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Epidemiology and Pathomechanisms

Hepatocellular Carcinoma – Epidemiological Trends and Risk Factors

Schütte K. · Bornschein J. · Malfertheiner P.

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Department of Gastroenterology, Hepatology and Infectious Diseases, Otto von Guericke University, Magdeburg, Germany

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Dig Dis 2009;27:80–92

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Article / Publication Details

First-Page Preview
Abstract of Epidemiology and Pathomechanisms

Published online: June 22, 2009
Issue release date: June 2009

Number of Print Pages: 13
Number of Figures: 3
Number of Tables: 1

ISSN: 0257-2753 (Print)
eISSN: 1421-9875 (Online)

For additional information: https://www.karger.com/DDI

Abstract

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide with about 600,000 patients dying from the disease annually. In 70–90%, HCC develops on the background of chronic liver cirrhosis or inflammation. Risk factors and etiologies vary among geographical regions. In regions with a high incidence the majority of cases are related to HBV and HCV hepatitis. In developed countries, in addition to virus-related HCC, high consumption of alcohol as well as non-alcoholic fatty liver disease often in the context of metabolic syndromes are the prevalent causes. Improvement in clinical management of patients with liver cirrhosis and the control of related complications are the key for the rising incidence of HCC. This review gives an overview on epidemiological trends and risk factors and their mechanisms involved in the hepatocarcinogenesis. Knowledge of these factors will help to improve current concepts for prevention, screening and treatment of this disease.

© 2009 S. Karger AG, Basel


References

  1. El-Serag HB, Rudolph KL: Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 2007;132:2557–2576.
  2. Parkin DM, Bray F, Ferlay J, Pisani P: Global cancer statistics, 2002. CA Cancer J Clin 2005;55:74–108.
  3. McGlynn KA, Tsao L, Hsing AW, Devesa SS, Fraumeni J: International trends and patterns of primary liver cancer. Int J Cancer 2001;94:290–296.
  4. Röcken C, Carl-McGrath S: Pathology and pathogenesis of hepatocellular carcinoma. Dig Dis 2001;19:269–278.
  5. Moller H, Mellemgaard A, Lindvig K, Olsen JH: Obesity and cancer risk: a Danish record-linkage study. Eur J Cancer 1994;30A:344–350.
  6. Chang MH, Chen CJ, Lai MS, Hsu HM, Wu TC, Kong MS, Liang DC, Shau WY, Chen DS: Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. N Engl J Med 1997;336:1855–1859.
  7. Armstrong GL, Alter MJ, McQuillan GM, Margolis HS: The past incidence of hepatitis C virus infection: implications for the future burden of chronic liver disease in the United States. Hepatology 2000;31:777–782.
  8. Wong JB, McQuillan GM, McHutchison JG, Poynard T: Estimating future hepatitis C morbidity, mortality, and costs in the United States. Am J Public Health 2000;90:1562–1569.
  9. Yoshizawa H: Hepatocellular carcinoma associated with hepatitis C virus infection in Japan: projection to other countries in the foreseeable future. Oncology 2002;62 (suppl 1):8–17.
  10. Fattovich G, Giustina G, Schalm SW, Hadziyannis S, Sanchez-Tapias J, Almasio P, Christensen E, Krogsgaard K, Degos F, De Moura MC, Solinas A, Noventa F, Realdi G, Alberti A, Quero C, Savvas S, Mas A, Craxi A, Olsen JF: Occurrence of hepatocellular carcinoma and decompensation in Western European patients with cirrhosis type B. Hepatology 1995;21:77–82.
  11. Fattovich G, Stroffolini T, Zagni I, Donato F: Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology 2004;127:S35–S50.
  12. Qian GS, Ross RK, Yu MC, Yuan JM, Gao YT, Henderson BE, Wogan GN, Groopman JD: A follow-up study of urinary markers of aflatoxin exposure and liver cancer risk in Shanghai, People’s Republic of China. Cancer Epidemiol Biomarkers Prev 1994;3:3–10.
  13. McGlynn KA, Rosvold EA, Lustbader ED, Hu Y, Clapper ML, Zhou T, Wild CP, Xia XL, Baffoe-Bonnie A, Ofori-Adjei D, Chen GC, London WT, Shen FM, Buetow KH: Susceptibility to hepatocellular carcinoma is associated with genetic variation in the enzymatic detoxification of aflatoxin B1. Proc Natl Acad Sci USA 1995;92:2384–2387.
  14. Sun Z, Lu P, Gail MH, Pee D, Zhang Q, Ming L, Wang J, Wu V, Liu G, Wu Y, Zhu Y: Increased risk of hepatocellular carcinoma in male hepatitis B surface antigen carriers with chronic hepatitis who have detectable urinary aflatoxin metabolite M1. Hepatology 1999;30:379–383.
  15. Rudolph KL, Chang S, Millard M, Schreiber-Agus N, DePinho RA: Inhibition of experimental liver cirrhosis in mice by telomerase gene delivery. Science 2000;287:1253–1258.
  16. Kao JH, Chen DS: Changing disease burden of hepatocellular carcinoma in the Far East and Southeast Asia. Liver Int 2005;25:696–703.
  17. Fattovich G, Giustina G, Degos F, Tremolada F, Diodati G, Almasio P, Nevens F, Solinas A, Mura D, Brouwer JT, Thomas H, Njapoum C, Casarin C, Bonetti P, Fuschi P, Basho J, Tocco A, Bhalla A, Galassini R, Noventa F, Schalm SW, Realdi G: Morbidity and mortality in compensated cirrhosis type C: a retrospective follow-up study of 384 patients. Gastroenterology 1997;112:463–472.
  18. Evert M, Dombrowski F: Hepatocellular carcinoma in the non-cirrhotic liver. Pathologe 2008;29:47–52.
  19. Kumar M, Kumar R, Hissar SS, Saraswat MK, Sharma BC, Sakhuja P, Sarin SK: Risk factors analysis for hepatocellular carcinoma in patients with and without cirrhosis: a case-control study of 213 hepatocellular carcinoma patients from India. J Gastroenterol Hepatol 2007;22:1104–1111.
  20. Schuppan D, Afdhal NH: Liver cirrhosis. Lancet 2008;371:838–851.
  21. Bosch FX, Ribes J, Díaz M, Cléries R: Primary liver cancer: worldwide incidence and trends. Gastroenterology 2004;127:S5–S16.
  22. Bosch F, Ribes J: The epidemiology of primary liver cancer: global epidemiology; in Tabor E (ed): Viruses and Liver Cancer, ed 1. Amsterdam, Elsevier, 2002, pp 1–16.
  23. Fattovich G, Giustina G, Realdi G, Corrocher R, Schalm SW: Long-term outcome of hepatitis B e antigen-positive patients with compensated cirrhosis treated with interferon-α. Hepatology 1997;26:1338–1342.
  24. Liu CJ, Chen BF, Chen PJ, Lai MY, Huang WL, Kao JH, Chen DS: Role of hepatitis B viral load and basal core promoter mutation in hepatocellular carcinoma in hepatitis B carriers. J Infect Dis 2006;193:1258–1265.
  25. Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, Huang GT, Iloeje UH: Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA 2006;295:65–73.
  26. Yuen MF, Tanaka Y, Fong DYT, Fung J, Wong DKH, Yuen JCH, But DYK, Chan AOO, Wong BCY, Mizokami M, Lai CL: Independent risk factors and predictive score for the development of hepatocellular carcinoma in chronic hepatitis B. J Hepatol 2009;50:80–88.
  27. Yang HI, Lu SN, Liaw YF, You SL, Sun CA, Wang LY, Hsiao CK, Chen PJ, Chen DS, Chen CJ: Hepatitis B e antigen and the risk of hepatocellular carcinoma. N Engl J Med 2002;347:168–174.
  28. Yang YF, Zhao W, Zhong YD, Xia HM, Shen L, Zhang N: Interferon therapy in chronic hepatitis B reduces progression to cirrhosis and hepatocellular carcinoma: a meta-analysis. J Viral Hepat 2009;16:265–271.
  29. Lin SM, Yu ML, Lee CM, Chien RN, Sheen IS, Chu CM, Liaw YF: Interferon therapy in HBeAg-positive chronic hepatitis reduces progression to cirrhosis and hepatocellular carcinoma. J Hepatol 2007;46:45–52.
  30. Liaw YF: Natural history of chronic hepatitis B virus infection and long-term outcome under treatment. Liver Int 2009;29:100–107.
  31. Liu CJ, Kao JH, Chen DS: Therapeutic implications of hepatitis B virus genotypes. Liver Int 2005;25:1097–1107.
  32. Kao JH: Hepatitis B virus genotypes and hepatocellular carcinoma in Taiwan. Intervirology 2003;46:400–407.
  33. Chan HLY, Hui AY, Wong ML, Tse AML, Hung LCT, Wong VWS, Sung JJY: Genotype C hepatitis B virus infection is associated with an increased risk of hepatocellular carcinoma. Gut 2004;53:1494–1498.
  34. Chan HLY, Tse CH, Mo F, Koh J, Wong VWS, Wong GLH, Chan SL, Yeo W, Sung JJY, Mok TSK: High viral load and hepatitis B virus subgenotype Ce are associated with increased risk of hepatocellular carcinoma. J Clin Oncol 2008;26:177–182.
  35. Yang HI, Yeh SH, Chen PJ, Iloeje UH, Jen CL, Su J, Wang LY, Lu SN, You SL, Chen DS, Liaw YF, Chen CJ: Associations between hepatitis B virus genotype and mutants and the risk of hepatocellular carcinoma. J Natl Cancer Inst 2008;100:1134–1143.
  36. Yuen MF, Tanaka Y, Shinkai N, Poon RT, But DYK, Fong DYT, Fung J, Wong DKH, Yuen JCH, Mizokami M, Lai CL: Risk for hepatocellular carcinoma with respect to hepatitis B virus genotypes B/C, specific mutations of enhancer II/core promoter/precore regions and HBV DNA levels. Gut 2008;57:98–102.
  37. Kao JH: Hepatitis B viral genotypes: clinical relevance and molecular characteristics. J Gastroenterol Hepatol 2002;17:643–650.
  38. Gomaa AI, Khan SA, Toledano MB, Waked I, Taylor-Robinson SD: Hepatocellular carcinoma: epidemiology, risk factors and pathogenesis. World J Gastroenterol 2008;14:4300–4308.
  39. Fattovich G, Giustina G, Christensen E, Pantalena M, Zagni I, Realdi G, Schalm SW: Influence of hepatitis delta virus infection on morbidity and mortality in compensated cirrhosis type B. Gut 2000;46:420–426.
  40. Tamura I, Kurimura O, Koda T, Ichimura H, Katayama S, Kurimura T, Inaba Y: Risk of liver cirrhosis and hepatocellular carcinoma in subjects with hepatitis B and delta virus infection: a study from Kure, Japan. J Gastroenterol Hepatol 1993;8:433–436.
  41. Donato F, Tagger A, Gelatti U, Parrinello G, Boffetta P, Albertini A, Decarli A, Trevisi P, Ribero ML, Martelli C, Porru S, Nardi G: Alcohol and hepatocellular carcinoma: the effect of lifetime intake and hepatitis virus infections in men and women. Am J Epidemiol 2002;155:323–331.
  42. El-Serag HB: Hepatocellular carcinoma and hepatitis C in the United States. Hepatology 2002;36:S74–S83.
  43. Ikeda K, Saitoh S, Arase Y, Chayama K, Suzuki Y, Kobayashi M, Tsubota A, Kobayashi M, Nakamura I, Murashima N, Kumada H, Kawanishi M: Effect of interferon therapy on hepatocellular carcinogenesis in patients with chronic hepatitis type C: a long-term observation study of 1,643 patients using statistical bias correction with proportional hazard analysis. Hepatology 1999;29:1124–1130.
  44. Bruno S, Battezzati PM, Bellati G, Manzin A, Maggioni M, Crosignani A, Borzio M, Solforosi L, Morabito A, Ideo G, Podda M: Long-term beneficial effects in sustained responders to interferon-α therapy for chronic hepatitis C. J Hepatol 2001;34:748–755.
  45. Goodgame B, Shaheen NJ, Galanko J, El-Serag HB: The risk of end-stage liver disease and hepatocellular carcinoma among persons infected with hepatitis C virus: publication bias? Am J Gastroenterol 2003;98:2535–2542.
  46. Seeff LB: The history of the ‘natural history’ of hepatitis C (1968–2009). Liver Int 2009;29:89–99.
  47. Seeff LB: Natural history of hepatitis C. Hepatology 1997;26:21S–28S.
  48. Leone N, Rizzetto M: Natural history of hepatitis C virus infection: from chronic hepatitis to cirrhosis, to hepatocellular carcinoma. Minerva Gastroenterol Dietol 2005;51:31–46.
  49. Amarapurkar D: Natural history of hepatitis C virus infection. J Gastroenterol Hepatol 2000;15:E105–E110.
  50. Poynard T, Bedossa P, Opolon P: Natural history of liver fibrosis progression in patients with chronic hepatitis C. Lancet 1997;349:825–832.
  51. Freeman AJ, Dore GJ, Law MG, Thorpe M, Von Overbeck J, Lloyd AR, Marinos G, Kaldor JM: Estimating progression to cirrhosis in chronic hepatitis C virus infection. Hepatology 2001;34:809–816.
  52. Lok AS, Seeff LB, Morgan TR, di Bisceglie AM, Sterling RK, Curto TM, Everson GT, Lindsay KL, Lee WM, Bonkovsky HL, Dienstag JL, Ghany MG, Morishima C, Goodman ZD: Incidence of hepatocellular carcinoma and associated risk factors in hepatitis C-related advanced liver disease. Gastroenterology 2009;136:138–148.
  53. Yoshida H, Shiratori Y, Moriyama M, Arakawa Y, Ide T, Sata M, Inoue O, Yano M, Tanaka M, Fujiyama S, Nishiguchi S, Kuroki T, Imazeki F, Yokosuka O, Kinoyama S, Yamada G, Omata M: Interferon therapy reduces the risk for hepatocellular carcinoma: national surveillance program of cirrhotic and noncirrhotic patients with chronic hepatitis C in Japan. Ann Intern Med 1999;131:174–181.
  54. Liang TJ, Heller T: Pathogenesis of hepatitis C-associated hepatocellular carcinoma. Gas- troenterology 2004;127:S62–S71.
  55. Lauer GM, Walker BD: Hepatitis C virus infection. N Engl J Med 2001;345:41–52.
  56. Sung VM, Shimodaira S, Doughty AL, Picchio GR, Can H, Yen TS, Lindsay KL, Levine AM, Lai MM: Establishment of B-cell lymphoma cell lines persistently infected with hepatitis C virus in vivo and in vitro: the apoptotic effects of virus infection. J Virol 2003;77:2134–2146.
  57. 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;75:347–354.
  58. Stroffolini T, Almasio PL, Persico M, Bollani S, Benvegnù L, Di Costanzo G, Pastore G, Aghemo A, Stornaiuolo G, Mangia A, Andreone P, Stanzione M, Mazzella G, Saracco G, Del Poggio P, Bruno S: Lack of correlation between serum anti-HB core detectability and hepatocellular carcinoma in patients with HCV-related cirrhosis. Am J Gastroenterol 2008;103:1966–1972.
  59. Morgan TR, Mandayam S, Jamal MM: Alcohol and hepatocellular carcinoma. Gastroenterology 2004;127:S87–S96.
  60. Seitz HK, Stickel F: Risk factors and mechanisms of hepatocarcinogenesis with special emphasis on alcohol and oxidative stress. Biol Chem 2006;387:349–360.
  61. Prior P: Long-term cancer risk in alcoholism. Alcohol Alcohol 1988;23:163–171.
  62. Becker U, Deis A, Sørensen TIA, Grønbæk M, Borch-Johnsen K, Müller CF, Schnohr P, Jensen G: Prediction of risk of liver disease by alcohol intake, sex, and age: a prospective population study. Hepatology 1996;23:1025–1029.
  63. Inoue H, Seitz HK: Viruses and alcohol in the pathogenesis of primary hepatic carcinoma. Eur J Cancer Prev 2001;10:107–110.
  64. Homann N, Stickel F, König IR, Jacobs A, Junghanns K, Benesova M, Schuppan D, Himsel S, Zuber-Jerger I, Hellerbrand C, Ludwig D, Caselmann WH, Seitz HK: Alcohol dehydrogenase 1C*1 allele is a genetic marker for alcohol-associated cancer in heavy drinkers. Int J Cancer 2006;118:1998–2002.
  65. Seitz HK, Osswald BR: Effect of ethanol on procarcinogen activation; in Watson RR (ed): Alcohol and the Gastrointestinal Tract. Boca Raton, CRC Press, 1992, pp 55–72.
  66. Chung BH, Mitchell SH, Zhang JS, Young CYF: Effects of docosahexaenoic acid and eicosapentaenoic acid on androgen-mediated cell growth and gene expression in LNCaP prostate cancer cells. Carcinogenesis 2001;22:1201–1206.
  67. Chung J, Liu C, Smith DE, Seitz HK, Russell RM, Wang XD: Restoration of retinoic acid concentration suppresses ethanol-enhanced c-Jun expression and hepatocyte proliferation in rat liver. Carcinogenesis 2001;22:1213–1219.
  68. Wang XD, Liu C, Chung J, Stickel F, Seitz HK, Russell RM: Chronic alcohol intake reduces retinoic acid concentration and enhances AP-1 (c-Jun and c-Fos) expression in rat liver. Hepatology 1998;28:744–750.
  69. Liu C, Russell RM, Seitz HK, Wang XD: Ethanol enhances retinoic acid metabolism into polar metabolites in rat liver via induction of cytochrome P4502E1. Gastroenterology 2001;120:179–189.
  70. Ohnishi K, Iida S, Iwama S: The effect of chronic habitual alcohol intake on the development of liver cirrhosis and hepatocellular carcinoma: relation to hepatitis B surface antigen carriage. Cancer 1982;49:672–677.
  71. Stickel F, Schuppan D, Hahn EG, Seitz HK: Cocarcinogenic effects of alcohol in hepatocarcinogenesis. Gut 2002;51:132–139.
  72. Craddock VM: Metabolism of ethanol and higher alcohols present in alcoholic drinks and their corresponding aldehydes in subcellular components of rat esophageal mucosa, and relevance for esophageal cancer in men; in Palmer TN (ed): Alcoholism: a Molecular Perspective. New York, Plenum Press, 1991, pp 297–301.
  73. Kuper H, Tzonou A, Kaklamani E, Hsieh CC, Lagiou P, Adami HO, Trichopoulos D, Stuver SO: Tobacco smoking, alcohol consumption and their interaction in the causation of hepatocellular carcinoma. Int J Cancer 2000;85:498–502.
  74. Donato F, Gelatti U, Limina RM, Fattovich G: Southern Europe as an example of interaction between various environmental factors: a systematic review of the epidemiologic evidence. Oncogene 2006;25:3756–3770.
  75. Chiesa R, Donato F, Tagger A, Favret M, Ribero ML, Nardi G, Gelatti U, Bucella E, Tomasi E, Portolani N, Bonetti M, Bettini L, Pelizzari G, Salmi A, Savio A, Garatti M, Callea F: Etiology of hepatocellular carcinoma in Italian patients with and without cirrhosis. Cancer Epidemiol Biomarkers Prev 2000;9:213–216.
  76. Marrero JA, Fontana RJ, Su GL, Conjeevaram HS, Emick DM, Lok AS: NAFLD may be a common underlying liver disease in patients with hepatocellular carcinoma in the United States. Hepatology 2002;36:1349–1354.
  77. Bugianesi E, Leone N, Vanni E, Marchesini G, Brunello F, Carucci P, Musso A, De Paolis P, Capussotti L, Salizzoni M, Rizzetto M: Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology 2002;123:134–140.
  78. Takamatsu S, Noguchi N, Kudoh A, Nakamura N, Kawamura T, Teramoto K, Igari T, Arii S: Influence of risk factors for metabolic syndrome and non-alcoholic fatty liver disease on the progression and prognosis of hepatocellular carcinoma. Hepatogastroenterology 2008;55:609–614.
  79. Regimbeau JM, Colombat M, Mognol P, Durand F, Abdalla E, Degott C, Degos F, Farges O, Belghiti J: Obesity and diabetes as a risk factor for hepatocellular carcinoma. Liver Transpl 2004;10:S69–S73.
  80. Neuschwander-Tetri BA: Nonalcoholic steatohepatitis and the metabolic syndrome. Am J Med Sci 2005;330:326–335.
  81. Huang HL, Lin WY, Lee LT, Wang HH, Lee WJ, Huang KC: Metabolic syndrome is related to nonalcoholic steatohepatitis in severely obese subjects. Obes Surg 2007;17:1457–1463.
  82. Gholam PM, Flancbaum L, MacHan JT, Charney DA, Kotler DP: Nonalcoholic fatty liver disease in severely obese subjects. Am J Gastroenterol 2007;102:399–408.
  83. Ekstedt M, Franzén LE, Mathiesen UL, Thorelius L, Holmqvist M, Bodemar G, Kechagias S: Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 2006;44:865–873.
  84. Byrne CD, Olufadi R, Bruce KD, Cagampang FR, Ahmed MH: Metabolic disturbances in non-alcoholic fatty liver disease. Clin Sci (Lond) 2009;116:539–564.
  85. Guzman G, Brunt EM, Petrovic LM, Chejfec G, Layden TJ, Cotler SJ: Does nonalcoholic fatty liver disease predispose patients to hepatocellular carcinoma in the absence of cirrhosis? Arch Pathol Lab Med 2008;132:1761–1766.
  86. Caldwell SH, Crespo DM, Kang HS, Al-Osaimi AMS: Obesity and hepatocellular carcinoma. Gastroenterology 2004;127:S97–S103.
  87. Mori S, Yamasaki T, Sakaida I, Takami T, Sakaguchi E, Kimura T, Kurokawa F, Maeyama S, Okita K: Hepatocellular carcinoma with nonalcoholic steatohepatitis. J Gastroenterol 2004;39:391–396.
  88. Paradis V, Zalinski S, Chelbi E, Guedj N, Degos F, Vilgrain V, Bedossa P, Belghiti J: Hepatocellular carcinomas in patients with metabolic syndrome often develop without significant liver fibrosis: a pathological analysis. Hepatology 2009;49:851–859.
  89. Davila JA, Morgan RO, Shaib Y, McGlynn KA, El-Serag HB: Diabetes increases the risk of hepatocellular carcinoma in the United States: a population-based case-control study. Gut 2005;54:533–539.
  90. El-Serag HB, Richardson PA, Everhart JE: The role of diabetes in hepatocellular carcinoma: a case-control study among United States Veterans. Am J Gastroenterol 2001;96:2462–2467.
  91. Donadon V, Balbi M, Casarin P, Vario A, Alberti A: Association between hepatocellular carcinoma and type 2 diabetes mellitus in Italy: potential role of insulin. World J Gastroenterol 2008;14:5695–5700.
  92. 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;20:353–357.
  93. El-Serag HB, Hampel H, Javadi F: The association between diabetes and hepatocellular carcinoma: a systematic review of epidemiologic evidence. Clin Gastroenterol Hepatol 2006;4:369–380.
  94. Torisu Y, Ikeda K, Kobayashi M, Hosaka T, Sezaki H, Akuta N, Kawamura T, Yatsuji H, Suzuki F, Suzuki Y, Arase Y, Kumada H: Diabetes mellitus increases the risk of hepatocarcinogenesis in patients with alcoholic cirrhosis: a preliminary report. Hepatol Res 2007;37:517–523.
  95. N’Kontchou G, Paries J, Htar MTT, Ganne-Carrie N, Costentin L, Grando-Lemaire V, Trinchet J, Beaugrand M: Risk factors for hepatocellular carcinoma in patients with alcoholic or viral c cirrhosis. Clin Gastroenterol Hepatol 2006;4:1062–1068.
  96. Chen CL, Yang HI, Yang WS, Liu CJ, Chen PJ, You SL, Wang LY, Sun CA, Lu SN, Chen DS, Chen CJ: Metabolic factors and risk of hepatocellular carcinoma by chronic hepatitis B/C infection: a follow-up study in Taiwan. Gastroenterology 2008;135:111–121.
  97. Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ: Overweight, obesity, and mortality from cancer in a prospectively studied cohort of US adults. N Engl J Med 2003;348:1625–1638.
  98. Ohki T, Tateishi R, Sato T, Masuzaki R, Imamura J, Goto T, Yamashiki N, Yoshida H, Kanai F, Kato N, Shiina S, Yoshida H, Kawabe T, Omata M: Obesity is an independent risk factor for hepatocellular carcinoma development in chronic hepatitis C patients. Clin Gastroenterol Hepatol 2008;6:459–464.
  99. 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;42:218–224.
  100. Nair S, Mason A, Eason J, Loss G, Perrillo RP: Is obesity an independent risk factor for hepatocellular carcinoma in cirrhosis? Hepatology 2002;36:150–155.
  101. Adams LA, Sanderson S, Lindor KD, Angulo P: The histological course of nonalcoholic fatty liver disease: a longitudinal study of 103 patients with sequential liver biopsies. J Hepatol 2005;42:132–138.
  102. Teufel A, Galle PR, Kanzler S: Update on autoimmune hepatitis. World J Gastroenterol 2009;15:1035–1041.
  103. Watanabe TF, Soga KF, Hirono HF, Hasegawa KF, Shibasaki KF, Kawai HF, Aoyagi Y: Features of hepatocellular carcinoma in cases with autoimmune hepatitis and primary biliary cirrhosis. World J Gastroenterol 2009;15:231–239.
  104. Yeoman AD, Al-Chalabi T, Karani JB, Quaglia A, Devlin J, Mieli-Vergani G, Bomford A, O’Grady JG, Harrison PM, Heneghan MA: Evaluation of risk factors in the development of hepatocellular carcinoma in autoimmune hepatitis: implications for follow-up and screening. Hepatology 2008;48:863–870.
  105. Werner M, Almer S, Prytz H, Lindgren S, Wallerstedt S, Björnsson E, Bergquist A, Sandberg-Gertzén H, Hultcrantz R, Sangfelt P, Weiland O, Danielsson A: Hepatic and extrahepatic malignancies in autoimmune hepatitis. A long-term follow-up in 473 Swedish patients. J Hepatol 2009;50:388–393.
  106. Montano-Loza AJ, Carpenter HA, Czaja AJ: Predictive factors for hepatocellular carcinoma in type 1 autoimmune hepatitis. Am J Gastroenterol 2008;103:1944–1951.
  107. Kew MC: Hepatic iron overload and hepatocellular carcinoma. Cancer Lett 2008, Dec 9 (Epub ahead of print).
  108. Kowdley KV: Iron, hemochromatosis, and hepatocellular carcinoma. Gastroenterology 2004;127:S79–S86.
  109. Asare GA, Paterson AC, Kew MC, Khan S, Mossanda KS: Iron-free neoplastic nodules and hepatocellular carcinoma without cirrhosis in Wistar rats fed a diet high in iron. J Pathol 2006;208:82–90.
  110. Asare GA, Bronz M, Naidoo V, Kew MC: Synergistic interaction between excess hepatic iron and alcohol ingestion in hepatic mutagenesis. Toxicology 2008;254:11–18.
  111. Blanc JF, Ledinghen VD, Bernard PH, Verneuil HD, Winnock M, Le Bail B, Carles J, Saric J, Balabaud C, Bioulac-Sage P: Increased incidence of HFE C282Y mutations in patients with iron overload and hepatocellular carcinoma developed in non-cirrhotic liver. J Hepatol 2000;32:805–811.
  112. Burke W, Imperatore G, McDonnell SM, Baron RC, Khoury MJ: Contribution of different HFE genotypes to iron overload disease: a pooled analysis. Gen Med 2000;2:271–277.
  113. El-Serag HB, Rudolph KL: Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 2007;132:2557–2576.
  114. Fargion S, Stazi MA, Fracanzani AL, Mattioli M, Sampietro M, Tavazzi D, Bertelli C, Patriarca V, Mariani C, Fiorelli G: Mutations in the HFE gene and their interaction with exogenous risk factors in hepatocellular carcinoma. Blood Cells Mol Dis 2001;27:505–511.
  115. Hellerbrand C, Pöppl A, Hartmann A, Schölmerich J, Lock G: HFE C282Y heterozygosity in hepatocellular carcinoma: evidence for an increased prevalence. Clin Gastroenterol Hepatol 2003;1:279–284.
  116. Boige V, Castéra L, De Roux N, Ganne-Carrié N, Ducot B, Pelletier G, Beaugrand M, Buffet C: Lack of association between HFE gene mutations and hepatocellular carcinoma in patients with cirrhosis. Gut 2003;52:1178–1181.
  117. Lauret E, Rodríguez M, González S, Linares A, López-Vázquez A, Martínez-Borra J, Rodrigo L, López-Larrea C: HFE gene mutations in alcoholic and virus-related cirrhotic patients with hepatocellular carcinoma. Am J Gastroenterol 2002;97:1016–1021.
  118. Nahon P, Sutton A, Rufat P, Ziol M, Thabut G, Schischmanoff P, Vidaud D, Charnaux N, Couvert P, Ganne-Carrie N, Trinchet J, Gattegno L, Beaugrand M: Liver iron, HFE gene mutations, and hepatocellular carcinoma occurrence in patients with cirrhosis. Gastroenterology 2008;134:102–110.
  119. Rosen HR: Liver disease associated with α1-antitrypsin deficiency. Clin Liver Dis 1998;2:175–185.
  120. Fairbanks KD, Tavill AS: Liver disease in α1-antitrypsin deficiency: a review. Am J Gastroenterol 2008;103:2136–2141.
  121. Rakela J, Goldschmiedt M, Ludwig J: Late manifestation of chronic liver disease in adults with α1-antitrypsin deficiency. Dig Dis Sci 1987;32:1358–1362.
  122. Bowlus CL, Willner I, Zern MA: Factors associated with advanced liver disease in adults with α1-antitrypsin deficiency. Clin Gastroenterol Hepatol 2005;3:390–396.
  123. Rudnick DA, Perlmutter DH: α1-Antitrypsin deficiency: a new paradigm for hepatocellular carcinoma in genetic liver disease. Hepatology 2005;42:514–521.
  124. Kok KF, Wahab PJ, Houwen RHJ, Drenth JPH, de Man RA, van Hoek B, Meijer JWR, Willekens FLA, de Vries RA: Heterozygous α1-antitrypsin deficiency as a cofactor in the development of chronic liver disease. Neth J Med 2007;65:160–166.
  125. Kuper H, Tzonou A, Lagiou P, Mucci LA, Trichopoulos D, Stuver SO, Trichopoulou A: Diet and hepatocellular carcinoma: a case-control study in Greece. Nutr Cancer 2000;38:6–12.
  126. Polesel J, Talamini R, Montella M, Maso LD, Crovatto M, Parpinel M, Izzo F, Tommasi LG, Serraino D, Vecchia CL, Franceschi S: Nutrients intake and the risk of hepatocellular carcinoma in Italy. Eur J Cancer 2007;43:2381–2387.
  127. Talamini R, Polesel J, Montella M, Dal Maso L, Crispo A, Tommasi LG, Izzo F, Crovatto M, La Vecchia C, Franceschi S: Food groups and risk of hepatocellular carcinoma: a multicenter case-control study in Italy. Int J Cancer 2006;119:2916–2921.
  128. Kuroiwa-Trzmielina J, de Conti A, Scolastici C, Pereira D, Horst MA, Purgatto E, Ong TP, Moreno FS: Chemoprevention of rat hepatocarcinogenesis with histone deacetylase inhibitors: efficacy of tributyrin, a butyric acid prodrug. Int J Cancer 2009;124:2520–2527.
  129. Chao JCJ, Chu CC: Effects of Ginkgo biloba extract on cell proliferation and cytotoxicity in human hepatocellular carcinoma cells. World J Gastroenterol 2004;10:37–41.
  130. Cadden ISH, Partovi N, Yoshida EM: Possible beneficial effects of coffee on liver disease and function. Aliment Pharmacol Ther 2007;26:1–7.
  131. Bravi F, Bosetti C, Tavani A, Bagnardi V, Gallus S, Negri E, Franceschi S, La Vecchia C: Coffee drinking and hepatocellular carcinoma risk: a meta-analysis. Hepatology 2007;46:430–435.
  132. Klatsky AL, Morton C, Udaltsova N, Friedman GD: Coffee, cirrhosis, and transaminase enzymes. Arch Intern Med 2006;166:1190–1195.
  133. Tanaka K, Tokunaga S, Kono S, Tokudome S, Akamatsu T, Moriyama T, Zakouji H: Coffee consumption and decreased serum γ-glutamyltransferase and aminotransferase activities among male alcohol drinkers. Int J Epidemiol 1998;27:438–443.
  134. Ruhl CE, Everhart JE: Coffee and tea consumption are associated with a lower incidence of chronic liver disease in the United States. Gastroenterology 2005;129:1928–1936.
  135. Larsson SC, Wolk A: Coffee consumption and risk of liver cancer: a meta-analysis. Gastroenterology 2007;132:1740–1745.
  136. Pineau P, Marchio A, Battiston C, Cordina E, Russo A, Terris B, Qin LX, Turlin B, Tang ZY, Mazzaferro V, Dejean A: Chromosome instability in human hepatocellular carcinoma depends on p53 status and aflatoxin exposure. Mutat Res Genet Toxicol Environ Mutagen 2008;653:6–13.
  137. Wu HC, Wang Q, Yang HI, Ahsan H, Tsai WY, Wang LY, Chen SY, Chen CJ, Santella RM: Aflatoxin B1 exposure, hepatitis B virus infection, and hepatocellular carcinoma in Taiwan. Cancer Epidemiol Biomarkers Prev 2009;18:846–853.
  138. Chu CH, Kleiner J, Axiotis CA, Di Bisceglie A, Nomura AMY, Stemmermann GN, Tabor E: Mutations of p53 gene in hepatocellular carcinoma: roles of hepatitis B virus and aflatoxin contamination in the diet. J Natl Cancer Inst 1992;84:1638–1641.
  139. Wu HC, Wang Q, Yang HI, Ahsan H, Tsai WY, Wang LY, Chen SY, Chen CJ, Santella RM: Urinary 15-F2t-isoprostane, aflatoxin B1 exposure and hepatitis B virus infection and hepatocellular carcinoma in Taiwan. Carcinogenesis 2008;29:971–976.
  140. Donato F, Tagger A, Gelatti V, et al: Alcohol and hepatocellular carcinoma: the effect of lifetime intake and hepatitis infections in men and women. Am J Epidemiol 2002; 155:323–331.

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Abstract of Epidemiology and Pathomechanisms

Published online: June 22, 2009
Issue release date: June 2009

Number of Print Pages: 13
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ISSN: 0257-2753 (Print)
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