Antibody to Hepatitis B Core Antigen and Risk for Hepatitis C–Related Hepatocellular Carcinoma
A Prospective Study
- Kazuki Ikeda, MD;
- Hiroyuki Marusawa, MD, PhD;
- Yukio Osaki, MD;
- Takefumi Nakamura, MD, PhD;
- Naoto Kitajima, MD, PhD;
- Yukitaka Yamashita, MD, PhD;
- Masatoshi Kudo, MD, PhD;
- Tosiya Sato, PhD; and
- Tsutomu Chiba, MD, PhD
- From Kyoto University, Kyoto, Japan; Osaka Red Cross Hospital, Kitano Hospital, and Kinki University, Osaka, Japan; Kasai Municipal Hospital, Hyogo, Japan; and Wakayama Red Cross Medical Center, Wakayama, Japan.
Abstract
Background: Previous exposure to hepatitis B virus (HBV) and occult HBV infection may have an important role in the development of hepatocellular carcinoma (HCC) in patients with chronic liver disease related to hepatitis C virus (HCV).
Objective: To prospectively study the association between antibody to hepatitis B core antigen (anti-HBc) and clinical outcomes in patients with HCV-related chronic liver disease.
Design: Prospective observational study.
Setting: Kyoto University Hospital and 14 regional core hospitals in Japan.
Participants: 872 patients with chronic HCV infection (597 with chronic hepatitis and 275 with cirrhosis).
Measurements: Incidence of HCC on follow-up (from 1995 to 2005).
Results: Only 846 of the 872 enrolled patients were followed. Hepatocellular carcinoma occurred in 237 of 846 patients (28.0%) during follow-up. Among patients with cirrhosis, HCC was diagnosed in 85 of 141 patients (60.3%) with anti-HBc and 58 of 129 patients (45.0%) without HBV-related serologic markers. Of 224 patients with chronic hepatitis who had interferon monotherapy, 92 (41.1%) had sustained or transient disappearance of HCV RNA. None of the anti-HBc–negative patients who had a virologic response to interferon therapy developed HCC, whereas cancer was diagnosed in 4 of 37 anti-HBc–positive patients (10.8%) with a virologic response to interferon. On multivariate analysis using a Cox proportional hazards model, anti-HBc–positive results on serologic testing was an independent risk factor in patients with cirrhosis (incidence rate ratio, 1.58 [95% CI, 1.12 to 2.22]).
Limitations: The study included only 1 assessment of smoking and alcohol consumption at study entry and did not precisely determine the duration of smoking or alcohol use.
Conclusions: Anti-HBc–positive results on serologic testing are a marker of high risk for HCC among patients with HCV-related cirrhosis. Interferon therapy might be less effective in preventing HCC among patients with chronic hepatitis C who are anti-HBc–positive than in those with chronic hepatitis C who are anti-HBc–negative.
Article and Author Information
-
Acknowledgments: The authors thank the following physicians for their continued dedication: Y. Yamashita, MD, and K. Kaneshiro, MD, Miki City Hospital; S. Morishita, MD, Shimada Municipal Hospital; T. Eguchi, MD, Kitano Hospital; Y. Kimura, MD, T. Kurokami, MD, K. Matsumura, MD, Y. Kokuryu, MD, K. Kojima, MD, and K. Ito, MD, Shizuoka General Hospital; K. Mizuta, MD, and Y. Toda, MD, Shiga Medical Center for Adults; Y. Matsumori, MD, and Y. Yamamoto, MD, Takatsuki General Hospital; Y. Tanaka, MD, and K. Kajimura, MD, Kishiwada City Hospital; J. Shimamura, MD, and H. Shimomura, MD, Kurashiki Central Hospital; Y. Okabe, MD, and A. Orino, MD, Kobe City General Hospital; H. Azechi, MD, and O. Nishida, MD, Ohtsu Red Cross Hospital; T. Tamada, MD, Takatsuki Red Cross Hospital; K. Miura, MD, Kyoto Katsura Hospital; S. Ono, MD, Ako Municipal Hospital; T. Aoi, MD, M. Nabeshima, MD, and K. Mori, MD, Kyoto University Hospital.
-
Grant Support: By a Grant-in-Aid for Scientific Research (15209024 and 16790378) from the Japan Society for the Promotion of Science.
-
Potential Financial Conflicts of Interest: None disclosed.
-
Requests for Single Reprints: Tsutomu Chiba, MD, PhD, Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan; e-mail, chiba{at}kuhp.kyoto-u.ac.jp.
-
Current Author Addresses: Drs. Ikeda, Marusawa, and Chiba: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
-
Dr. Osaki: Osaka Red Cross Hospital, 5-30 Fudegasaki, Tennoji-ku, Osaka 543-8555, Japan.
-
Dr. Nakamura: Kitano Hospital, 2-4-20 Ogimachi, Kita-ku, Osaka 530-8480, Japan.
-
Dr. Kitajima: Kasai Municipal Hospital, 1-13 Yokoo, Hojyo-cho, Kasai 675-2393, Japan.
-
Dr. Yamashita: Japan Red Cross Society Wakayama Medical Center, 4-20 Komatsubaradori, Wakayama 640-8558, Japan.
-
Dr. Kudo: Kinki University School of Medicine, 377-2 Ohno-Higashi-cho, Osaka-Sayama 589-8511, Japan.
-
Dr. Sato: Department of Biostatistics, Kyoto University School of Public Health, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
-
Author Contributions: Conception and design: K. Ikeda, H. Marusawa, T. Chiba.
-
Analysis and interpretation of the data: K. Ikeda, H. Marusawa, T. Sato, T. Chiba.
-
Drafting of the article: K. Ikeda, H. Marusawa, T. Chiba.
-
Critical revision of the article for important intellectual content: K. Ikeda, H. Marusawa, M. Kudo, T. Sato, T. Chiba.
-
Final approval of the article: K. Ikeda, H. Marusawa, T. Sato, T. Chiba.
-
Provision of study materials or patients: K. Ikeda, H. Marusawa, Y. Osaki, T. Nakamura, N. Kitajima, Y. Yamashita, M. Kudo, T. Chiba.
-
Statistical expertise: T. Sato.
-
Obtaining of funding: H. Marusawa, T. Chiba.
-
Administrative, technical, or logistic support: K. Ikeda, H. Marusawa, Y. Osaki, T. Chiba.
-
Collection and assembly of data: K. Ikeda, H. Marusawa, Y. Osaki, T. Nakamura, N. Kitajima, Y. Yamashita, T. Chiba.
Related Clinical Content
Most Read
