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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, Tokyo-Chiba Hepatitis Research Group*
[+] Article and Author Information

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.


*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@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.


Ann Intern Med. 2005;142(2):105-114. doi:10.7326/0003-4819-142-2-200501180-00009
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Cirrhosis is a major risk factor for hepatocellular carcinoma and death. Antiviral therapy may be the most beneficial form of treatment for patients with chronic hepatitis C and cirrhosis, although this idea remains controversial. Retrospective cohort studies involving many patients with chronic hepatitis C showed that antiviral therapy reduces the risk for hepatocellular carcinoma in patients who have mild to moderate fibrosis (1114). Nishiguchi and colleagues (18) showed that interferon therapy can reduce the incidence of hepatocellular carcinoma in cirrhotic patients, regardless of interferon response. However, these investigators examined only 90 patients and reported a low rate of response to interferon therapy (sustained response, 16%). Cohort studies by Fattovich (7) and Niederau (8) and their colleagues showed that interferon therapy does not reduce the risk for hepatocellular carcinoma, perhaps because of the lower rate of liver tumor development (1% to 2% annually), low response rate (7% to 12%), and short follow-up period (4 to 5 years). A retrospective study by Serfaty and coworkers (9) showed that interferon treatment induces a favorable outcome for hepatocellular carcinoma development or decompensation; however, their study included only 103 patients. Because of the contradictory findings and various built-in biases of previous studies, we designed a prospective study to clarify the exact role of interferon therapy in reducing the rate of hepatocellular carcinoma over a 7-year observation period.

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Figures

Grahic Jump Location
Figure 1.
Flow diagram of the trial.

HCC = hepatocellular carcinoma; IFN = interferon; Non-SVR = nonsustained virologic response; SVR = sustained virologic response.

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Grahic Jump Location
Figure 2.
Cumulative incidence of hepatocellular carcinoma (HCC) (age-stratified analysis).

The Kaplan–Meier method was used to gauge the cumulative incidence of hepatocellular carcinoma development in interferon-treated and untreated patients stratified according to age (<50 years, 50 to 59 years, ≥60 years).

Grahic Jump Location
Grahic Jump Location
Figure 3.
Patient survival (age-stratified analysis).

The Kaplan–Meier method was used to evaluate survival of interferon-treated and untreated patients according to age (<50 years, 50 to 59 years, ≥60 years).

Grahic Jump Location

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Summary for Patients

Long-Term Effects of Antiviral Treatment for Hepatitis C

The summary below is from the full report titled “Antiviral Therapy for Cirrhotic Hepatitis C: Association with Reduced Hepatocellular Carcinoma Development and Improved Survival.” It is in the 18 January 2005 issue of Annals of Internal Medicine (volume 142, pages 105-114). The authors are Y. Shiratori, Y. Ito, O. Yokosuka, F. Imazeki, R. Nakata, N. Tanaka, Y. Arakawa, E. Hashimoto, K. Hirota, H. Yoshida, Y. Ohashi, and M. Omata, for the Tokyo-Chiba Hepatitis Research Group.

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