2'-,5'-Oligoadenylate synthetase response ratio predicting virological response to PEG-interferon-alpha2b plus ribavirin therapy in patients with chronic hepatitis C.
OBJECTIVE
Although all the mechanisms of elimination of hepatitis C virus (HCV) by Interferon (IFN) have not been fully elucidated, the 2'-5'-oligoadenylate (2-5A) system is one of the mechanisms of the antiviral effect of IFN. Consequently, the measurement of 2'-5'-oligoadenylate synthetase (2-5AS) activity could be useful for the evaluation of IFN treatment. This retrospective study was aimed at assessing whether 2-5AS activity functions as a clinical marker of virological response to PEG-interferon-alpha2b (PEG-IFN) plus ribavirin therapy of chronic hepatitis C.


METHODS
The 32 patients included in this study had high viral loads of serum HCV-RNA of genotype 1b with chronic hepatitis C. All the patients received a regimen of PEG-IFN plus ribavirin for 48 weeks, and were then divided into two groups: one group (effective group) with undetectable serum HCV-RNA levels at 24 weeks (n = 22) of therapy, the other group (ineffective group) with persistent presence of HCV-RNA in serum at 24 weeks (n = 10). The 2-5AS activity in serum was measured 2, 8 and 12 weeks before initial administration.


RESULTS
The 2-5AS response ratio (measured value/measured value of baseline 2-5AS) at 2, 8 and 12 weeks after the administration in the effective group was significantly higher than that in the ineffective group.


CONCLUSIONS
These results suggest that the ratio of 2-5AS is closely related to the antiviral effect, and that the measurement of 2-5AS response ratio may be a useful clinical parameter of virological response to PEG-IFN plus ribavirin therapy of chronic hepatitis C.
Kim
K-I
KI
Department of Pharmacy, Kobe Asahi Hospital, Kobe, Japan.
Kim
S-R
SR
Sasase
N
N
Taniguchi
M
M
Harada
S
S
Kinoshita
K
K
Kim
S-H
SH
Akimoto
Y
Y
Shikata
M
M
Kimura
N
N
Izawa
S
S
Ohtani
A
A
Nakao
K
K
Motojima
M
M
Kinoshita
M
M
Hirai
M
M
Ohzu
M
M
Hirooka
T
T
Nabeshima
S
S
Ishii
F
F
Tanaka
K
K
Hotta
H
H
D015088:2',5'-Oligoadenylate Synthetase / Q000187:drug effects / Q000378:metabolism*; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000494:pharmacology / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012189:Retrospective Studies; D012254:Ribavirin / Q000494:pharmacology / Q000627:therapeutic use*
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D015088:2',5'-Oligoadenylate Synthetase; C100416:peginterferon alfa-2a