| Limited information is available on the prevalence of hepatitis C virus (HCV) in the general population in China. Genes related to antigen presentation pathway play a vital role during the infection of hepatitis C virus. Few studies have examined the relation between the genetic variants of these genes and the outcomes of HCV. Genes related to antigen presentation pathway play a vital role during the infection of hepatitis C virus. This study evaluated the effect of PEG alpha interferon for the treatment of chronic hepatitis C and its risk factors, and to establish the prediction model.In Part I,a community-based epidemiologic study was carried out in three counties in eastern China. The results of Part I was as following.A total of 149175 individuals were investigated in 60 communities among three counties in Jiangsu province, eastern China, among whom 1175 subjects (0.79%,95% confidence interval (CI)= 0.74%-0.83%) were HCV antibody (anti-HCV) positive. The prevalence was low in children (0.09%,95% CI= 0.04%-0.17%), but increased progressively from adolescents (0.20%,95% CI= 0.15%-0.28%) to adults age 21 years and older (0.15-1.64%). Women had a higher prevalence of HCV infection than men in most age strata. In a multilevel regression analysis, age, sex, education, occupation, blood transfusion (OR= 2.91,95% CI= 1.09-5.37), invasive testing (OR = 1.28,95% CI= 1.14-1.61), and dental therapy (OR= 2.27,95% CI= 1.41-3.42) were association with HCV infection.In conclusion, although the prevalence of HCV in this population was low, the total reservoir of infection is significant and calls for public health measures, such as health education to limit the magnitude of the problem.hi Part II, the current sutdy determined the genotypes of 34 tagging single-nucleotide polymorphisms (SNPs) from 9 candidate genes (HLA-DMA, HLA-DMB, HLA-DOA, HLA-DOB, TAP1, TAP2, LMP2, LMP7, and Tapasin) in a HCV high risk population (former paid-blood donors).The results indicated that HLA-DMA rs 1063478 and HLA-DOA rs2284191 were independent factors of HCV antibody (anti-HCV) status, while HLA-DOB rs7383287 and LMP2 rsl7587 were independent factors of infection chronicity. The HLA-DMA,HLA-DOA,HLA-DOB, and LMP2 loci were novel identified candidate regions that were related to HCV infection. The interaction analysis showed that exposure of plasma donation interacted with the combined effects of rs 1063478 and rs2284191 for HCV susceptibility, and the history of whole blood donation interacted with the association of rs7383287 with HCV clearance.In conclusion, our results suggested that genetic variants in antigen processing and presentation pathway had influence on HCV susceptibility and clearance.In Part III, this study is based on the patients with chronic hepatitis C in Jurong people’s hospital. Using prospective cohort follow-up study, all patients are treated by common alpha interferon for 48 weeks, after was followed up at 24 weeks to observe the rate of sustained vriological response (SVR). The current sutdy determined the genotypes of HLA-DOA rs2284191, HLA-DOB rs7383287, HLA-DMA rslO63478and IMP2 rs17587.The 336 cases completed the treatment therapeutic regimen and follow-up, and the SVR rate was 75.3%. There were significant differences in baseline viral load, gamma-glutamyl transpeptadase (GGT), glucose (GLU), triiodothyronine (T3), thyroxine (T4), platelet count and AFP between SVR and non-SVR groups. The results indicated that HLA-DMA rs1063478 (OR= 2.05,95%Cl= 1.24-3.41, P= 0.005) and LMP2 rs17587 (OR= 2.04,95% CI= 1.23-3.35, P= 0.005) were independent factors of SVR.In conclusion, HLA-DMA rs 1063478, LMP2 rs17587, the baseline, GLU, T4 and platelet count may be association with SVR of chronic hepatitis C. |
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