Objective To evaluate serum levels of prolyl-hydroxylase and helical domain of Type IV degrees collagen, markers of hepatic fibrogenesis, in patients with HCV-positive chronic liver disease and the effects of interferon therapy on these markers. Design Prolyl-hydroxylase and Type IV degrees collagen were determined before therapy and each month during the treatment and follow-up. Methods Fifty-seven HCV-positive patients were studied. All the subjects received alpha 2a recombinant interferon, 6 MU subcutaneously three times a week for 4 weeks, followed by 3 MU thrice weekly for 5 months. After cessation of treatment, each patient was followed for 12 months. Prolyl-hydroxylase and helical domain of Type IV degrees collagen were measured by using immunoenzymatic methods. HCV-RNA and HCV genotype were determined according to the method of Okamoto. Results In the patients prolyl-hydroxylase (39.8 +/- 8.9 ng/ml) was not different from controls (39.1 +/- 5.9 ng/ml). On the contrary, the patients showed a mean Type IV degrees collagen (133.6 +/- 93.3 ng/ml) significantly (P < 0.01) higher than controls (100.2 +/- 10.5 ng/ml). A good relationship between the degree of liver fibrosis and the Type IV degrees collagen serum level was found (r = 0.68; P < 0.005). In both responders and non-responders the Type IV degrees collagen levels decreased during interferon therapy. During the follow-up, in responders the Type IV degrees collagen did not show modifications, while in nonresponders/relapsers it returned rapidly to the pretreatment levels (139.1 +/- 100.7 ng/ml). Conclusion In HCV-positive chronic liver disease, prolylhydroxylase is not a good marker of hepatic fibrosis, while Type IV degrees collagen is a useful tool for evaluating fibrogenic activity. Interferon seems to be able to reduce the liver fibrosis even without the inhibition of viral replication and independently from liver necrosis. (C) 1998 Rapid Science Ltd.