Changes in sequences of core region, interferon sensitivity-determining region and interferon and ribavirin resistance-determining region of hepatitis C virus genotype 1 during interferon-alpha and ribavirin therapy, and efficacy of retreatment.
OBJECTIVE
Some regions associated with sensitivity to interferon-α and ribavirin have been identified in the hepatitis C virus (HCV) genome, including amino acid 70 in the core region (core a.a. 70), a.a. 2209-2248 (interferon sensitivity-determining region, ISDR) and a.a. 2334-2379 (interferon and ribavirin resistance-determining region, IRRDR).


METHODS
We examined changes in the sequences of these regions in 25 patients with chronic HCV genotype 1 infection who had not had sustained virological response (SVR) to interferon-α and ribavirin for 24-48 weeks and subsequently received retreatment for 48-72 weeks.


RESULTS
At baseline, the core a.a. 70 was mutant (resistant) type in seven patients. At the start of retreatment, the core a.a. 70 had changed from sensitive to resistant type in 2 patients, and SVR was not achieved by retreatment. The ISDR variations were resistant type (0-1 mutations) in 17 patients at baseline. After 2 weeks of treatment, amino acid change was found in two patients; in one, the substitutions returned to baseline status after treatment, and in the other, the substitution persisted. At the start of retreatment, ISDR sequences had changed from resistant to sensitive type in two patients and SVR was achieved and from sensitive to resistant type in three patients and SVR was not achieved. The IRRDR variations were resistant type (<6 mutations) in 19 patients at baseline and at the start of retreatment.


CONCLUSIONS
Sequences of the core region and ISDR sometimes change during anti-HCV therapy, potentially affecting the outcomes of retreatment.
Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka             Center for the Advancement of Higher Education, Faculty of Engineering, Kinki University, Hiroshima, Japan.
Ritsuzo
R
Kozuka
Masaru
M
Enomoto
Hoang
H
Hai
Tomohiro
T
Ogawa
Mika
M
Nakaya
Atsushi
A
Hagihara
Hideki
H
Fujii
Sawako
S
Kobayashi
Shuji
S
Iwai
Hiroyasu
H
Morikawa
Akihiro
A
Tamori
Norifumi
N
Kawada