Prediction of response to pegylated interferon and ribavirin in hepatitis C by polymorphisms in the viral core protein and very early dynamics of viremia.
OBJECTIVE
To evaluate power of amino acid polymorphisms in core protein of hepatitis C virus (HCV) for predicting sustained virological response (SVR) to pegylated interferon (Peg-IFN)/ribavirin, when they were combined with virological response.


METHODS
Peg-IFN/ribavirin was given to 118 patients infected with HCV genotype 1b in high viral loads. Amino acid polymorphisms (Arg70 vs. Gln70 and Leu91 vs. Met91) in combination with on-treatment virological responses were correlated with SVR.


RESULTS
End-of-treatment response (ETR) was achieved in 71% and SVR in 47% of the 118 patients. In multivariate analysis, Arg70 and Leu91, and higher ribavirin dose were independently associated with ETR. In patients with Gln70 and/or Met91, SVR was more frequent in those with than without prompt virological response (PVR) for a decrease in viral load >or=1.0 log by 48 h. Specificity in predicting patients without ETR and SVR, in combination with core polymorphisms, was not different between PVR and early virological response at 12 weeks.


CONCLUSIONS
Core polymorphisms combined with PVR would be useful in promptly identifying the patients who will not respond to Peg-IFN/ribavirin, thereby avoiding unrewarding side effects and high costs.
Akuta
Norio
N
Department of Hepatology, Toranomon Hospital, Tokyo, Japan. akuta-gi@umin.ac.jp
Suzuki
Fumitaka
F
Kawamura
Yusuke
Y
Yatsuji
Hiromi
H
Sezaki
Hitomi
H
Suzuki
Yoshiyuki
Y
Hosaka
Tetsuya
T
Kobayashi
Masahiro
M
Kobayashi
Mariko
M
Arase
Yasuji
Y
Ikeda
Kenji
K
Miyakawa
Yuzo
Y
Kumada
Hiromitsu
H
D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011092:Polyethylene Glycols; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D014758:Viral Core Proteins / Q000235:genetics*; D019562:Viral Load; D014766:Viremia
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b