博茨瓦纳肝病患者丙型肝炎病毒的分子特征：一项回顾性横断面研究。
Molecular characterization of hepatitis C virus in liver disease patients in Botswana: a retrospective cross-sectional study.
机构信息
Botswana Harvard AIDS Institute Partnership, Research Laboratory, Gaborone, Botswana.
Department of Applied Biology and Biochemistry, National University of Science and Technology, Bulawayo, Zimbabwe.
出版信息
BMC Infect Dis. 2019 Oct 22;19(1):875. doi: 10.1186/s12879-019-4514-1.
BACKGROUND
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease globally. Direct acting antivirals (DAAs) have proven effective in curing HCV. However, the current standard of care (SOC) in Botswana remains PEGylated interferon-α (IFN-α) with ribavirin. Several mutations have been reported to confer resistance to interferon-based treatments. Therefore, there is a need to determine HCV genotypes in Botswana, as these data will guide new treatment guidelines and understanding of HCV epidemiology in Botswana.
METHODS
This was a retrospective cross-sectional pilot study utilizing plasma obtained from 55 participants from Princess Marina Hospital in Gaborone, Botswana. The partial core region of HCV was amplified, and genotypes were determined using phylogenetic analysis.
RESULTS
Four genotype 5a and two genotype 4v sequences were identified. Two significant mutations - K10Q and R70Q - were observed in genotype 5a sequences and have been associated with increased risk of hepatocellular carcinoma (HCC), while R70Q confers resistance to interferon-based treatments.
CONCLUSION
Genotypes 5a and 4v are circulating in Botswana. The presence of mutations in genotype 5 suggests that some patients may not respond to IFN-based regimens. The information obtained in this study, in addition to the World health organization (WHO) recommendations, can be utilized by policy makers to implement DAAs as the new SOC for HCV treatment in Botswana.
背景
丙型肝炎病毒（HCV）感染是全球慢性肝病的主要原因。直接作用抗病毒药物（DAAs）已被证明可有效治愈 HCV。然而，博茨瓦纳目前的标准治疗方法（SOC）仍然是聚乙二醇干扰素-α（IFN-α）联合利巴韦林。已有报道称，几种突变可导致对基于干扰素的治疗产生耐药性。因此，有必要确定博茨瓦纳的 HCV 基因型，因为这些数据将指导新的治疗指南和对博茨瓦纳 HCV 流行病学的理解。
方法
这是一项回顾性横断面试点研究，利用来自博茨瓦纳哈博罗内 Princess Marina 医院的 55 名参与者的血浆进行。扩增 HCV 的部分核心区，并通过系统发育分析确定基因型。
结果
鉴定出 4 个基因型 5a 和 2 个基因型 4v 序列。在基因型 5a 序列中观察到 2 个重要突变 - K10Q 和 R70Q - ，它们与肝癌（HCC）风险增加有关，而 R70Q 可导致对基于干扰素的治疗产生耐药性。
结论
基因型 5a 和 4v 在博茨瓦纳流行。基因型 5 中的突变表明，一些患者可能无法对 IFN 方案产生反应。本研究获得的信息以及世界卫生组织（WHO）的建议可被决策者用来在博茨瓦纳实施 DAA 作为 HCV 治疗的新 SOC。
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