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VOLUME 9 , ISSUE 1 ( January-June, 2019 ) > List of Articles

REVIEW ARTICLE

Hepatocellular Carcinoma in Asia: A Challenging Situation

Wasim Jafri, Muhammad Kamran

Keywords : Aflatoxin, Hepatitis B virus, Hepatitis C virus, Hepatocellular carcinoma, Nonalcoholic steatohepatitis

Citation Information : Jafri W, Kamran M. Hepatocellular Carcinoma in Asia: A Challenging Situation. Euroasian J Hepatogastroenterol 2019; 9 (1):27-33.

DOI: 10.5005/jp-journals-10018-1292

License: CC BY-NC 4.0

Published Online: 01-09-2019

Copyright Statement:  Copyright © 2019; The Author(s).


Abstract

Amongst the primary tumors of the liver, hepatocellular carcinoma (HCC) is the most common. It is also one of the most prevalent types of cancers in Asia. Mostly, HCC occurs on a background of chronic liver disease and liver cirrhosis; however, de novo HCCs can also arise in apparently normal looking livers on imaging. There are multiple risk factors for HCC, including hepatitis B and C infections, diabetes mellitus, alcohol, and nonalcoholic steatohepatitis. Other common risk factors which are known to be involved in the pathogenesis of HCC are obesity, food contaminated with aflatoxin and hemochromatosis. Many of these factors are commonly found in this part of the world, hence the high burden of disease. Besides these, smoking and familial predisposition to HCC also seem to have an important role to play in its development. Majority of HCC are missed at an early stage despite the emphasis on adequate screening and surveillance strategies. Therefore, most of the time these tumors are diagnosed at a fairly advanced stage, when palliative treatment is the only therapeutic option left. Hence, prevention of HCC by controlling and minimizing the possible risk factors is the need of the hour.


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  1. Stuver S, Trichopolous D. Cancer of the liver and biliary tract. In: Adami HO, Hunter D, Trichopolous D, editors. Textbook of cancer epidemiology. 2rd ed. New York: Oxford University Press; 2008. 308-332.
  2. Zhu XR, Seto WK, et al. Epidemiology of hepatocellular carcinoma in the Asia-pacific region. Gut and Liver 2016;10(3):332-339.
  3. Ferlay J, Shin HR, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010;127(2):2893-2917.
  4. Yang JD, Roberts LR. Hepatocellular carcinoma: A global view. Nat Rev Gastroenterol Hepatol 2010;7(8):448-458.
  5. IARC. Hepatitis viruses. IARC Monogr Eval Carcinog Risks Hum 1994;59.1-255.
  6. IARC. Some traditional herbal medicines, some mycotoxins, naphthalene and styrene. IARC Monogr Eval Carcinog Risks Hum 2002;82:1-556.
  7. Nisa A, Zahra N, et al. Detection of aflatoxins in rice samples. Bangladesh J Sci Ind Res 2014;49(3)189-194.
  8. Lai CL, Ratziu V, et al. Viral hepatitis B. Lancet 2003;362(9401):2089- 2094.
  9. Gomaa AI, Khan SA, et al. Hepatocellular carcinoma: epidemiology, risk factors and pathogenesis. World J Gastroenterol 2008;14(27):4300- 4308.
  10. Di Bisceglie AM. Epidemiology and clinical presentation of hepatocellular carcinoma. J Vasc Interv Radiol 2002;13(9 Pt 2):S169- S171.
  11. El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 2007;132(7):2557- 2576.
  12. Poon D, Anderson BO, et al. Management of hepatocellular carcinoma in Asia: consensus statement from the Asian Oncology Summit 2009. Lancet Oncol 2009;10(11):1111-1118.
  13. Chisari FV, Klopchin K, et al. Molecular pathogenesis of hepatocellular carcinoma in hepatitis B virus transgenic mice. Cell 1989;59(6):1145-1156.
  14. Idilman R, De Maria N, et al. Pathogenesis of hepatitis B and C-induced hepatocellular carcinoma. J Viral Hepat 1998;5(5):285-299.
  15. Montalto G, Cervello M, et al. Epidemiology, risk factors, and natural history of hepatocellular carcinoma. Ann N Y Acad Sci 2002;963:13-20.
  16. McGlynn KA, London WT. Epidemiology and natural history of hepatocellular carcinoma. Best Pract Res Clin Gastroenterol 2005;19(1):3-23.
  17. Schweitzer A, Horn J, et al. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet 2015;386(10003):1546-1555.
  18. Block TM, Mehta AS, et al. Molecular viral oncology of hepatocellular carcinoma. Oncogene 2003;22(33):5093-5107.
  19. Mori M, Hara M, et al. Prospective study of hepatitis B and C viral infections, cigarette smoking, alcohol consumption, and other factors associated with hepatocellular carcinoma risk in Japan. Am J Epidemiol 2000;151(2):131-139.
  20. Yang HI, Lu SN, et al. Hepatitis B e antigen and the risk of hepatocellular carcinoma. N Engl J Med 2002;347(3):168-174.
  21. Ming L, Thorgeirsson SS, et al. Dominant role of hepatitis B virus and cofactor role of aflatoxin in hepatocarcinogenesis in Qidong, China. Hepatology 2002;36(5):1214-1220.
  22. Chen CJ, Yang HI, et al; REVEAL-HBV Study Group. Hepatitis B virus DNA levels and outcomes in chronic hepatitis B. Hepatology 2009;49(5 Suppl):S72-S84.
  23. McMahon BJ. Natural history of chronic hepatitis B. Clin Liver Dis 2010;14(3):381-396.
  24. Tseng TC, Liu CJ, et al. High levels of hepatitis B surface antigen increase risk of hepatocellular carcinoma in patients with low HBV load. Gastroenterology 2012;142(5):1140-1149.e3.
  25. Szabo E, Lotz G, et al. Viral hepatitis: new data on hepatitis C infection. Pathol Oncol Res 2003;9(4):215–221.
  26. Mohd Hanafiah K, Groeger J, et al. Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence. Hepatology 2013;57(4):1333-1342.
  27. Lin MV, King LY, et al. Hepatitis C virus–associated cancer. Annu Rev Pathol 2015;10:345-370.
  28. Massarweh NN, El-Serag HB. Epidemiology of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma. Cancer Control 2017;24(3).
  29. Yoshida H, Shiratori Y, et al. Interferon therapy reduces the risk for hepatocellular carcinoma: national surveillance program of cirrhotic and noncirrhotic patients with chronic hepatitis C in Japan. IHIT Study Group Inhibition of Hepatocarcinogenesis by Interferon Therapy. Ann Intern Med 1999;131(3):174-181.
  30. Chung RT, Baumert TF. Curing chronic hepatitis C–the arc of a medical triumph. N Engl J Med 2014;370(17):1576-1578.
  31. Van der Meer AJ, et al. Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis. JAMA 2012;308(24):2584-2593.
  32. Munakata T, Nakamura M, et al. Down-regulation of the retinoblastoma tumor suppressor by the hepatitis C virus NS5B RNA-dependent RNA polymerase. Proc Natl Acad Sci U S A 2005; 102(50):18159-18164.
  33. McGivern DR, Lemon SM. Virus-specific mechanisms of carcinogenesis in hepatitis C virus associated liver cancer. Oncogene 2011;30(17):1969- 1983.
  34. Li Y, Zhang Q, et al. Hepatitis C virus activates Bcl-2 and MMP-2 expression through multiple cellular signaling pathways. J Virol 2012 Dec;86(23):12531–12543.
  35. Al Kanaani Z, Mahmud S, et al. The epidemiology of hepatitis C virus in Pakistan: systematic review and meta-analyses. R Soc Open Sci 2018;5(4).
  36. Alavian SM, Haghbin H. Relative Importance of Hepatitis B and C Viruses in Hepatocellular Carcinoma in EMRO Countries and the Middle East: A Systematic Review. Hepat Mon 2016;16(3):e35106.
  37. Khan A, Tanaka Y, et al. Epidemic spread of hepatitis C virus genotype 3a and relation to high incidence of hepatocellular carcinoma in Pakistan. J Med Virol 2009;81(7):1189-1197.
  38. El-Serag HB, Kanwal F, et al. A new laboratory-based algorithm to predict development of hepatocellular carcinoma in patients with hepatitis C and cirrhosis. Gastroenterology 2014;146(5):1249-1255.
  39. Chawla A, Chawla R, et al. Microvasular and macrovascular complications in diabetes mellitus: Distinct or continuum? Indian J Endocrinol Metab 2016;20(4):546-551.
  40. International Diabetes Federation. IDF diabetes atlas, 6th ed [Internet]. Brussels: International Diabetes Federation; c2014. Available from: http://www.idf.org/sites/default/files/EN_6E_Atlas_Full_0.pdf.
  41. Davila JA, Morgan RO, et al. Diabetes increases the risk of hepatocellular carcinoma in the United States: a population based case control study. Gut 2005;54(4):533-539.
  42. Ohishi W, Fujiwara S, et al. Risk factors for hepatocellular carcinoma in a Japanese population: a nested case-control study. Cancer Epidemiol Biomarkers Prev 2008;17(4):846-854.
  43. El-Serag HB. Hepatocellular carcinoma: recent trends in the United States. Gastroenterology 2004 Nov;127(5 Suppl 1):S27–S34.
  44. Holstein A, Hinze S, et al. Clinical implication of hepatogenous diabetes in liver cirrhosis. J Gastroenterol Hepatol 2002;17(6):677-681.
  45. Garcia-Compean D, Jaquez-Quintana JO, et al. Liver cirrhosis and diabetes: Risk factors, pathophysiology, clinical implications and management. World J Gastroenterol 2009;15(3):280-288.
  46. Vanni E, Abate ML, et al. Sites and mechanisms of insulin resistance in non obese, non-diabetic patients with chronic hepatitis C. Hepatology 2009;50(3):697-706.
  47. Kiran Z, Zuberi BF, et al. Insulin resistance in non-diabetic patients of chronic Hepatitis C. Pak J Med Sci 2013;29(1):201-204.
  48. Memon MS, Arain ZI, et al. Prevalence of type 2 diabetes mellitus in hepatitis C virus infected population: a Southeast Asian study. J Diabetes Res 2013;2013:539361.
  49. Kuske L, Mensen A, et al; Swiss Hepatitis C Cohort Study. Characteristics of patients with chronic hepatitis C who develop hepatocellular carcinoma. Swiss Med Wkly 2012;142:w13651.
  50. Fujino Y, Mizoue T, et al. Prospective study of diabetes mellitus and liver cancer in Japan. Diabetes Metab Res Rev 2001;17(5):374-379.
  51. Butt AS, Hamid S, et al. Hepatocellular carcinoma in Native South Asian Pakistani population; Trends, clinico-pathological characteristics & differences in viral marker negative & viral-hepatocellular carcinoma. BMC Research Notes 2013;6:137.
  52. Chalasani N, Younossi Z, et al. The diagnosis and management of nonalcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology 2012;55(6):2005-2023.
  53. Fan JG, Kim SU, et al. New trends on obesity and NAFLD in Asia. J Hepatol 2017;67(4):862-873.
  54. Mikolasevic I, Filipec-Kanizaj T, et al. Nonalcoholic fatty liver disease and liver transplantation – where do we stand? World J Gastroenterol 2018;24(14):1491-1506.
  55. Jain D, Nayak NC, et al. Hepatocellular carcinoma in nonalcoholic fatty liver cirrhosis and alcoholic cirrhosis: risk factor analysis in liver transplant recipients. Eur J Gastroenterol Hepatol 2012;24(7):840-848.
  56. Goh KL, Razlan H, et al. Liver cancer in Malaysia: epidemiology and clinical presentation in a multiracial Asian population. J Dig Dis 2015;16(3):152-158.
  57. Yasui K, Hashimoto E, et al. Characteristics of patients with nonalcoholic steatohepatitis who develop hepatocellular carcinoma. Clin Gastroenterol Hepatol 2011;9(5):428-433.
  58. WHO Expert Consultation. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet 2004;363(9403):157-163.
  59. The International Association for the Study of Obesity and the International Obesity Task Force. The Asia-Pacific perspective: redefining obesity and its treatment. Australia: IASO and IOTF, 2000.
  60. Calle EE, Kaaks R. Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer 2004;4(8): 579-591.
  61. Saunders D, Seidel D, et al. Systematic review: the association between obesity and hepatocellular carcinoma - epidemiological evidence. Aliment Pharmacol Ther 2010;31(10):1051-1063.
  62. Muto Y, Sato S, et al. Overweight and obesity increase the risk for liver cancer in patients with liver cirrhosis and long-term oral supplementation with branched-chain amino acid granules inhibits liver carcinogenesis in heavier patients with liver cirrhosis. Hepatol Res 2006;35(3):204-214.
  63. Polesel J, Zucchetto A, et al. The impact of obesity and diabetes mellitus on the risk of hepatocellular carcinoma. Ann Oncol 2009;20(2):353-357.
  64. Chen CL, Yang HI, 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.
  65. Williams JH, Phillips TD, et al. Human aflatoxicosis in developing countries: a review of toxicology, exposure, potential health consequences, and interventions. Am J Clin Nutr 2004;80(5):1106-1122.
  66. IARC. Chemical agents and related occupations. IARC Monogr Eval Carcinog Risks Hum 2012;100F:1-628.
  67. Groopman JD, Kensler TW, et al. Protective interventions to prevent aflatoxin-induced carcinogenesis in developing countries. Annu Rev Public Health 2008;29:187-203.
  68. Liu Y, Wu F. Global Burden of Aflatoxin-Induced Hepatocellular Carcinoma: A Risk Assessment. Environ Health Perspect 2010;118(6):818- 824.
  69. Kirk GD, Lesi OA, et al. 249(ser) P53 mutation in plasma DNA, hepatitis B viral infection, and risk of hepatocellular carcinoma. Oncogene 2005;24(38):5858-5867.
  70. Qian GS, Ross RK, et al. 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(1): 3-10.
  71. Koh WP, Robien K, et al. Smoking as an independent risk factor for hepatocellular carcinoma: the Singapore Chinese Health Study. Br J Cancer 2011;105(9):1430-1435.
  72. Chen ZM, Liu BQ, et al. Smoking and liver cancer in China: case-control comparison of 36,000 liver cancer deaths vs. 17,000 cirrhosis deaths. Int J Cancer 2003;107(1):106-112.
  73. IARC. Tobacco smoke and involuntary smoking. IARC Monogr Eval Carcinogen risks Humans 2004;83:1–1438.
  74. Sheron N, Hawkey C, et al. Projections of alcohol deaths--a wake-up call. Lancet 2011;377(9774):1297-1299.
  75. Testino G. The burden of cancer attributable to alcohol consumption. Maedica (Buchar) 2011;6(4):313-320.
  76. Secretan B, Straif K, et al. A review of human carcinogens--Part E: tobacco, areca nut, alcohol, coal smoke, and salted fish. Lancet Oncol 2009;10(11):1033-1034.
  77. Donato F, Tagger A, et al. Alcohol and hepatocellular carcinoma: the effect of lifetime intake and hepatitis virus infections in men and women. Am J Epidemiol 2002;155(4):323-331.
  78. Jee SH, Ohrr H, et al. Cigarette smoking, alcohol drinking, hepatitis B, and risk for hepatocellular carcinoma in Korea. J Natl Cancer Inst 2004;96(24):1851-1856.
  79. Alcorn T. Mongolia's struggle with liver cancer. Lancet 2011; 377(9772):1139-1140.
  80. Cai RL, Meng W, et al. Segregation analysis of hepatocellular carcinoma in a moderately high-incidence area of East China. World J Gastroenterol 2003;9(11):2428-2432.
  81. Pujol FH, Navas MC, et al. Worldwide genetic diversity of HBV genotypes and risk of hepatocellular carcinoma. Cancer Lett 2009;286(1):80-88.
  82. Turati F, Edefonti V, et al. Family history of liver cancer and hepatocellular carcinoma. Hepatology 2012;55(5):1416-1425.
  83. Chandra S, Kusum A, et al. Familial Hepatocellular Carcinoma- First Reported Case from India. J Clin Diagn Res 2016;10(3):ED11-12.
  84. Elmberg M, Hultcrantz R, et al. Cancer risk in patients with hereditary hemochromatosis and in their first-degree relatives. Gastroenterology 2003;125(6):1733-1741.
  85. Kudo M. Systemic therapy for hepatocellular carcinoma: Latest advances. Cancers (Basel) 2018;10(11).
  86. Facciorusso A, Di Maso M, et al. Microwave ablation versus radiofrequency ablation for the treatment of hepatocellular carcinoma: A systematic review and meta-analysis. Int J Hyperthermia 2016;32(3):339-344.
  87. Jun BG, Kim SG, et al. Combined therapy of transarterial chemoembolization and stereotactic body radiation therapy versus transarterial chemoembolization for <5 cm hepatocellular carcinoma: Propensity score matching analysis. PLoS One 2018;13(10).
  88. Lok AS. Prevention of hepatitis B virus-related hepatocellular carcinoma. Gastroenterology 2004;127(5 Suppl 1):S303-S309.
  89. Gentile I, Borgia G. Vertical transmission of hepatitis B virus: challenges and solutions. Int J Womens Health 2014;6:605-611.
  90. Szmuness W, Stevens CE, et al. Hepatitis B vaccine: demonstration of efficacy in a controlled clinical trial in a high-risk population in the United States. N Engl J Med 1980;303(15):833-841.
  91. Komatsu H. Hepatitis B virus: Where do we stand and what is the next step for eradication? World J Gastroenterol 2014;20(27):8998-9016.
  92. Luo Z, Li L, Ruan B. Impact of the implementation of a vaccination strategy on hepatitis B virus infections in China over a 20-year period. Int J Infect Dis 2012;16(2):e82-e88.
  93. Chang MH, You SL, et al. Decreased incidence of hepatocellular carcinoma in hepatitis B vaccinees: a 20-year follow-up study. J Natl Cancer Inst 2009;101(19):1348-1355.
  94. Liaw YF, Sung JJ, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med 2004;351(15): 1521-1531.
  95. Rosen HR. Clinical practice. Chronic hepatitis C infection. N Engl J Med 2011;364(25):2429-2438.
  96. Morgan TR, Ghany MG, et al. Outcome of sustained virological responders with histologically advanced chronic hepatitis C. Hepatology 2010 Sep;52(3):833-844.
  97. Charlton M, Everson GT, et al. Ledipasvir and sofosbuvir plus ribavirin for treatment of HCV infection in patients with advanced liver disease. Gastroenterology 2015;149(3):649-659.
  98. Conti F, Buonfiglioli F, et al. Early occurrenceand recurrence of hepatocellular carcinoma in HCVrelated cirrhosis treated with directacting antivirals. J Hepatol 2016;65(4):727-733.
  99. Reig M, Marino Z, et al. Unexpected high rate of early tumor recurrence in patients with HCV-related HCC undergoing interferonfree therapy. J Hepatol 2016;65(4):719-726.
  100. Finkelmeier F, Dultz G, et al. Risk of de novo Hepatocellular Carcinoma after HCV Treatment with Direct-Acting Antivirals. Liver Cancer 2018;7(2):190-204.
  101. Mun EJ, Green P, et al. No dif ference between directacting antivirals for hepatitis C in hepatocellular carcinoma risk. Eur J Gastroenterol Hepatol 2019;31(1):47-52.
  102. Lagiou P, Rossi M, et al. Glycemic load in relation to hepatocellular carcinoma among patients with chronic hepatitis infection. Ann Oncol 2009;20(10):1741-1745.
  103. Mandair DS, Rossi RE, et al. The impact of diet and nutrition in the prevention and progression of hepatocellular carcinoma. Expert Rev Gastroenterol Hepatol 2014;8(4):369-382.
  104. Wen CP, Wai JP, et al. Minimum amount of physical activity for reduced mortality and extended life expectancy: a prospective cohort study. Lancet 2011;378(9798):1244-1253.
  105. Wen CP, Lin J, et al. Hepatocellularcarcinoma risk prediction model for the general population: the predictivepower of transaminases. J Natl Cancer Inst 2012;104(20):1599-1611.
  106. Sang LX, Chang B, et al. Consumption of coffee associated with reduced risk of liver cancer: a meta-analysis. BMC Gastroenterol 2013;13: 34.
  107. Torres DM, Harrison SA. Is it time to write a prescription for coffee? Coffee and liver disease. Gastroenterology 2013;144:670-672.
  108. Miyanishi K, Hoki T, et al. Prevention of hepatocellular carcinoma: Focusing on antioxidant therapy. World J Hepatol 2015;7(3): 593-599.
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