Kedda M A, Kew M C, Cohn R J, Field S P, Schwyzer R, Song E, Fernandes-Costa F
Medical Research Council/Witwatersrand University Molecular Hepatology Research Unit, Johannesburg, South Africa.
Hepatology. 1995 Nov;22(5):1363-7.
We report an outbreak of hepatitis A in nine South African hemophiliacs treated exclusively with infusions of factor VIII concentrate. The solvent/detergent (S/D) method (which does not inactivate nonenveloped viruses) was used for virus eradication. In three of six patients studied at a molecular level hepatitis A virus (HAV) complementary DNA (cDNA) amplified from serum by reverse transcription-polymerase chain reaction (RT-PCR) was identical to HAV cDNA in 1 of 14 lots (no. 53) of factor VIII tested. The plasma for lot 53 was obtained from donors in the United States: 1 of 12 samples of this source material contained the same HAV cDNA sequences. In another two patients receiving lot 53, the degree of identity between HAV cDNA in serum and that in factor VIII was only 88% and 89%, respectively, and in the sixth patient, who did not receive lot 53, it was 90%. The degree of HAV cDNA homology among five patients in an independent point-source outbreak of hepatitis A was 100%, and that in nine patients who acquired this infection sporadically in Johannesburg, Egypt, or Russia, was 93% to 100%. Whether the three hemophiliacs with low HAV cDNA homology with lot 53 acquired the infection from other unidentified virus strains contaminating factor VIII or from extraneous sources is unknown. This study provides further evidence that factor VIII concentrate prepared by the S/D method may be contaminated by the HAV, in this instance at source, and may cause hepatitis in recipients. Proof of a cause-and-effect relationship will, however, depend on animal inoculation studies.
我们报告了一起甲型肝炎疫情，涉及9名仅接受过凝血因子VIII浓缩物输注治疗的南非血友病患者。采用了溶剂/去污剂（S/D）法（该方法不能使无包膜病毒失活）来消除病毒。在6名接受分子水平研究的患者中，有3名患者血清中通过逆转录-聚合酶链反应（RT-PCR）扩增出的甲型肝炎病毒（HAV）互补DNA（cDNA）与所检测的14批凝血因子VIII中的1批（第53批）的HAV cDNA相同。第53批血浆来自美国的献血者：该原料的12份样本中有1份含有相同的HAV cDNA序列。在另外两名接受第53批产品的患者中，血清中的HAV cDNA与凝血因子VIII中的HAV cDNA的同源性分别仅为88%和89%，而在未接受第53批产品的第6名患者中，同源性为90%。在一次独立的甲型肝炎点源暴发中，5名患者的HAV cDNA同源性为100%，而在约翰内斯堡、埃及或俄罗斯零星感染该病毒的9名患者中，同源性为93%至100%。这3名与第53批产品HAV cDNA同源性较低的血友病患者是从污染凝血因子VIII的其他未鉴定病毒株感染，还是从外部来源感染，尚不清楚。本研究进一步证明，采用S/D法制备的凝血因子VIII浓缩物可能被HAV污染，在本案例中是源头污染，可能导致接受者感染肝炎。然而，因果关系的证明将取决于动物接种研究。
