Association of amino acid substitution pattern in core protein of hepatitis C virus genotype 2a high viral load and virological response to interferon-ribavirin combination therapy.
BACKGROUND
Substitution of amino acids (aa) 70 and 91 in the core region of HCV genotype 1b is a useful pretreatment predictor of poor response to interferon + ribavirin combination therapy, but the impacts of aa substitutions in the core region of HCV genotype 2a are still not clear.


METHODS
154 consecutive Japanese adults with a high viral load (> or =100 kIU/ml) of genotype 2a who could complete combination therapy for 24 weeks were evaluated. To examine the differences in virological characteristics between non-sustained virological response (non-SVR) and rapid responder (SVR patients who could achieve a HCV-RNA-negative status within 8 weeks), 86 patients could be analyzed by pretreatment substitution patterns of the core region.


RESULTS
SVR was achieved in 127 of 154 patients (83%), and rapid response in 113 of 127 (90%). In all 154 patients, multivariate analysis identified younger age, lower level of viremia, and higher level of albumin as significant determinants of SVR. As significant determinants of rapid response in 86 patients, multivariate analysis identified substitution of aa 4 (non-asparagine) in addition to the significant determinants of SVR.


CONCLUSIONS
Our results suggest that the aa substitution pattern of the core region in patients with a high titer of genotype 2a may partly affect the virological response to combination therapy.
Akuta
Norio
N
Department of Hepatology, Toranomon Hospital, Tokyo 105-0001, Japan. akuta-gi@umin.ac.jp
Suzuki
Fumitaka
F
Hirakawa
Miharu
M
Kawamura
Yusuke
Y
Yatsuji
Hiromi
H
Sezaki
Hitomi
H
Suzuki
Yoshiyuki
Y
Hosaka
Tetsuya
T
Kobayashi
Masahiro
M
Kobayashi
Mariko
M
Saitoh
Satoshi
S
Arase
Yasuji
Y
Ikeda
Kenji
K
Kumada
Hiromitsu
H
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage*; D016896:Treatment Outcome; D014758:Viral Core Proteins / Q000235:genetics*; D019562:Viral Load / Q000187:drug effects*
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D012254:Ribavirin