2′-,5′-Oligoadenylate synthetase response ratio predicting virological response to PEG-interferon-α2b plus ribavirin therapy in patients with chronic hepatitis C

• Published in: Journal of clinical pharmacy and therapeutics Vol. 31; no. 5; pp. 441 - 446
• Main Authors: Kim, K.-I., Kim, S.-R., Sasase, N., Taniguchi, M., Harada, S., Kinoshita, K., Kim, S.-H., Akimoto, Y., Shikata, M., Kimura, N., Izawa, S., Ohtani, A., Nakao, K., Motojima, M., Kinoshita, M., Hirai, M., Ohzu, M., Hirooka, T., Nabeshima, S., Ishii, F., Tanaka, K., Hotta, H.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-10-2006; Blackwell
• Subjects: 2′,5′‐oligoadenylate synthetase; 5′-oligoadenylate synthetase; Biological and medical sciences; chronic hepatitis C; Human viral diseases; Infectious diseases; Medical sciences; PEG-interferon-α2b; Pharmacology. Drug treatments; ribavirin; Viral diseases; Viral hepatitis; Antineoplastic agent; Human; Enzyme; Cytokine; Prediction; chronic hepatitis C; Hepatic disease; Ribavirin; Infection; Ethylene oxide polymer; Treatment; Interferon alpha 2b; 2',5'-oligoadenylate synthetase; Ligases; Viral disease; PEG-interferon-α2b; Nucleoside analog; Digestive diseases; Antiviral; Viral hepatitis C
• ISSN: 0269-4727; 1365-2710
• DOI: 10.1111/j.1365-2710.2006.00761.x

Summary
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‐α2b (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.