Histologic improvement of fibrosis in patients with hepatitis C who have sustained response to interferon therapy

Background: Short-term histologic improvement in hepatitis C-related hepatic fibrosis has been noted in studies with more than 2 years of follow-up, but the long-term effects of interferon therapy on hepatic fibrosis remain unclear. Objective: To assess changes in hepatic fibrosis after interferon therapy in patients with chronic hepatitis C. Design: Retrospective cohort study. Setting: 7 university hospitals and 1 national hospital in Japan. Patients: 593 patients with chronic hepatitis C who underwent a paired liver biopsy from 1987 to 1997. Of these, 487 patients received interferon therapy and 106 patients were untreated. Intervention: Patients in the treatment group received a 2- to 6-month course of interferon within 6 months after the initial biopsy. Measurements: Fibrosis and inflammatory activity in paired biopsy samples obtained a median of 3.7 years apart (range, 1 to 10 years) were graded by using the criteria of Desmet and colleagues (F0 to F4) and those of the French METAVIR Cooperative Study Group (A0 to A3), respectively. Changes in fibrosis staging and activity scores and yearly rates of fibrosis progression and regression were calculated. Results: 183 of the 487 interferon-treated patients showed a sustained virologic response. Activity grade was unchanged in most of the untreated patients and improved in 89% (CI, 83% to 93%) of patients with a sustained virologic response. A sustained response to interferon was associated with a mean (ISE) reduction in fibrosis score of -0.60 +/- 0.07 at less than 3 years of follow-up and -0.88 +/- 0.08 at 3 years or more of follow-up. The rate of fibrosis progression was -0.28 +/- 0.03 unit/y (regression) in patients with sustained response, 0.02 +/- 0.02 unit/y in patients with nonsustained response (P < 0.001), and 0.10 +/- 0.02 unit/y in untreated patients. Conclusion: Although the time between biopsies partly affected the patient's clinical course, the differences observed here suggest that in patients with chronic hepatitis C, regression of fibrosis is associated with sustained virologic response to interferon therapy.