Changes in serum tissue inhibitor of matrix metalloproteinase-1 after interferon alpha treatment in chronic hepatitis C

Background/Aims: The aim of this study was to evaluate the effect of interf eron alpha on the metabolism of hepatic fibrosis in chronic hepatitis C, mo nitoring serum tissue inhibitor of matrix metallo-proteinase-1(TIMP-1) and N-terminal propeptide of type III procollagen (PIIINP) reflecting fibrolysi s and fibrogenesis, respectively. Methods: Serum levels of TIMP-1 and PIIINP were serially measured in 112 tr eated and 31 untreated patients with chronic hepatitis C during and after i nterferon alpha treatment. Furthermore, the relationships between these ser um markers and the grades of hepatic fibrosis after interferon therapy were also investigated. Results: Serum pretreatment levels of TIMP-1 and PIIINP in non-responders w ere significantly higher than those in sustained and transient responders, but these levels were not different in the latter two groups. Serum TIMP-1 levels decreased significantly during and after treatment in sustained resp onders, and decreased temporarily at the end of treatment in transient resp onders, although these levels were unchanged during and after treatment in non-responders and untreated patients. In contrast, serum PIIINP levels dec reased significantly during and after treatment in all treated groups, but were unchanged in untreated patients. Histological examination 12 months af ter interferon was completed demonstrated that hepatic fibrosis improved in sustained responders and was unchanged in transient and non-responders, bu t progressed in untreated patients. Conclusion: These results suggest that interferon alpha treatment of chroni c hepatitis C may improve hepatic fibrosis in sustained responders by the a cceleration of fibrolysis as well as the inhibition of fibrogenesis, and th at it may suppress the progression of hepatic fibrosis in non-sustained res ponders by the inhibition of fibrogenesis.