Relationship between the effect of interferon therapy and the change of hepatitis C virus non-structural 5B gene.
BACKGROUND
Hepatitis C virus (HCV)-RNA titre has been regarded as a factor affecting the response to interferon (IFN) therapy of patients with chronic hepatitis C (CHC). The focus of our study is the investigation of the nucleotide sequence of HCV-RNA NS5B, which may code RNA-dependent RNA polymerase and NS5A in the sera of 33 patients with CHC prior to IFN therapy.


METHODS
Hepatitis C virus genotype and HCV-RNA titre were examined by polymerase chain reaction (PCR) and competitive reverse transcriptase-PCR.


RESULTS
The sequence for HCV-RNA NS5B (nt 8331-8600 in 1b and 8410-8679 in 2a) was determined by direct sequencing. The changes of the predicted amino acids in the genotype-specific sites of HCV-J, HCV-BK, HC-J4/83, HCV-JT, HCV-N, HC-J6 and HCV-K2a were examined, and the mutation was defined when changes of amino acids in sites specific to different reported genotypes were revealed. The mutations were observed in 6/19 (32%) in genotype 1b and 9/14 (64%) in 2a. In the 1b group, complete response (CR) was achieved in 5/6 of the mutant and in 2/13 of the wild type groups (P < 0.05). No relationship was observed between IFN effectiveness and HCV-RNA titre in the 1b wild type group. In the 2a group, CR was achieved in 4/9 of the mutant and in 4/5 of the wild type groups. An inverse relationship between IFN responsiveness and HCV-RNA titre was apparent in 1b mutant, 2a wild and 2a mutant.


CONCLUSIONS
These data suggest the possible relationship between changes in the HCV-NS5B gene and the effect of IFN therapy in CHC patients with genotype 1b.
Horiike
N
N
Third Department of Internal Medicine, Ehime University School of Medicine, Japan. horiike@m.ehime-u.ac.jp
Michitaka
K
K
Masumoto
T
T
Okura
I
I
Akbar
S M
SM
Onji
M
M
D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000627:therapeutic use*; D001483:Base Sequence; D005260:Female; D005814:Genes, Viral / Q000235:genetics*; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000628:therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins