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

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Abstract
Background : A relationship between the pretreatment RNA titre of GB virus C/hepatitis G virus (GBV‐C/HGV) and the effectiveness of interferon (IFN) therapy has been reported previously. However, the influence of changes in the 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 explored in patients with chronic hepatitis caused by hepatitis C virus. We examined the relationship between changes in the amino‐acid sequence of the NS5A 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‐RNA (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 residues 1865–2279; NS5A1865–2279) of pretreatment GBV‐C/HGV‐RNA by direct sequencing. Results : The pretreatment GBV‐C/HGV‐RNA level of CR patients (7.8 × 104–6.2 × 105, mean 3.30 × 105) was significantly lower than that of NR patients (6.3 × 107–7.2 × 108, mean 3.55 × 108; P < 0.01). The number of amino acid substitutions in NS5A1865–2279 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 substitutions or sites of substitution in NS5A1865–2279 that were specific to either group. Conclusions : The effectiveness of IFN therapy for GBV‐C/HGV is strongly related to the pretreatment GBV‐C/HGV‐RNA level, but is not related to changes in NS5A1865–2279.

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