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

BMC Cancer

Keun-Young Yoo⁵  Haesun Yun⁴  Youngmee Jee⁴  Dong-Il Kim²  Heeyoun Cho³  Min Kyung Lim³  Hai-Rim Shin¹  Jin-Kyoung Oh³ 

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

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

[3]National Cancer Control Institute, National Cancer Center, Goyang, Republic of Korea

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

[5]Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea

关键词: Cohort study;    Hepatocellular carcinoma;    Hepatitis C virus;    Hepatitis B virus;   

Others  :  1080157
DOI  :  10.1186/1471-2407-12-452

 received in 2012-04-26, accepted in 2012-10-01,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Oh et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]IARC: IARC monographs on the evaluation of carcinogenic risks to humans, Volume 59, Hepatitis viruses. Lyon: International Agency for Research on Cancer; 1994.
• [2]IARC: IARC monographs on the evaluation of carcinogenic risks to humans, Volume 100B, Biological agents. Lyon: International Agency for Research on Cancer; 2011.
• [3]Parkin DM: The global health burden of infection-associated cancers in the year 2002. Int J Cancer 2006, 118(12):3030-3044.
• [4]Bruno S, Crosignani A, Maisonneuve P, Rossi S, Silini E, Mondelli MU: Hepatitis C virus genotype 1b as a major risk factor associated with hepatocellular carcinoma in patients with cirrhosis: a seventeen-year prospective cohort study. Hepatology 2007, 46(5):1350-1356.
• [5]Cho LY, Yang JJ, Ko KP, Park B, Shin A, Lim MK, Oh JK, Park S, Kim YJ, Shin HR, et al.: Coinfection of hepatitis B and C viruses and risk of hepatocellular carcinoma: systematic review and meta-analysis. Int J Cancer 2011, 128(1):176-184.
• [6]Donato F, Boffetta P, Puoti M: A meta-analysis of epidemiological studies on the combined effect of hepatitis B and C virus infections in causing hepatocellular carcinoma. Int J Cancer 1998, 75(3):347-354.
• [7]Lin CL, Kao JH: The clinical implications of hepatitis B virus genotype: Recent advances. J Gastroenterol Hepatol 2011, 26(Suppl 1):123-130.
• [8]Raimondi S, Bruno S, Mondelli MU, Maisonneuve P: Hepatitis C virus genotype 1b as a risk factor for hepatocellular carcinoma development: a meta-analysis. J Hepatol 2009, 50(6):1142-1154.
• [9]Iloeje UH, Yang HI, Chen CJ: Natural history of chronic hepatitis B: what exactly has REVEAL Revealed? Liver Int 2012, 32(9):1333-1341.
• [10]Bahri O, Ezzikouri S, Alaya-Bouafif NB, Iguer F, Feydi AE, Mestiri H, Benazzouz M, Khalfallah T, Afifi R, Elkihal L, et al.: First multicenter study for risk factors for hepatocellular carcinoma development in North Africa. World J Hepatol 2011, 3(1):24-30.
• [11]Wang CH, Mo LR, Chang KK, Lin RC, Kuo JJ: A cohort study to investigate hepatocellular carcinoma risk in hepatitis C patients. Hepato-Gastroenterology 2011, 58(107–108):904-908.
• [12]Jung KW, Park S, Kong HJ, Won YJ, Lee JY, Park EC, Lee JS: Cancer statistics in Korea: incidence, mortality, survival, and prevalence in 2008. Cancer Res Treat 2011, 43(1):1-11.
• [13]Shin HR: Epidemiology of hepatitis C virus in Korea. Intervirology 2006, 49(1–2):18-22.
• [14]Korea Centers for Disease Control and Prevention: Korea Health Statistics 2009: Korea National Health and Nutrition Examination Survey (KNHANES IV-3). Seoul; 2010.
• [15]Shin A, Park S, Shin HR, Park EH, Park SK, Oh JK, Lim MK, Choi BY, Boniol M, Boffetta P: Population attributable fraction of infection-related cancers in Korea. Ann Oncol 2011, 22(6):1435-1442.
• [16]Cho JH, Yoon KH, Lee KE, Park DS, Lee YJ, Moon HB, Lee KR, Choi CS, Cho EY, Kim HC: Distribution of hepatitis B virus genotypes in Korea. Korean J Hepatol 2009, 15(2):140-147.
• [17]Kim H, Jee YM, Song BC, Shin JW, Yang SH, Mun HS, Kim HJ, Oh EJ, Yoon JH, Kim YJ, et al.: Molecular epidemiology of hepatitis B virus (HBV) genotypes and serotypes in patients with chronic HBV infection in Korea. Intervirology 2007, 50(1):52-57.
• [18]Song BC, Cui XJ, Kim H: Hepatitis B virus genotypes in Korea: an endemic area of hepatitis B virus infection. Intervirology 2005, 48(2–3):133-137.
• [19]Bouvard V, Baan R, Straif K, Grosse Y, Secretan B, El Ghissassi F, Benbrahim-Tallaa L, Guha N, Freeman C, Galichet L, et al.: A review of human carcinogens–Part B: biological agents. Lancet Oncol 09, 10(4):321-322.
• [20]Gwack J, Hwang SS, Ko KP, Jun JK, Park SK, Chang SH, Shin HR, Yoo KY: Fasting serum glucose and subsequent liver cancer risk in a Korean prospective cohort. J Prev Med Public Health 2007, 40(1):23-28.
• [21]Yoo KY, Shin HR, Chang SH, Lee KS, Park SK, Kang D, Lee DH: Korean Multi-center Cancer Cohort Study including a Biological Materials Bank (KMCC-I). Asian Pac J Cancer Prev 2002, 3(1):85-92.
• [22]Alcohol and Public Health: Frequently Asked Questions. http://www.cdc.gov/alcohol/faqs.htm webcite
• [23]WHO expert consultation: Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet 2004, 363(9403):157-163.
• [24]Okamoto H, Tokita H, Sakamoto M, Horikita M, Kojima M, Iizuka H, Mishiro S: Characterization of the genomic sequence of type V (or 3a) hepatitis C virus isolates and PCR primers for specific detection. J Gen Virol 1993, 74:2385-2390.
• [25]Andersson T, Alfredsson L, Kallberg H, Zdravkovic S, Ahlbom A: Calculating measures of biological interaction. Eur J Epidemiol 2005, 20(7):575-579.
• [26]Rothman KJ: The estimation of synergy or antagonism. Am J Epidemiol 1976, 103(5):506-511.
• [27]Chen CJ, Yang HI: Natural history of chronic hepatitis B REVEALed. J Gastroenterol Hepatol 2011, 26(4):628-638.
• [28]Shin HR, Lee CU, Park HJ, Seol SY, Chung JM, Choi HC, Ahn YO, Shigemastu T: Hepatitis B and C virus, Clonorchis sinensis for the risk of liver cancer: a case–control study in Pusan, Korea. Int J Epidemiol 1996, 25(5):933-940.
• [29]Ahn HS, Kim MH, Kim YS, Kim JS: A Case–control Study on Association Between Hepatocellular Carcinoma and Infection of Hepatitis B and Hepatitis C Virus. Korean J Prev Med 1997, 30(1):1-16.
• [30]Huh K, Lee JK, Choi SY, Hong SI, Lee DS: A Study on the Prevalence of HBsAg and Anti-HCV in Patients with Hepatocellular Carcinoma: Comparative Study with Healthy Blood Donors. Korean J Clin Pathol 1998, 18(3):458-463.
• [31]Pham ST, Bull RA, Bennett JM, Rawlinson WD, Dore GJ, Lloyd AR, White PA: Frequent multiple hepatitis C virus infections among injection drug users in a prison setting. Hepatology 2010, 52(5):1564-1572.
• [32]Qian KP, Natov SN, Pereira BJ, Lau JY: Hepatitis C virus mixed genotype infection in patients on haemodialysis. J Viral Hepat 2000, 7(2):153-160.
• [33]Yang HI, Yeh SH, Chen PJ, Iloeje UH, Jen CL, Su J, Wang LY, Lu SN, You SL, Chen DS, et al.: Associations between hepatitis B virus genotype and mutants and the risk of hepatocellular carcinoma. J Natl Cancer Inst 2008, 100(16):1134-1143.
• [34]Tanaka K, Tsuji I, Wakai K, Nagata C, Mizoue T, Inoue M, Tsugane S: Alcohol drinking and liver cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population. Jpn J Clin Oncol 2008, 38(12):816-838.
• [35]IARC: IARC monographs on the evaluation of carcinogenic risks to humans, Volume 96, Alcohol Consumption and Ethyl Carbamate. Lyon: International Agency for Research on Cancer; 2010.
• [36]IARC: IARC monographs on the evaluation of carcinogenic risks to humans, Volume 83, Tobacco smoke and involuntary smoking. Lyon: International Agency for Research on Cancer; 2004.
• [37]Fujita Y, Shibata A, Ogimoto I, Kurozawa Y, Nose T, Yoshimura T, Suzuki H, Iwai N, Sakata R, Ichikawa S, et al.: The effect of interaction between hepatitis C virus and cigarette smoking on the risk of hepatocellular carcinoma. Br J Cancer 2006, 94(5):737-739.
• [38]Hassan MM, Spitz MR, Thomas MB, El-Deeb AS, Glover KY, Nguyen NT, Chan W, Kaseb A, Curley SA, Vauthey JN, et al.: Effect of different types of smoking and synergism with hepatitis C virus on risk of hepatocellular carcinoma in American men and women: case–control study. Int J Cancer 2008, 123(8):1883-1891.
• [39]Marrero JA, Fontana RJ, Fu S, Conjeevaram HS, Su GL, Lok AS: Alcohol, tobacco and obesity are synergistic risk factors for hepatocellular carcinoma. J Hepatol 2005, 42(2):218-224.
• [40]Hassan MM, Hwang LY, Hatten CJ, Swaim M, Li D, Abbruzzese JL, Beasley P, Patt YZ: Risk factors for hepatocellular carcinoma: synergism of alcohol with viral hepatitis and diabetes mellitus. Hepatology 2002, 36(5):1206-1213.
• [41]Yuan JM, Govindarajan S, Arakawa K, Yu MC: Synergism of alcohol, diabetes, and viral hepatitis on the risk of hepatocellular carcinoma in blacks and whites in the U.S. Cancer 2004, 101(5):1009-1017.
• [42]Chen CL, Yang HI, Yang WS, Liu CJ, Chen PJ, You SL, Wang LY, Sun CA, Lu SN, Chen DS, et al.: Metabolic factors and risk of hepatocellular carcinoma by chronic hepatitis B/C infection: a follow-up study in Taiwan. Gastroenterology 2008, 135(1):111-121.
• [43]Ohki T, Tateishi R, Sato T, Masuzaki R, Imamura J, Goto T, Yamashiki N, Yoshida H, Kanai F, Kato N, et al.: Obesity is an independent risk factor for hepatocellular carcinoma development in chronic hepatitis C patients. Clin Gastroenterol Hepatol 2008, 6(4):459-464.
• [44]Polesel J, Zucchetto A, Montella M, Dal Maso L, Crispo A, La Vecchia C, Serraino D, Franceschi S, Talamini R: The impact of obesity and diabetes mellitus on the risk of hepatocellular carcinoma. Ann Oncol 2009, 20(2):353-357.
• [45]Jee SH, Ohrr H, Sull JW, Samet JM: Cigarette smoking, alcohol drinking, hepatitis B, and risk for hepatocellular carcinoma in Korea. J Natl Cancer Inst 2004, 96(24):1851-1856.
• [46]Kato N, Yokosuka O, Omata M, Hosoda K, Ohto M: Detection of hepatitis C virus ribonucleic acid in the serum by amplification with polymerase chain reaction. J Clin Invest 1990, 86(5):1764-1767.
• [47]Kasahara A, Hayashi N, Mochizuki K, Takayanagi M, Yoshioka K, Kakumu S, Iijima A, Urushihara A, Kiyosawa K, Okuda M, et al.: Risk factors for hepatocellular carcinoma and its incidence after interferon treatment in patients with chronic hepatitis C. Hepatology 1998, 27(5):1394-1402.
• [48]Song EY, Yun YM, Park MH, Seo DH: Prevalence of occult hepatitis B virus infection in a general adult population in Korea. Intervirology 2009, 52(2):57-62.
• [49]Allain JP: Occult hepatitis B virus infection: implications in transfusion. Vox Sang 2004, 86(2):83-91.
• [50]Torbenson M, Thomas DL: Occult hepatitis B. Lancet Infect Dis 2002, 2(8):479-486.
• [51]Lee MS, Kim DH, Kim H, Lee HS, Kim CY, Park TS, Yoo KY, Park BJ, Ahn YO: Hepatitis B vaccination and reduced risk of primary liver cancer among male adults: a cohort study in Korea. Int J Epidemiol 1998, 27(2):316-319.
• [52]Yoo KY, Heon K, Lee MS, Park BJ, Ahn YO, Lee HS, Kim CY, Park TS: A reconstructed cohort study on the hepatitis B virus infection as a risk factor of liver cancer in Korea. J Korean Med Sci 1991, 6(4):319-324.