| Hepatitis C virus (HCV) belongs to the family Flaviviridae. Blood transfusion is one of the major routes for HCV infection. This project investigated how to reduce the risk of HCV infection in blood transfusion, and was separated as two parts, the "healthy" blood donors or found HCV infected donors.1. Use of the HCV antibody detection test has significantly improved the quality and safety of blood transfusion in Chinese hospitals, and reduced HCV infection rate in blood transfusion from 53.26% to 13%. However, the HCV antibody detection does not secure the first 6 weeks of HCV infection the so called "window phase", in which the antibody response against HCV is negative. Blood transfusion without detection of HCV viral markers in the window period caused HCV infection. Therefore, the essential step to achieve HCV-free blood transfusion is to close the "window" by detecting HCV viral markers such as HCV RNA and HCV core antigen, in addition to the HCV antibody test.We then conducted a study for a total of 8649 serum samples taken from 8649 employer-organized voluntary blood donors. These samples were collected from the first-time blood donors in the municipal blood centers in Beijing, Shenzhen and Chengdu. These blood centers geographically represent the north, south and west of China, respectively. Out of the total of 8649 healthy blood donors,7 of them was found to be positive for the primary HCV viral markers, shown a 0.08%(7/8649) HCV infection in the blood donor cohort who had shown negative results for HCV antibody response. These 7 samples demonstrated positive readings for both HCV RNA and HCV core antigen. Their HCV infection was confirmed 3 months later with antibody detection. Among these 7 patients,3 were from the Beijing Blood Center (3/6190,0.05%),3 from the Shenzhen Blood Center (3/1693,0.18%) and 1 from the Chengdu Blood Center (1/766,0.13%). The HCV RNA results were consistent with that from the HCV antigen tests in all of the 7 patients. HCV genotype analysis reveals that 3 out of the 7 subjects were identified as HCV lb subtype infection.It appears that in China the HCV infection rate in the HCV seronegative blood donors between 18 and 60 years of age is around 0.081%, higher than that of 0.041% reported in western countries. To the best of our knowledge, this is the first report describing the residual risk of HCV transmission in the seronegative blood donors in China. Considering the large population of blood donors in China, the risk of HCV transmission via blood transfusion is still significant, although HCV antibody test has been used. Therefore, to reduce the residual risk of HCV infection post-transfusion, we strongly suggest to test HCV RNA or/and HCV core antigen as an essential screening for the blood donors who are negative for HCV antibody.2. In the second part of the work, we investigated the HCV clinical virology in the HCV infected blood donors. Serum samples from 491 otherwise healthy blood donors (M/F,297/194) were taken at the Langfang Blood Center. These samples were collected for this study because the anti-HCV antibody of these subjects was detectable in the blood screening test. Also, as this was their first time to be found positive for HCV infection, HCV proliferation in these individuals were not interfered with any antiviral drugs.HCV genotyping was done for these 491 blood donors first. Of these subjects,33 were found to be infected with genotype 1a (6.7%),204 with 1b (41.5%),177 with 2a (36.0%),33 with 2b (6.7%),13 with 3a (2.6%),9 with 3b (1.8%),12 with 6 (2.4%) and 10 with unidentified genotype (2.0%). The predominant HCV genotypes in this China cohort are 1b and 2a, resulting in 77.6% of HCV infection. We then measured the viral load in the serum samples in an attempt to learn the correlation between HCV genotype and viral replication in these individuals. Among the study genotypes the highest viral load was seen in the genotype 2a group, which was over 100-fold (2.31ogs) higher than that of lb (p<0.01), although both were the predominant genotypes in this cohort. The other genotypes had an average viral load below that of genotype 1b. As all of the study individuals were never being treated with antiviral agents, it implicates that although HCV genotype lb and 2a have almost identical infectivity in northern China, genotype 2a appears to have a priority to proliferate in a natural course of HCV infection.We next examined the HCV-specific antibody response in these genotype groups, in hoping to find the explanation of why genotype 2a amplifies more than others. As all of the individuals were positive for HCV antibody, the analysis was focused on the antibody response against major HCV epitope antigens of Core, NS3, NS4 and NS5, respectively. The genotype groups had their antibody positivity rate between 80-97%for NS3,84-91%for Core,10-51% for NS4 and 10-48% for NS5. The overall ranking for the antibody positivity to the epitopes followed the order of NS3 (95%)> Core (89%)> NS4 (47%)> NS5 (36%). This order appears to apply to all genotypes. The results suggest that antibodies to NS3 and Core appear to be the early biomarkers in HCV infection. As individuals infected with different HCV genotypes exhibited a similar pattern of antibody response against the four HCV epitopes, HCV genotypes appear to have no correlation with the epitope-specific antibody responses. Thus, antibody response in HCV infection does not account for the replication priority of genotype 2a. Intrinsic factors in genotype 2a infection might play an important role after HCV entering into the host cells. It appears that the host hepatocyte environment, at least in these Chinese subjects, was more supportive for genotype 2a rather than for genotype lb or other HCV genotypes. Accordingly, we found that the GPT (glutamate-pyruvate transaminase) level in the group infected with genotype 2a was higher than that with genotype lb (p<0.001,80±16vs67±8).Part of the results has been published in the Biomedicine & Pharmacotherapy (2009). Other manuscripts are in submission process. |
PDF Full Text Request