title: Multiplicative synergistic risk of hepatocellular carcinoma development among hepatitis B and C co-infected subjects in HBV endemic area: a community-based cohort study.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: National Cancer Control Institute, National Cancer Center, Goyang, Republic of Korea.
authors.forename: Jin-Kyoung
authors.initials: JK
authors.lastname: Oh
authors.forename: Hai-Rim
authors.initials: HR
authors.lastname: Shin
authors.forename: Min Kyung
authors.initials: MK
authors.lastname: Lim
authors.forename: Heeyoun
authors.initials: H
authors.lastname: Cho
authors.forename: Dong-Il
authors.initials: DI
authors.lastname: Kim
authors.forename: Youngmee
authors.initials: Y
authors.lastname: Jee
authors.forename: Haesun
authors.initials: H
authors.lastname: Yun
authors.forename: Keun-Young
authors.initials: KY
authors.lastname: Yoo
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000453:epidemiology / Q000821:virology*; D015331:Cohort Studies; D060085:Coinfection / Q000150:complications* / Q000821:virology; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D006509:Hepatitis B / Q000097:blood / Q000150:complications* / Q000821:virology; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics / Q000302:isolation & purification; D006526:Hepatitis C / Q000097:blood / Q000150:complications* / Q000235:genetics / Q000821:virology; D018937:Hepatitis C Antibodies / Q000097:blood; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000453:epidemiology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012367:RNA, Viral / Q000235:genetics; D056910:Republic of Korea / Q000453:epidemiology; D012307:Risk Factors; D016036:Seroepidemiologic Studies
chemical_list: D006514:Hepatitis B Surface Antigens; D018937:Hepatitis C Antibodies; D012367:RNA, Viral