Histologic Improvement of Fibrosis in Patients with Hepatitis C Who Have Sustained Response to Interferon Therapy

  1. Yasushi Shiratori, MD;
  2. Fumio Imazeki, MD;
  3. Mitsuhiko Moriyama, MD;
  4. Michitami Yano, MD;
  5. Yasuyuki Arakawa, MD;
  6. Osamu Yokosuka, MD;
  7. Tetsuo Kuroki, MD;
  8. Shuhei Nishiguchi, MD;
  9. Michio Sata, MD;
  10. Gotarou Yamada, MD;
  11. Shigetoshi Fujiyama, MD;
  12. Haruhiko Yoshida, MD; and
  13. Masao Omata, MD
  1. From University of Tokyo and Nihon University School of Medicine, Tokyo; Chiba University School of Medicine, Chiba; National Nagasaki Central Hospital, Nagasaki; Osaka City University School of Medicine, Osaka; Kurume University School of Medicine, Fukuoka; Kawasaki University School of Medicine, Okayama; and Kumamoto University School of Medicine, Kumamoto, Japan.

    Abstract

    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 (±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.

    Article and Author Information

    • † Deceased.

    • Grant Support: By the Ministry of Health and Welfare of Japan as one of the Comprehensive 10-Year Strategy for Cancer Control Projects.

    • Requests for Single Reprints: Yasushi Shiratori, MD, Division of Gastroenterology-Hepatology, Department of Internal Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

    • Requests To Purchase Bulk Reprints (minimum, 100 copies): the Reprints Coordinator; phone, 215-351-2657; e-mail, reprints{at}mail.acponline.org.

    • Current Author Addresses: Drs. Shiratori, Yoshida, and Omata: Division of Gastroenterology-Hepatology, Department of Internal Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

    • Drs. Imazeki and Yokosuka: First Department of Internal Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8677, Japan.

    • Drs. Moriyama and Arakawa: Third Department of Internal Medicine, Nihon University, 30-1 Oyaguchi, Itabashi-ku, Tokyo 173-8610, Japan.

    • Dr. Yano: Department of Clinical Research, National Nagasaki Chuo Hospital, 2-1001-1, Kuhara, Ohmura, Nagasaki 856-0835, Japan.

    • Dr. Nishiguchi: Third Department of Internal Medicine, Osaka City University, 1-5-7 Asahi-cho, Abeno-ku, Osaka 545-8586, Japan.

    • Dr. Sata: Second Department of Internal Medicine, Kurume University, 67 Asahi-cho, Kurume, Fukuoka 830-0011, Japan.

    • Dr. Yamada: Liver Unit, Kawasaki Medical School, 2-1-80 Nakayama-shita, Okayama, Okayama 700-0821, Japan.

    • Dr. Fujiyama: Third Department of Internal Medicine, 1-1-1 Honjo, Kumamoto, Kumamoto 860-8556, Japan.

    • Author Contributions: Conception and design: Y. Shiratori, F. Imazeki, M. Moriyama, M. Yano, Y. Arakawa, O. Yokosuka, T. Kuroki, S. Nishiguchi, M. Sata, G. Yamada, S. Fujiyama, H. Yoshida, M. Omata.

    • Analysis and interpretation of the data: Y. Shiratori, H. Yoshida, M. Omata.

    • Drafting of the article: Y. Shiratori.

    • Critical revision of the article for important intellectual content: Y. Shiratori, F. Imazeki, M. Moriyama, M. Yano, Y. Arakawa, O. Yokosuka, T. Kuroki, S. Nishiguchi, M. Sata, G. Yamada, S. Fujiyama, H. Yoshida, M. Omata.

    • Final approval of the article: Y. Shiratori, F. Imazeki, M. Moriyama, M. Yano, Y. Arakawa, O. Yokosuka, T. Kuroki, S. Nishiguchi, M. Sata, G. Yamada, S. Fujiyama, H. Yoshida, M. Omata.

    • Provision of study materials or patients: Y. Shiratori, F. Imazeki, M. Moriyama, M. Yano, Y. Arakawa, O. Yokosuka, T. Kuroki, S. Nishiguchi, M. Sata, G. Yamada, S. Fujiyama, H. Yoshida, M. Omata.

    • Statistical expertise: Y. Shiratori, H. Yoshida, M. Omata.

    • Obtaining of funding: M. Omata.

    • Administrative, technical, or logistic support: Y. Shiratori, M. Omata.

    • Collection and assembly of data: Y. Shiratori, F. Imazeki, M. Moriyama, M. Yano, Y. Arakawa, O. Yokosuka, T. Kuroki, S. Nichiguchi, M. Sata, G. Yamada, S. Fujiyama, H. Yoshida, M. Omata.

    Summary for Patients

    • Summaries for Patients:Improvement in Liver Fibrosis in Patients with Hepatitis C Who Respond to Interferon Treatment Ann Intern Med April 4, 2000 132:517
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    1. Ann Intern Med April 4, 2000 vol. 132 no. 7 517-524
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