Beld M, Penning M, van Putten M, van den Hoek A, Damen M, Klein M R, Goudsmit J
Academic Medical Centre, University of Amsterdam, Department of Human Retrovirology, Amsterdam, The Netherlands.
Blood. 1999 Aug 15;94(4):1183-91.
Screening of antibodies to hepatitis C virus (HCV) is widely used for monitoring the prevalence of HCV infections and to assess HCV infectivity. Among HCV-infected individuals in the general population, the interval between the detection of HCV RNA and the development of HCV antibodies is usually 5 to 6 weeks, but in rare cases, seroconversion may be prolonged up to 6 to 9 months. In this study, we tested for the presence of HCV RNA during the antibody-undetectable period of 19 drug-injecting HCV seroconverters to gain insight into the antibody-negative carrier status in this population. HCV seroconversion status was determined by testing the first and last serum samples obtained from each subject, using third-generation antibody screening and confirmation assays. Serial samples were tested for HCV-specific antibodies to establish the moment of seroconversion and HCV RNA by single reverse transcriptase-polymerase chain reaction (RT-PCR) and branched DNA assay (bDNA) in serum. Plasma and peripheral blood mononuclear cells (PBMCs) were independently collected and tested for HCV RNA. HCV RNA-positivity was confirmed by Southern blot hybridization and sequencing of serial samples. The 19 HCV seroconverters had a mean follow-up of 5 years (range, 1 to 8 years). Of the 19, 4 were human immunodeficiency virus (HIV)-infected before HCV seroconversion. HCV RNA was detected in serum before seroconversion in 12 (63.2%) of the 19 HCV seroconverters, independent of HIV status. In 7 of these 12, the antibody-undetectable period was relatively short (2 to 10 months). The other 5, who were all HIV-negative before HCV seroconversion, had intermittent low levels of HCV RNA before seroconversion for a period of more than 12 months, with a mean of 40.8 months (range, 13 to 94 months). In all 5 individuals, independent repeats of the experiments confirmed the presence of HCV RNA in serum, and in 3 of these individuals, HCV-positivity was confirmed in independently collected plasma and PBMC samples. Low levels of HCV RNA may be present during prolonged antibody-undetectable periods before seroconversion in a number of injecting drug users. Independent of HIV status, their immune system appears to be unable to respond to these low HCV RNA levels and was sometimes only activated after reinfections with distinct HCV genotypes. These results indicate that primary HCV infection may not always elicit the rapid emergence of HCV antibodies and suggests that persistent low levels of HCV RNA (regardless of the genotype) may not elicit at all or delay antibody responses for prolonged periods of time.
丙型肝炎病毒（HCV）抗体筛查被广泛用于监测HCV感染的流行情况并评估HCV传染性。在普通人群中，HCV感染者体内HCV RNA检测与HCV抗体产生之间的间隔通常为5至6周，但在少数情况下，血清转化可能会延长至6至9个月。在本研究中，我们对19名注射毒品的HCV血清转化者在抗体检测不到的时期进行了HCV RNA检测，以深入了解该人群中的抗体阴性携带者状态。通过检测从每个受试者获得的首份和末份血清样本，使用第三代抗体筛查和确认试验来确定HCV血清转化状态。对系列样本进行HCV特异性抗体检测以确定血清转化时刻，并通过血清中的单逆转录聚合酶链反应（RT-PCR）和分支DNA测定法（bDNA）检测HCV RNA。独立收集血浆和外周血单核细胞（PBMC）并检测其中的HCV RNA。通过Southern印迹杂交和系列样本测序确认HCV RNA阳性。这19名HCV血清转化者的平均随访时间为5年（范围1至8年）。在这19人中，有4人在HCV血清转化前感染了人类免疫缺陷病毒（HIV）。在19名HCV血清转化者中，有12人（63.2%）在血清转化前血清中检测到HCV RNA，与HIV状态无关。在这12人中，有7人的抗体检测不到期相对较短（2至10个月）。另外5人在HCV血清转化前均为HIV阴性，在血清转化前有超过12个月的时间间歇性出现低水平HCV RNA，平均为40.8个月（范围13至94个月）。在所有5名个体中，实验的独立重复均证实血清中存在HCV RNA，其中3名个体在独立收集的血浆和PBMC样本中也证实了HCV阳性。在一些注射毒品使用者血清转化前的长时间抗体检测不到期内，可能存在低水平的HCV RNA。与HIV状态无关，他们的免疫系统似乎无法对这些低水平的HCV RNA产生反应，有时只有在再次感染不同HCV基因型后才被激活。这些结果表明，原发性HCV感染可能并不总是会迅速产生HCV抗体，提示持续低水平的HCV RNA（无论基因型如何）可能根本不会引发或会长时间延迟抗体反应。
