analysed for IL28B single nucleotide polymorphism (SNP) (rs12979860 and rs8099917). Geolocation of the patients were mapped using QGIS.
355 HCV antibody positive patients were analysed; 54.6% (194/355) and 46.4% (161/355) were acute and chronic infections, respectively. 50.4% (81/161) and 49.6.4% (80/161) of chronic infections had HCV mono-infection and HIV-HCV coinfection, respectively. 88.7% (315/355) and 10.1% (36/355) of the patients were from southern and central regions of Vietnam, respectively. 92.4% (328/355) of patients were HCV RNA positive, including 86.1% (167/194) acute and 100% (161/161) chronic infections. Genotype could be determined in 98.4% (322/328) patients. Genotypes 1 (56.5%; 182/322) and 6 (33.9%; 109/322) predominated. Genotype 1 including genotype 1a was significantly higher in HIV-HCV coinfected patients compared to acute HCV patients [43.8% (35/80) versus 20.5% (33/167)], (p = <0.001), while genotype 6 was significantly higher in chronic HCV mono-infected patients [(44.4% (36/81) versus 20.0% (16/80)] (p = < 0.004) compared to HIV-HCV coinfected patients. The prevalence of IL28B SNP (rs12979860) homozygous CC was 86.46% (83/96) in control individuals and was significantly higher in acutely-infected compared to chronically-infected patients [93.2 (82/88) versus 76.1% (35/46)] (p = < 0.005).
HCV genotype 6 is highly prevalent in Vietnam and the high prevalence in treatment naïve chronic HCV patients may results from poor spontaneous clearance of acute HCV infection with genotype 6.
丙型肝炎病毒（HCV）造成的疾病负担最高的地区是东南亚，但我们对许多负担沉重的国家的感染流行病学仍了解有限。特别是，有关急性 HCV 感染的数据相对较少，其结果可能受到病毒和宿主遗传因素的影响，而这些因素在该地区存在差异。我们研究了越南南部急性 HCV 感染患者队列以及另外两个慢性 HCV 感染患者队列中的 HCV 基因型和 IL28B 基因多态性，以便更好地了解当地 HCV 感染的流行病学，并为越来越多的直接作用抗病毒治疗（DAA）的治疗方案的制定提供信息。
我们分析了来自四个流行病学或临床研究的急性和慢性 HCV 感染患者（包括慢性 HCV 单感染和慢性人类免疫缺陷病毒（HIV）-HCV 合并感染）的血浆样本。使用 RNA 检测确认 HCV 感染。对 HCV RNA 阳性样本的 5'UTR、核心和 NSB5 区域进行测序，确定病毒株的基因型和亚型。对所有 HCV 阳性患者和年龄及性别匹配的非 HCV 感染对照个体的宿主 DNA 进行 IL28B 单核苷酸多态性（SNP）（rs12979860 和 rs8099917）分析。使用 QGIS 对患者的地理位置进行映射。
共分析了 355 例 HCV 抗体阳性患者；54.6%（194/355）和 46.4%（161/355）分别为急性和慢性感染。慢性感染中有 50.4%（81/161）和 49.6.4%（80/161）分别为 HCV 单感染和 HIV-HCV 合并感染。355 例患者中，88.7%（315/355）和 10.1%（36/355）分别来自越南南部和中部地区。92.4%（328/355）的患者 HCV RNA 阳性，包括 86.1%（167/194）的急性感染和 100%（161/161）的慢性感染。98.4%（322/328）的患者可以确定基因型。基因型 1（56.5%；182/322）和 6（33.9%；109/322）为主。HIV-HCV 合并感染患者中基因型 1 包括基因型 1a 的比例明显高于急性 HCV 患者[43.8%（35/80）比 20.5%（33/167）]（p<0.001），而慢性 HCV 单感染患者中基因型 6 的比例明显高于 HIV-HCV 合并感染患者[44.4%（36/81）比 20.0%（16/80）]（p<0.004）。在对照个体中，IL28B SNP（rs12979860）纯合 CC 的患病率为 86.46%（83/96），在急性感染患者中明显高于慢性感染患者[93.2%（82/88）比 76.1%（35/46）]（p<0.005）。
HCV 基因型 6 在越南高度流行，在未经治疗的慢性 HCV 患者中高患病率可能是由于基因型 6 的急性 HCV 感染自发清除率低所致。
