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; Tsutomu Chiba, MD, PhD
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, firstname.lastname@example.org.
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.
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).
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.
Prospective observational study.
Kyoto University Hospital and 14 regional core hospitals in Japan.
872 patients with chronic HCV infection (597 with chronic hepatitis and 275 with cirrhosis).
Incidence of HCC on follow-up (from 1995 to 2005).
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]).
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.
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.
Ikeda K, Marusawa H, Osaki Y, Nakamura T, Kitajima N, Yamashita Y, et al. Antibody to Hepatitis B Core Antigen and Risk for Hepatitis C–Related Hepatocellular Carcinoma: A Prospective Study. Ann Intern Med. 2007;146:649–656. doi: 10.7326/0003-4819-146-9-200705010-00008
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Published: Ann Intern Med. 2007;146(9):649-656.
Gastroenterology/Hepatology, Gastrointestinal Cancer, Hematology/Oncology, Infectious Disease, Liver Cancer.
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