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 oligoa denylate synthetase (2-5 OAS) in serum and changes induced by the trea tment with interferon are relevant factors in remission of chronic hep atitis C. Seventeen out of 30 adult patients with chronic hepatitis C were randomized to receive recombinant alpha-2b interferon at the dosa ge of 3 MU three times weekly. By the end of the third month, nine pat ients had normalized transaminase levels and continued to receive 3 MU of interferon for an additional 3 months, whereas in eight non-respon ders the dosage was increased to 6 MU for the same period of time. A s ingle patient responded to the increased dosage. Baseline 2-5 OAS seru m activity was significantly higher in patients with chronic hepatitis when compared with normal controls. Follow-up on the 13 untreated cas es showed that 2-5 OAS elevation was stable and unrelated to concomita nt infections. Comparison of responders and non-responders showed that the latter had higher baseline 2-5 OAS activity, tended to have an ea rlier and higher peak in the enzyme during the first 4 weeks of treatm ent, and maintained higher levels during the first 3 months of therapy . The increased dosage of interferon in this group led to an additiona l, although temporary, increase in 2-5 OAS. Our data suggest that HCV infection by itself induces elevated 2-5 OAS levels. The paradoxical i ncrease in non-responders indicates that monitoring of the enzyme in s erum 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.