Hepatic Fibrosis Regresses in Interferon-Responsive Hepatitis C Patients

WESTPORT, Apr 05 (Reuters Health) - Hepatitis C˝related hepatic fibrosis regresses in patients who experience a sustained virologic response to interferon therapy, according to a report in the April 4th issue of Annals of Internal Medicine.

Dr. Yasushi Shiratori, of the University of Tokyo in Japan, and colleagues examined liver biopsy specimens obtained 1 to 10 years apart from 593 patients with hepatitis C-related hepatic fibrosis, 487 of whom had received interferon treatment.

Among interferon-treated patients, 183 had a sustained virologic response. defined as a loss of serum hepatitis C viral RNA, and 304 had a nonsustained response, the authors report.

The biopsy activity grade, measured on a four-point scale from none to severe, improved in 89% of the patients with a sustained response, compared with 50% to 60% of patients with a nonsustained response and untreated patients, the results indicated.

Furthermore, the degree of fibrosis, measured on a five-point scale from none to cirrhosis, regressed in 59% of patients with a sustained virologic response and progressed in only 3%. In contrast, fibrosis progressed in 38% of untreated patients (and regressed in 5%) and progressed in 24% of patients with nonsustained response (and regressed in 19%), the investigators note.

The rate of fibrosis regression was 0.28 activity grade per year in patients with a sustained response, the researchers observe. On the other hand, fibrosis progressed at the rate of 0.10 grade per year in untreated patients and 0.02 grade per year in patients with a nonsustained virologic response.

"Comparison of fibrosis rates between treated and untreated patients carries built-in bias because the untreated patients had a milder stage of fibrosis and inflammatory activity," the investigators acknowledge.

Nevertheless, they conclude, "interferon therapy seemed to reduce the progression of hepatic fibrosis and cause regression of fibrosis in patients with virologic response to treatment, and it reduced progression of hepatic fibrosis in patients with nonsustained virologic response." Ann Intern Med 2000;132:517-524.


Histologic improvement of fibrosis in patients with hepatitis C who have sustained response to interferon therapy Ann Intern Med 2000 Apr 4;132(7):517-24

Shiratori Y, Imazeki F, Moriyama M, Yano M, Arakawa Y, Yokosuka O, Kuroki T,
Nishiguchi S, Sata M, Yamada G, Fujiyama S, Yoshida H, Omata M

Department of Internal Medicine, University of Tokyo and Nihon University
School of Medicine, Japan.

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.

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 (+/-SE) 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.

PMID: 10744587, UI: 20186674