Abstract：
Factor VIII and IX clotting factor concentrates manufactured from pooled plasma have been identified as potent sources of virus infection in persons with hemophilia (PWHs) in the 1970s and 1980s. To investigate the range and diversity of viruses over this period, we analysed 24 clotting factor concentrates for several blood-borne viruses. Nucleic acid was extracted from 14 commercially produced clotting factors and 10 from nonremunerated donors, preserved in lyophilized form (expiry dates: 1974-1992). Clotting factors were tested by commercial and in-house quantitative PCRs for blood-borne viruses hepatitis A, B, C and E viruses (HAV, HBV, HCV, HEV), HIV- types 1/2, parvoviruses B19V and PARV4, and human pegiviruses types 1 and 2 (HPgV-1,-2). HCV and HPgV-1 were the most frequently detected viruses (both 14/24 tested) primarily in commercial clotting factors, with frequently extremely high viral loads in the late 1970s-1985 and a diverse range of HCV genotypes. Detection frequencies sharply declined following introduction of virus inactivation. HIV-1, HBV, and HAV were less frequently detected (3/24, 1/24, and 1/24 respectively); none were positive for HEV. Contrastingly, B19V and PARV4 were detected throughout the study period, even after introduction of dry heat treatment, consistent with ongoing documented transmission to PWHs into the early 1990s. While hemophilia treatment is now largely based on recombinant factor VIII/IX in the UK and elsewhere, the comprehensive screen of historical plasma-derived clotting factors reveals extensive exposure of PWHs to blood-borne viruses throughout 1970s-early 1990s, and the epidemiological and manufacturing parameters that influenced clotting factor contamination.
摘要：
从汇集的血浆制造的因子VIII和IX凝血因子浓缩物在1970年代和1980年代已被鉴定为血友病(PWHs)患者的有效病毒感染源。为了调查这一时期病毒的范围和多样性，我们分析了24种血液传播病毒的凝血因子浓缩物。核酸是从14种商业生产的凝血因子和10种无偿捐献者中提取的，以冻干形式保存（有效期：1974-1992年）。凝血因子通过商业和内部定量PCR检测血源性病毒甲型肝炎，B,C和E病毒（HAV，HBV,HCV,HEV),HIV-1/2型，细小病毒B19V和PARV4，以及人类pegivirus1和2型（HPgV-1，-2）。HCV和HPgV-1是最常见的检测病毒（14/24测试）主要在商业凝血因子，在1970年代末-1985年，病毒载量经常极高，HCV基因型范围也各不相同。引入病毒灭活后，检测频率急剧下降。HIV-1,HBV,和HAV的检出频率较低（分别为3/24、1/24和1/24）；无HEV阳性。相反，在整个研究期间检测到B19V和PARV4，即使在引入干热处理后，与20世纪90年代初正在进行的有据可查的传输到PWHs是一致的。虽然在英国和其他地方，血友病治疗现在主要基于重组因子VIII/IX，对历史血浆来源的凝血因子的全面筛选表明，在整个1970年代至1990年代初，PWHs广泛暴露于血液传播病毒，以及影响凝血因子污染的流行病学和制造参数。
