Changes of serum 2',5'-oligoadenylate synthetase activity during interferon treatment of chronic hepatitis C.
It was our aim to evaluate whether the baseline activity of 2-5 oligoadenylate synthetase (2-5 OAS) in serum and changes induced by the treatment with interferon are relevant factors in remission of chronic hepatitis C. Seventeen out of 30 adult patients with chronic hepatitis C were randomized to receive recombinant alpha-2b interferon at the dosage of 3 MU three times weekly. By the end of the third month, nine patients had normalized transaminase levels and continued to receive 3 MU of interferon for an additional 3 months, whereas in eight non-responders the dosage was increased to 6 MU for the same period of time. A single patient responded to the increased dosage. Baseline 2-5 OAS serum activity was significantly higher in patients with chronic hepatitis when compared with normal controls. Follow-up on the 13 untreated cases showed that 2-5 OAS elevation was stable and unrelated to concomitant infections. Comparison of responders and non-responders showed that the latter had higher baseline 2-5 OAS activity, tended to have an earlier and higher peak in the enzyme during the first 4 weeks of treatment, and maintained higher levels during the first 3 months of therapy. The increased dosage of interferon in this group led to an additional, although temporary, increase in 2-5 OAS. Our data suggest that HCV infection by itself induces elevated 2-5 OAS levels. The paradoxical increase in non-responders indicates that monitoring of the enzyme in serum does not predict the response to interferon. The role of the 2-5 OAS pathway in inducing the antiviral state in HCV infection should be further evaluated at tissue level.
Solinas
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Instituti di Patologia Medica e Clinica Medica dell'Università di Sassari, Sassari, Italy.
Cossu
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Poddighe
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P
Tocco
A
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Deplano
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A
Garrucciu
G
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Diana
M S
MS
D015088:2',5'-Oligoadenylate Synthetase / Q000097:blood*; D000328:Adult; D002908:Chronic Disease; D005260:Female; D006526:Hepatitis C / Q000201:enzymology* / Q000628:therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D000637:Transaminases / Q000097:blood
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D000637:Transaminases; D015088:2',5'-Oligoadenylate Synthetase