Predictive values of amino acid sequences of the core and NS5A regions in antiviral therapy for hepatitis C: a Japanese multi-center study.
BACKGROUND
Chronic hepatitis C (CHC) genotype 1b patients with high viral load are resistant to peginterferon (PEG-IFN) and ribavirin (RBV) combination therapy, especially older and female patients.


METHODS
To elucidate the factors affecting early and sustained viral responses (EVR and SVR), 409 genotype 1b patients CHC with high viral loads who had received 48 weeks of PEG-IFN/RBV therapy were enrolled. The amino acid (aa) sequences of the HCV core at positions 70 and 91 and of the interferon sensitivity determining region (ISDR) were analyzed. Host factors, viral factors, and treatment-related factors were subjected to multivariate analysis.


RESULTS
Male gender, low HCV RNA load, high platelet count, two or more aa mutations of ISDR, and wild type of core aa 70 were independent predictive factors for SVR. In patients with over 80% adherences to both PEG-IFN and RBV, male gender, mild fibrosis stage, and wild type of core aa 70 were independent predictors for SVR.


CONCLUSIONS
Independent predictive factors for SVR were: no aa substitution at core aa 70, two or more aa mutations in the ISDR, low viral load, high values of platelet count, mild liver fibrosis and male gender.
Okanoue
Takeshi
T
Hepatology Center, Saiseikai Suita Hospital, 1-2 Kawazonocho, Suita, 564-0013, Japan. okanoue@suita.saiseikai.or.jp
Itoh
Yoshito
Y
Hashimoto
Hiroaki
H
Yasui
Kohichiroh
K
Minami
Masahito
M
Takehara
Tetsuo
T
Tanaka
Eiji
E
Onji
Morikazu
M
Toyota
Joji
J
Chayama
Kazuaki
K
Yoshioka
Kentaro
K
Izumi
Namiki
N
Akuta
Norio
N
Kumada
Hiromitsu
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000494:pharmacology*; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology; D007564:Japan; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D011092:Polyethylene Glycols / Q000494:pharmacology; D011994:Recombinant Proteins; D012189:Retrospective Studies; D012254:Ribavirin / Q000494:pharmacology; D012307:Risk Factors; D012737:Sex Factors; D019562:Viral Load; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D055815:Young Adult; D012324:RNA-Dependent RNA Polymerase
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C417083:peginterferon alfa-2b