Open Access Research article

Multiplicative synergistic risk of hepatocellular carcinoma development among hepatitis B and C co-infected subjects in HBV endemic area: a community-based cohort study

Jin-Kyoung Oh1, Hai-Rim Shin12*, Min Kyung Lim1, Heeyoun Cho1, Dong-Il Kim3, Youngmee Jee45, Haesun Yun5 and Keun-Young Yoo6

Author affiliations

1 National Cancer Control Institute, National Cancer Center, Goyang, Republic of Korea

2 Non Communicable Diseases and Health Promotion, World Health Organization Western Pacific Regional Office, 1000 UN Avenue, Manila, Philippines

3 Department of Occupational and Environmental Medicine, Samsung Medical Center, Sungkunkwan University School of Medicine, Suwon, Republic of Korea

4 Expanded Programme on Immunization, World Health Organization Western Pacific Regional Office, Manila, Philippines

5 Division of Enteric and Hepatitis Viruses, National Institute of Health, Korea Centers for Disease Control and Prevention, Osong, Republic of Korea

6 Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea

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Citation and License

BMC Cancer 2012, 12:452  doi:10.1186/1471-2407-12-452

Published: 5 October 2012



There has been limited study on the effect of infection with different hepatitis C virus (HCV) genotypes on the risk of hepatocellular carcinoma (HCC) in hepatitis B virus (HBV) endemic regions of Asia.


Hazard ratios of HCC development were estimated for HBV and HCV co-infected subjects among a community-based prospective cohort. HCV genotype was determined in HCV RNA-positive samples. Incident HCC cases were identified through linkage to the cancer registry.


HCC incidence was 79 per 100,000 person-years in the study population (50 incident cases among 6,694 individuals within 63,170 person-years with an average of 9.4 years of follow-up); seroprevalence of HBsAg and anti-HCV was 5.2% and 5.6%. Adjusted hazard ratios of HCC by HBsAg positivity and anti-HCV positivity were 13.3 (CI: 7.3-24.4) and 6.7 (CI: 3.6-12.6). HRs of HBV and HCV monoinfection, and HBV/HCV coinfection were 17.1 (CI: 8.4-34.8), 10.4 (CI: 4.9-22.1) and 115.0 (CI: 32.5-407.3). Multiplicative synergistic effect of HBV/HCV coinfection on HCC risk was also observed (synergy index: 4.5, CI: 1.3-15.5). Infection with HCV genotype 1 (HR: 29.7, CI: 13.6-46.8) and mixed infection with genotype 1 and 2 (HR: 68.7, CI: 16.4-288.4) significantly elevated HCC risk, much higher than HBV infection.


The effect of differences in HCV genotype and the multiplicative synergistic effect of HBV/HCV coinfection on HCC risk shown in the present study underline the need for comprehensive identification of hepatitis infection status in order to prevent and control HCC in this HBV endemic area.

Hepatitis B virus; Hepatitis C virus; Hepatocellular carcinoma; Cohort study