Influence of RNA titre and amino acid changes in the NS5A region of GB virus C hepatitis G virus on the effectiveness of interferon therapy

Background: A relationship between the pretreatment RNA titre of GB virus C /hepatitis G virus (GBV-C/HGV) and the effectiveness of interferon (IFN) th erapy has been reported previously. However, the influence of changes in th e amino acid sequence of the NS5A region of GBV-C/HGV on the effectiveness of IFN therapy has not been examined, although this influence has been expl ored in patients with chronic hepatitis caused by hepatitis C virus. We exa mined the relationship between changes in the amino-acid sequence of the NS 5A region and the effectiveness of IFN therapy. Methods: The subjects were 10 patients with chronic hepatitis C coinfected with GBV-C/HGV and treated with IFN. The pretreatment level of GBV-C/HGV-RN A (copies/mL) in their sera was measured by real-time detection polymerase chain reaction (PCR) assay. At 6 months after cessation of therapy, four of 10 patients had become negative for GBV-C/HGV-RNA (CR, complete response) and six patients were still positive for GBV-C/HGV-RNA (NR, non-response). We determined the nucleotide sequence of the NS5A region (amino acid residu es 1865-2279; NS5A(1865-2279)) of pretreatment GBV-C/HGV-RNA by direct sequ encing. Results: The pretreatment GBV-C/HGV-RNA level of CR patients (7.8 x 10(4)-6 .2 x 10(5), mean 3.30 x 10(5)) was significantly lower than that of NR pati ents (6.3 x 10(7)-7.2 x 10(8), mean 3.55 x 10(8); P < 0.01). The number of amino acid substitutions in NS5A(1865-2279) was five to seven (mean 5.8 +/- 1.0) in CR patients, and four to eight (mean 6.8 +/- 1.6) in NR patients, a difference that is not significant. Moreover, there were no amino acid su bstitutions or sites of substitution in NS5A(1865-2279) that were specific to either group. Conclusions: The effectiveness of IFN therapy for GBV-C/HGV is strongly rel ated to the pretreatment GBV-C/HGV-RNA level, but is not related to changes in NS5A(1865-2279). (C) 2000 Blackwell Science Asia Pty Ltd.