Variations in the viral NS5B region in Japanese patients with chronic hepatitis C virus genotype 1b infection. No specific amino acid substitution was identified as determinants of treatment response to interferon/ribavirin combination therapy.
OBJECTIVE
A recent study suggested that the substitution of amino acid 415 of HCV NS5B from phenylalanine to tyrosine in patients with HCV genotype 1a infection is induced by ribavirin and responsible for resistance to ribavirin therapy. The aim of this study was to evaluate whether specific variations in the HCV NS5B sequence in Japanese patients with HCV genotype 1b (HCV/1b) infection are associated with treatment response or selected by treatment with interferon-alpha/ribavirin combination therapy.


METHODS
Eighteen Japanese patients with HCV/1b infection receiving interferon-alpha/ribavirin combination therapy for 24 weeks were studied. Five patients treated with interferon-alpha monotherapy for 24 weeks were also studied as controls. The entire HCV NS5B sequence before and after therapy was determined.


RESULTS
All HCV isolates had tyrosine at position 415 of NS5B before and after therapy. Further analysis showed that no specific amino acid substitutions were identified to associate with clinical response and no specific amino acid substitutions were induced/selected by the clinical treatment.


CONCLUSIONS
No specific HCV NS5B nucleotide/amino acid sequence variations, including amino acid 415 of NS5B, were identified as being associated with clinical treatment response or selected by the combination therapy in Japanese patients with HCV/1b infection.
Sugihara
Kanji
K
Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, and Department of Gastroenterology, Nagoya Daini Red Cross Hospital, Japan.
Orito
Etsuro
E
Tanaka
Yasuhito
Y
Kato
Takanobu
T
Lau
Johnson Y N
JY
Ohno
Tomoyoshi
T
Hayashi
Katsuo
K
Ogino
Masataka
M
Hirashima
Noboru
N
Sakakibara
Kenji
K
Mizuno
Yoshiki
Y
Kato
Hideaki
H
Suzuki
Seiji
S
Ueda
Ryuzo
R
Mizokami
Masashi
M
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D024882:Drug Resistance, Viral / Q000235:genetics*; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D007372:Interferons / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D011110:Polymorphism, Genetic; D012254:Ribavirin / Q000494:pharmacology / Q000627:therapeutic use; D016415:Sequence Alignment; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D012324:RNA-Dependent RNA Polymerase
D000998:Antiviral Agents; D007372:Interferons; D012254:Ribavirin; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase