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) 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 GBVC/HGV-RNA by direct sequencing.


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 patients (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 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.
The Third Department of Internal Medicine, Ehime University School of Medicine, Japan.
T
T
Fujisawa
N
N
Horiike
K
K
Michitaka
M
M
Onji
D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D005260:Female; D018067:Flaviviridae / Q000235:genetics* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy; D006525:Hepatitis, Viral, Human / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000032:analysis*; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome; D017361:Viral Nonstructural Proteins / Q000235:genetics*
D016898:Interferon-alpha; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins