Beld M, Penning M, van Putten M, Lukashov V, van den Hoek A, McMorrow M, Goudsmit J
Department of Human Retrovirology, Academic Medical Centre, Amsterdam, the Netherlands.
Hepatology. 1999 Apr;29(4):1288-98. doi: 10.1002/hep.510290442.
To gain insight into the natural history of hepatitis C virus (HCV), 13 human immunodeficiency virus (HIV)-seronegative injecting drug users were studied who seroconverted for HCV as determined by third-generation enzyme-linked immunosorbent assay, showed an ensuing antibody response to HCV, and were not treated with any antiviral drugs during follow-up. Subjects included 13 untreated HIV-negative individuals, of whom 5 (38.5%) apparently cleared HCV and were polymerase chain reaction (PCR)-negative in at least 3 consecutive samples, 3 (23.1%) showed transient viremia and were PCR-negative in 1 sample during the study period, and the other 5 (38.5%) showed persistent viremia. Viremia was determined longitudinally by reverse-transcription PCR (RT-PCR) and quantified by branched DNA (bDNA). HCV genotypes were determined on serial samples during follow-up. Quantitative antibody levels to core, NS3, NS4, and NS5 were determined using the Chiron RIBA HCV-titering Strip Immunoblot Assay, which is based on HCV genotype 1. The antibody responses to core, NS3, NS4, and NS5 were erratic. In individuals infected with HCV genotype 1, significantly higher median antibody responses to core (P =.02) and to NS4 (P =.04) were found as compared with those infected with other genotypes, showing a significant impact of HCV genotype specificity of the assay. In groups infected with HCV genotype 1, significantly higher median NS3 antibody titers (2.61 relative intensity [RI] vs. 0.38 RI; P =.003) were found in the individuals with persistent viremia than in those with apparent resolution of HCV RNA in blood. In groups infected with genotypes other than genotype 1, significantly higher median NS3 antibody titers (0.89 RI vs. 0.03 RI; P =.0004) and NS5 antibody titers (1.86 RI vs. 0.01 RI; P =.006) were found in the individuals with persistent viremia than in those with apparent resolution of HCV RNA in blood. Individuals with viral persistence had higher HCV-RNA loads with higher antibody responses as compared with individuals with apparent viral clearance from blood. Apparent viral clearance from blood was observed in an unexpectedly high percentage (38.5%), associated with a significant decrease of antibodies to NS3, independent of HCV genotype, as compared with individuals with persistent viremia (P <.005). Apparent viral clearance from blood with gradual loss of antibodies to various HCV proteins, independent of HCV genotype, was observed in 4 of the 5 individuals within approximately 1 year after HCV seroconversion, whereas 1 of these individuals apparently cleared the virus from blood, with complete seroreversion.
为深入了解丙型肝炎病毒（HCV）的自然史，我们对13名人类免疫缺陷病毒（HIV）血清学阴性的注射吸毒者进行了研究。这些人经第三代酶联免疫吸附试验检测出HCV血清转化，随后出现针对HCV的抗体反应，且在随访期间未接受任何抗病毒药物治疗。研究对象包括13名未接受治疗的HIV阴性个体，其中5人（38.5%）显然清除了HCV，至少连续3份样本的聚合酶链反应（PCR）检测呈阴性；3人（23.1%）出现短暂病毒血症，在研究期间1份样本的PCR检测呈阴性；另外5人（38.5%）表现为持续性病毒血症。通过逆转录PCR（RT-PCR）纵向检测病毒血症，并采用分支DNA（bDNA）进行定量分析。在随访期间对系列样本进行HCV基因型测定。使用基于HCV 1型的Chiron RIBA HCV滴定条免疫印迹法测定针对核心蛋白、NS3、NS4和NS5的定量抗体水平。针对核心蛋白、NS3、NS4和NS5的抗体反应不稳定。与感染其他基因型的个体相比，感染HCV 1型的个体对核心蛋白（P = 0.02）和NS4（P = 0.04）的抗体反应中位数显著更高，表明该检测方法的HCV基因型特异性具有显著影响。在感染HCV 1型的组中，持续性病毒血症个体的NS3抗体滴度中位数（相对强度[RI]为2.61，而病毒血症明显消退个体为0.38 RI；P = 0.003）显著高于血液中HCV RNA明显消退的个体。在感染非1型基因型的组中，持续性病毒血症个体的NS3抗体滴度中位数（0.89 RI对0.03 RI；P = 0.0004）和NS5抗体滴度中位数（1.86 RI对0.01 RI；P = 0.006）显著高于血液中HCV RNA明显消退的个体。与血液中病毒明显清除的个体相比，病毒持续存在的个体具有更高的HCV - RNA载量和更高的抗体反应。血液中病毒明显清除的比例出人意料地高（38.5%），与持续性病毒血症个体相比，无论HCV基因型如何，其针对NS3的抗体显著降低（P < 0.005）。在HCV血清转化后约1年内，5名个体中有4名出现血液中病毒明显清除，同时针对各种HCV蛋白的抗体逐渐减少，且与HCV基因型无关，其中1名个体血液中病毒明显清除，血清完全逆转。
