Antiviral Therapy for Cirrhotic Hepatitis C: Association with Reduced Hepatocellular Carcinoma Development and Improved Survival

Antiviral Therapy for Cirrhotic Hepatitis C: Association with Reduced Hepatocellular Carcinoma Development and Improved Survival

Yasushi Shiratori, MD;
Yoichi Ito, MHlth Sc;
Osamu Yokosuka, MD;
Fumio Imazeki, MD;
Ryo Nakata, MD;
Naohide Tanaka, MD;
Yasuyuki Arakawa, MD;
Etsuko Hashimoto, MD;
Katsutaro Hirota, MD;
Haruhiko Yoshida, MD;
Yasuo Ohashi, PhD;
Masao Omata, MD; and
for the Tokyo-Chiba Hepatitis Research Group*

From University of Tokyo, Japanese Red Cross Medical Center, Nippon University School of Medicine, and Tokyo Women's Medical College, Tokyo; Chiba University School of Medicine, Chiba; and Mito Saiseikai Hospital, Ibaraki, Japan.

Abstract

Background: Although cirrhosis is a major risk factor for development of hepatocellular carcinoma, no definitive prospective analyses have assessed the long-term efficacy of antiviral therapy in cirrhotic patients.

Objective: To elucidate the role of antiviral therapy in the suppression of liver tumors and survival over a long-term follow-up period.

Design: Prospective cohort study.

Setting: 25 clinical centers.

Patients: 345 patients with chronic hepatitis C and cirrhosis enrolled in previous trials.

Intervention: 271 patients received 6 to 9 million U of interferon 3 times weekly for 26 to 88 weeks; 74 received no treatment.

Measurements: Blood tests and abdominal ultrasonography were done regularly to detect hepatocellular carcinoma.

Results: Hepatocellular carcinoma was detected in 119 patients during a 6.8-year follow-up: 84 (31%) in the interferon-treated group and 35 (47%) in the untreated group. Cumulative incidence of hepatocellular carcinoma among interferon-treated patients was significantly lower than in untreated patients (Cox model: age-adjusted hazard ratio, 0.65 [95% CI, 0.43 to 0.97]; P = 0.03), especially sustained virologic responders. A total of 69 patients died during follow-up: 45 (17%) in the treated group and 24 (32%) in the untreated group. Interferon-treated patients had a better chance of survival than the untreated group (Cox model: age-adjusted hazard ratio, 0.54 [CI, 0.33 to 0.89]; P = 0.02). This was especially evident in sustained virologic responders.

Limitation: This was not a randomized, controlled study. Patients enrolled in the control group had declined to receive interferon treatment even though they were eligible for treatment.

Conclusion: Interferon therapy for cirrhotic patients with chronic hepatitis C, especially those in whom the infection had been cured, inhibited the development of hepatocellular carcinoma and improved survival.

Article and Author Information

*For members of the Tokyo-Chiba Hepatitis Research Group, see the Appendix.
Potential Financial Conflicts of Interest: None disclosed.
Requests for Single Reprints: Yasushi Shiratori, MD, Department of Gastroenterology, Hepatology, and Infectious Diseases, Okayama University School of Medicine, 2-5-1 Shikata-cho, Okayama-shi, Okayama 700-8558, Japan; e-mail, shirato{at}cc.okayama-u.ac.jp.
Current Author Addresses: Dr. Shiratori: Department of Gastroenterology, Hepatology, and Infectious Diseases, Okayama University School of Medicine, 2-5-1 Shikata-cho, Okayama-shi, Okayama 700-8558, Japan.
Drs. Yoshida and Omata: Department of Gastroenterology, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan.
Drs. Ito and Ohashi: Department of Epidemiology and Biostatistics, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan.
Drs. Yokosuka and Imazeki: First Department of Internal Medicine, Chiba University School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba, Japan.
Dr. Nakata: Department of Gastroenterology, Japanese Red Cross Medical Center, 4-1-22 Hiroo, Shibuya-ku, Tokyo, Japan.
Drs. Tanaka and Arakawa: Third Department of Internal Medicine, Nippon University School of Medicine, 30-1 Ohyaguchi Uemachi, Itabashi-ku, Tokyo, Japan.
Dr. Hashimoto: Department of Medicine, Institute of Gastroenterology, Tokyo Women's Medical College, 8-1 Kawada-cho, Shin'juku-ku, Tokyo, Japan.
Dr. Hirota: Gastroenterology Unit, Mito Saiseikai Hospital, Mito-shi, Ibaraki, Japan.
Author Contributions: Conception and design: Y. Shiratori, Y. Ito, O. Yokosuka, F. Imazeki, R. Nakata, N. Tanaka, Y. Arakawa, E. Hashimoto, K. Hirota, H. Yoshida, Y. Ohashi, M. Omata.
Analysis and interpretation of the data: Y. Shiratori, Y. Ito, Y. Ohashi, M. Omata.
Drafting of the article: Y. Shiratori, M. Omata.
Critical revision of the article for important intellectual content: Y. Shiratori, Y. Ito, O. Yokosuka, F. Imazeki, R. Nakata, N. Tanaka, Y. Arakawa, E. Hashimoto, K. Hirota, H. Yoshida, Y. Ohashi, M. Omata.
Final approval of the article: Y. Shiratori, Y. Ito, O. Yokosuka, F. Imazeki, R. Nakata, N. Tanaka, Y. Arakawa, E. Hashimoto, K. Hirota, H. Yoshida, Y. Ohashi, M. Omata.
Provision of study materials or patients: Y. Shiratori, O. Yokosuka, F. Imazeki, R. Nakata, N. Tanaka, Y. Arakawa, E. Hashimoto, K. Hirota, H. Yoshida, M. Omata.
Statistical expertise: Y. Shiratori, Y. Ito, Y. Ohashi.
Administrative, technical, or logistic support: Y. Shiratori, M. Omata.
Collection and assembly of data: O. Yokosuka, F. Imazeki, R. Nakata, N. Tanaka, Y. Arakawa, E. Hashimoto, K. Hirota, H. Yoshida.