A study was undertaken to explore the molecular mechanisms underlying control of HCV infection in blood donors in China. Factors including clinical information, anti-HCV reactivity (S/CO), IFN-alpha and IFN-gamma, viral loads and genotypes were correlated with 160 index plasma samples at three statuses of 45 recovered, 76 chronic or 39 false positive anti-HCV reactive blood donors. The spontaneous recovery rate was 37.2%. Viral loads of 76 HCV plasmas ranged between 59.8 IU/ml and 2.43 x 10(6) IU/ml (median 3.67 x 10(4) IU/ml). Genotypes 1, 2, 3 and 6 of 63 HCV strains were identified phylogenetically. Recovered donors were significantly younger (p = 0.002) and had lower level IFN-gamma (p = 0.001) than chronically HCV infected donors. Circulating levels of IFN-alpha and IFN-gamma were higher in those with low viral load and were low in middle or high viral load samples. The ratio of IFN-alpha to IFN-gamma (IFN-alpha/gamma) was significantly positively correlated with viral load (p = 0.037), and viral load was inversely correlated with IFN-gamma in chronic HCV infection regardless of genotype. The study revealed clearly different relationships between IFN-alpha and IFN-gamma in relation to viral load in HCV. A novel measure of IFN-alpha/gamma ratio could be a new approach to evaluate long term outcome of HCV infection. (C) 2011 Elsevier Inc. All rights reserved.