Lymphotropic hepatitis C virus has an interferon-resistant phenotype

Hepatitis C virus (HCV) infects and associates with B cells, leading to abnormal B-cell activation and development of lymphoproliferative and autoimmune disorders. This immune perturbation may in turn be associated with the resistance of HCV against the host immune system. The objective of this study was to analyse the effects of HCV infection of B cells on the efficacy of interferon (IFN)-based therapy. The study enrolled 102 patients with chronic hepatitis C who were treated with pegylated IFN plus ribavirin. HCV RNA titres in B cells were compared in patients with rapid viral responder (RVR) vs non-RVR, sustained viral responder (SVR) vs non-SVR and null viral responder (NVR) vs VR. The levels of HCV RNA in B cells were significantly higher in non-RVR, non-SVR and NVR groups. Association between the therapy outcome and the positive B-cell HCV RNA was also investigated in relation to other known viral and host factors. Multivariable analyses showed that the positive B-cell HCV RNA and the minor single-nucleotide polymorphism near the IL28B gene (rs8099917) were independent factors associated with NVR in patients infected with HCV genotype 1. When these two factors were combined, the sensitivity, specificity, positive and negative predictive values for NVR were 92.3%, 98.2%, 92.3% and 98.2%, respectively. Genotype 1 and the presence of one or no mutations in the IFN-sensitivity determining region were associated with higher levels of B-cell HCV RNA. B-cell-tropic HCV appears to have an IFN-resistant phenotype. B-cell HCV RNA positivity is a predictive factor for resistance to IFN-based therapy.