CHANGES IN SERUM LEVELS OF METALLOPROTEINASES AND THEIR INHIBITORS BYTREATMENT OF CHRONIC HEPATITIS-C WITH INTERFERON

We treated 18 patients with chronic hepatitis C by recombinant interfe ron-alpha (6 MIU for 24 weeks). In seven patients, serum aminotransfer ase levels declined to normal (responders). To evaluate the effect of interferon on matrix metalloproteinases (MMPs) and their inhibitors, n amely tissue inhibitors of metalloproteinases (TIMPs), the serum level s of these enzymes were determined by enzyme immunoassay (EIA) using a specific monoclonal antibody. In responders, there was a tendency, bu t not a significant one, towards either an increase in serum MMP 1 lev els or a decrease in serum TIMP 1 levels. In contrast, in nonresponder s, both a significant decrease in MMP 1 and MMP 3 and a significant in crease in TIMP 1 were observed. The number of cases of either increase in serum MMP levels or decrease in serum TIMP levels was significantl y larger in responders than in nonresponders. Furthermore, the ratio o f MMP 1 to TIMP 1 significantly increased in responders, suggesting th at the balance between matrix formation and degradation in hepatic fib rosis tended to move toward degradation, These data indicate that inte rferon may exert a beneficial effect on hepatic fibrosis in parallel w ith improvement of aminotransferase activity.