Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Hepatocellular carcinoma: a global view

Abstract

Hepatocellular carcinoma (HCC) is a global health problem, although developing countries are disproportionally affected: over 80% of HCCs occur in such regions. About three-quarters of HCCs are attributed to chronic HBV and HCV infections. In areas endemic for HCV and HBV, viral transmission occurs at an early age, and infected individuals develop HCC in mid-adulthood. As these are their most productive years of life, HCC accounts for a substantial burden on the health-care system and drain of productive capacity in the low-income and middle-income countries most affected by HCV and HBV infections. Environments with disparate resource levels require different strategies for the optimal management of HCC. In high-resource environments, guidelines from the American Association for the Study of Liver Diseases or European Association for the Study of the Liver should be applied. In intermediate-resource or low-resource environments, the fundamental focus should be on primary prevention of HCC, through universal HBV vaccination, taking appropriate precautions and antiviral treatments. In intermediate-resource and low-resource environments, the infrastructure and capacity for abdominal ultrasonography, percutaneous ethanol injection, radiofrequency ablation and surgical resection should be established. Programs to provide targeted therapy at low cost, similar to the approach used for HIV therapy in the developing world, should be pursued.

Key Points

  • Hepatocellular carcinoma (HCC) is the seventh most common cancer and the third leading cause of cancer-related deaths in the world

  • Over 80% of HCCs occur in developing countries, which lack infrastructure for the management of this disease

  • High-resource environments should utilize American Association for the Study of Liver Diseases or European Association for the Study of the Liver guidelines for HCC prevention, surveillance, diagnosis and treatment

  • In intermediate-resource or low-resource environments, primary prevention of HCC through universal HBV vaccination, appropriate precautions and antiviral treatment should be the primary focus

  • The infrastructure and capacity for high-quality ultrasonography, percutaneous ethanol injection, radiofrequency ablation and surgical resection are crucial

  • Programs to provide targeted therapy at low cost, similar to those used for HIV therapy, should be pursued in resource-poor environments

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: Global variations in age-adjusted incidence rates of liver cancer, prevalence of chronic HCV infection and chronic HBV infection.
Figure 2: Age-specific incidence rates of hepatocellular carcinoma among men in China and Gambia (West Africa).
Figure 3: Estimated attributable fractions of primary hepatocellular cancers with a viral etiology in countries with different levels of medical resources (data from Bosch et al. [2004]).13
Figure 4: Change in the incidence rates of hepatocellular carcinoma between 1983 and 2004.

References

  1. Ferlay, J. et al. GLOBOCAN 2008, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 10 Lyon, France: International Agency for Research on Cancer [online], (2010).

  2. The World Health Organization GLOBOCAN 2002 [online], (2002).

  3. McGlynn, K. A., Tsao, L., Hsing, A. W., Devesa, S. S. & Fraumeni, J. F. Jr. International trends and patterns of primary liver cancer. Int. J. Cancer 94, 290–296 (2001).

    CAS  PubMed  Google Scholar 

  4. Altekruse, S. F., McGlynn, K. A. & Reichman, M. E. Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005. J. Clin. Oncol. 27, 1485–1491 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Armstrong, G. L., Alter, M. J., McQuillan, G. M. & Margolis, H. S. The past incidence of hepatitis C virus infection: implications for the future burden of chronic liver disease in the United States. Hepatology 31, 777–782 (2000).

    CAS  PubMed  Google Scholar 

  6. Davila, J. A., Morgan, R. O., Shaib, Y., McGlynn, K. A. & El-Serag, H. B. Hepatitis C infection and the increasing incidence of hepatocellular carcinoma: a population-based study. Gastroenterology 127, 1372–1380 (2004).

    PubMed  Google Scholar 

  7. Marrero, J. A. et al. NAFLD may be a common underlying liver disease in patients with hepatocellular carcinoma in the United States. Hepatology 36, 1349–1354 (2002).

    PubMed  Google Scholar 

  8. Evans, A. A. et al. Geographic variation in viral load among hepatitis B carriers with differing risks of hepatocellular carcinoma. Cancer Epidemiol. Biomarkers Prev. 7, 559–565 (1998).

    CAS  PubMed  Google Scholar 

  9. El-Serag, H. B. & Rudolph, K. L. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 132, 2557–2576 (2007).

    CAS  PubMed  Google Scholar 

  10. Parkin, D. M., Bray, F., Ferlay, J. & Pisani, P. Global cancer statistics, 2002. CA Cancer J. Clin. 55, 74–108 (2005).

    PubMed  Google Scholar 

  11. Naugler, W. E. et al. Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production. Science 317, 121–124 (2007).

    CAS  PubMed  Google Scholar 

  12. Yu, M. W. & Chen, C. J. Elevated serum testosterone levels and risk of hepatocellular carcinoma. Cancer Res. 53, 790–794 (1993).

    CAS  PubMed  Google Scholar 

  13. Bosch, F. X., Ribes, J., Diaz, M. & Cléries, R. Primary liver cancer: worldwide incidence and trends. Gastroenterology 127 (Suppl. 1), S5–S16 (2004).

    PubMed  Google Scholar 

  14. Parkin, D. M. The global health burden of infection-associated cancers in the year 2002. Int. J. Cancer 118, 3030–3044 (2006).

    CAS  PubMed  Google Scholar 

  15. Beasley, R. P. Hepatitis B virus. The major etiology of hepatocellular carcinoma. Cancer 61, 1942–1956 (1988).

    CAS  PubMed  Google Scholar 

  16. Chen, J. D. et al. Carriers of inactive hepatitis B virus are still at risk for hepatocellular carcinoma and liver-related death. Gastroenterology 138, 1747–1754 (2010).

    PubMed  Google Scholar 

  17. Yuen, M. F. et al. Independent risk factors and predictive score for the development of hepatocellular carcinoma in chronic hepatitis B. J. Hepatol. 50, 80–88 (2009).

    PubMed  Google Scholar 

  18. Yang, H. I. et al. Nomograms for risk of hepatocellular carcinoma in patients with chronic hepatitis B virus infection. J. Clin. Oncol. 28, 2437–2444 (2010).

    PubMed  Google Scholar 

  19. Liu, S. et al. Associations between hepatitis B virus mutations and the risk of hepatocellular carcinoma: a meta-analysis. J. Natl Cancer Inst. 101, 1066–1082 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Yang, H. I. et al. Associations between hepatitis B virus genotype and mutants and the risk of hepatocellular carcinoma. J. Natl Cancer Inst. 100, 1134–1143 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Kao, J. H. Role of viral factors in the natural course and therapy of chronic hepatitis B. Hepatol. Int. 1, 415–430 (2007).

    PubMed  PubMed Central  Google Scholar 

  22. Chen, C. J. et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA 295, 65–73 (2006).

    CAS  PubMed  Google Scholar 

  23. Yang, H. I. et al. Hepatitis B e antigen and the risk of hepatocellular carcinoma. N. Engl. J. Med. 347, 168–174 (2002).

    CAS  PubMed  Google Scholar 

  24. Frodsham, A. J. et al. Class II cytokine receptor gene cluster is a major locus for hepatitis B persistence. Proc. Natl Acad. Sci. USA 103, 9148–9153 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Chu, C. J., Hussain, M. & Lok, A. S. Hepatitis B virus genotype B is associated with earlier HBeAg seroconversion compared with hepatitis B virus genotype C. Gastroenterology 122, 1756–1762 (2002).

    CAS  PubMed  Google Scholar 

  26. Chu, C. J. et al. Hepatitis B virus genotypes in the United States: results of a nationwide study. Gastroenterology 125, 444–451 (2003).

    PubMed  Google Scholar 

  27. Livingston, S. E. et al. Clearance of hepatitis B e antigen in patients with chronic hepatitis B and genotypes A, B, C, D, and F. Gastroenterology 133, 1452–1457 (2007).

    CAS  PubMed  Google Scholar 

  28. Di Bisceglie, A. M. et al. Hepatitis C-related hepatocellular carcinoma in the United States: influence of ethnic status. Am. J. Gastroenterol. 98, 2060–2063 (2003).

    PubMed  Google Scholar 

  29. Sun, C. A. et al. Incidence and cofactors of hepatitis C virus-related hepatocellular carcinoma: a prospective study of 12,008 men in Taiwan. Am. J. Epidemiol. 157, 674–682 (2003).

    PubMed  Google Scholar 

  30. Lam, J. P. et al. Infrequent vertical transmission of hepatitis C virus. J. Infect. Dis. 167, 572–576 (1993).

    CAS  PubMed  Google Scholar 

  31. Ohto, H. et al. Transmission of hepatitis C virus from mothers to infants. The Vertical Transmission of Hepatitis C Virus Collaborative Study Group. N. Engl. J. Med. 330, 744–750 (1994).

    CAS  PubMed  Google Scholar 

  32. Alter, M. J. et al. The prevalence of hepatitis C virus infection in the United States, 1988 through 1994. N. Engl. J. Med. 341, 556–562 (1999).

    CAS  PubMed  Google Scholar 

  33. Bronowicki, J. P. et al. Patient-to-patient transmission of hepatitis C virus during colonoscopy. N. Engl. J. Med. 337, 237–240 (1997).

    CAS  PubMed  Google Scholar 

  34. Mele, A. et al. Risk of parenterally transmitted hepatitis following exposure to surgery or other invasive procedures: results from the hepatitis surveillance system in Italy. J. Hepatol. 35, 284–289 (2001).

    CAS  PubMed  Google Scholar 

  35. Karmochkine, M., Carrat, F., Dos Santos, O., Cacoub, P. & Raguin, G. A case-control study of risk factors for hepatitis C infection in patients with unexplained routes of infection. J. Viral Hepat. 13, 775–782 (2006).

    CAS  PubMed  Google Scholar 

  36. Martínez-Bauer, E. et al. Hospital admission is a relevant source of hepatitis C virus acquisition in Spain. J. Hepatol. 48, 20–27 (2008).

    PubMed  Google Scholar 

  37. Donahue, J. G. et al. The declining risk of post-transfusion hepatitis C virus infection. N. Engl. J. Med. 327, 369–373 (1992).

    CAS  PubMed  Google Scholar 

  38. Schreiber, G. B., Busch, M. P., Kleinman, S. H. & Korelitz, J. J. The risk of transfusion-transmitted viral infections. The Retrovirus Epidemiology Donor Study. N. Engl. J. Med. 334, 1685–1690 (1996).

    CAS  PubMed  Google Scholar 

  39. Hassan, M. M. et al. Risk factors for hepatocellular carcinoma: synergism of alcohol with viral hepatitis and diabetes mellitus. Hepatology 36, 1206–1213 (2002).

    CAS  PubMed  Google Scholar 

  40. Ikeda, K. et al. Antibody to hepatitis B core antigen and risk for hepatitis C-related hepatocellular carcinoma: a prospective study. Ann. Intern. Med. 146, 649–656 (2007).

    PubMed  Google Scholar 

  41. Ohki, T. et al. Obesity is an independent risk factor for hepatocellular carcinoma development in chronic hepatitis C patients. Clin. Gastroenterol. Hepatol. 6, 459–464 (2008).

    PubMed  Google Scholar 

  42. Lok, A. S. et al. Incidence of hepatocellular carcinoma and associated risk factors in hepatitis C-related advanced liver disease. Gastroenterology 136, 138–148 (2009).

    CAS  PubMed  Google Scholar 

  43. Chen, C. L. et al. Metabolic factors and risk of hepatocellular carcinoma by chronic hepatitis B/C infection: a follow-up study in Taiwan. Gastroenterology 135, 111–121 (2008).

    CAS  PubMed  Google Scholar 

  44. El-Serag, H. B. & Mason, A. C. Risk factors for the rising rates of primary liver cancer in the United States. Arch. Intern. Med. 160, 3227–3230 (2000).

    CAS  PubMed  Google Scholar 

  45. Frezza, M. et al. High blood alcohol levels in women. The role of decreased gastric alcohol dehydrogenase activity and first-pass metabolism. N. Engl. J. Med. 322, 95–99 (1990).

    CAS  PubMed  Google Scholar 

  46. Donato, F. et al. Alcohol and hepatocellular carcinoma: the effect of lifetime intake and hepatitis virus infections in men and women. Am. J. Epidemiol. 155, 323–331 (2002).

    CAS  PubMed  Google Scholar 

  47. Adams, L. A. et al. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology 129, 113–121 (2005).

    PubMed  Google Scholar 

  48. Flegal, K. M., Carroll, M. D., Ogden, C. L. & Curtin, L. R. Prevalence and trends in obesity among US adults, 1999–2008. JAMA 303, 235–241 (2010).

    CAS  PubMed  Google Scholar 

  49. Ogden, C. L. et al. Prevalence of overweight and obesity in the United States, 1999–2004. JAMA 295, 1549–1555 (2006).

    CAS  PubMed  Google Scholar 

  50. Qian, G. S. 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. 3, 3–10 (1994).

    CAS  PubMed  Google Scholar 

  51. Yu, S. Z. Primary prevention of hepatocellular carcinoma. J. Gastroenterol. Hepatol. 10, 674–682 (1995).

    CAS  PubMed  Google Scholar 

  52. Turner, P. C. et al. The role of aflatoxins and hepatitis viruses in the etiopathogenesis of hepatocellular carcinoma: A basis for primary prevention in Guinea-Conakry, West Africa. J. Gastroenterol. Hepatol. 17 (Suppl.), S441–S448 (2002).

    PubMed  Google Scholar 

  53. Ni, Y. H. et al. Hepatitis B virus infection in children and adolescents in a hyperendemic area: 15 years after mass hepatitis B vaccination. Ann. Intern. Med. 135, 796–800 (2001).

    CAS  PubMed  Google Scholar 

  54. Chang, M. H. et al. Decreased incidence of hepatocellular carcinoma in hepatitis B vaccinees: a 20-year follow-up study. J. Natl Cancer Inst. 101, 1348–1355 (2009).

    CAS  PubMed  Google Scholar 

  55. Liaw, Y. F. et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N. Engl. J. Med. 351, 1521–1531 (2004).

    CAS  PubMed  Google Scholar 

  56. Matsumoto, A. et al. Efficacy of lamivudine for preventing hepatocellular carcinoma in chronic hepatitis B: A multicenter retrospective study of 2795 patients. Hepatol. Res. 32, 173–184 (2005).

    CAS  PubMed  Google Scholar 

  57. Yuen, M. F. et al. Long-term lamivudine therapy reduces the risk of long-term complications of chronic hepatitis B infection even in patients without advanced disease. Antivir. Ther. 12, 1295–1303 (2007).

    CAS  PubMed  Google Scholar 

  58. Cammà, C., Giunta, M., Andreone, P. & Craxì, A. Interferon and prevention of hepatocellular carcinoma in viral cirrhosis: an evidence-based approach. J. Hepatol. 34, 593–602 (2001).

    PubMed  Google Scholar 

  59. Nishiguchi, S. et al. Prevention of hepatocellular carcinoma in patients with chronic active hepatitis C and cirrhosis. Lancet 357, 196–197 (2001).

    CAS  PubMed  Google Scholar 

  60. Yoshida, H. 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. 131, 174–181 (1999).

    CAS  PubMed  Google Scholar 

  61. Papatheodoridis, G. V., Papadimitropoulos, V. C. & Hadziyannis, S. J. Effect of interferon therapy on the development of hepatocellular carcinoma in patients with hepatitis C virus-related cirrhosis: a meta-analysis. Aliment. Pharmacol. Ther. 15, 689–698 (2001).

    CAS  PubMed  Google Scholar 

  62. Zhang, B. H., Yang, B. H. & Tang, Z. Y. Randomized controlled trial of screening for hepatocellular carcinoma. J. Cancer Res. Clin. Oncol. 130, 417–422 (2004).

    PubMed  Google Scholar 

  63. Trevisani, F. et al. Semiannual and annual surveillance of cirrhotic patients for hepatocellular carcinoma: effects on cancer stage and patient survival (Italian experience). Am. J. Gastroenterol. 97, 734–744 (2002).

    PubMed  Google Scholar 

  64. Marrero, J. A. et al. Alpha-fetoprotein, des-gamma carboxyprothrombin, and lectin-bound alpha-fetoprotein in early hepatocellular carcinoma. Gastroenterology 137, 110–118 (2009).

    CAS  PubMed  Google Scholar 

  65. Bruix, J. & Sherman, M. Management of hepatocellular carcinoma. Hepatology 42, 1208–1236 (2005).

    PubMed  Google Scholar 

  66. Silva, M. A. et al. Needle track seeding following biopsy of liver lesions in the diagnosis of hepatocellular cancer: a systematic review and meta-analysis. Gut 57, 1592–1596 (2008).

    CAS  PubMed  Google Scholar 

  67. Llovet, J. M., Brú, C. & Bruix, J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin. Liver Dis. 19, 329–338 (1999).

    CAS  PubMed  Google Scholar 

  68. [No authors listed] A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patients: the Cancer of the Liver Italian Program (CLIP) investigators. Hepatology 28, 751–755 (1998).

  69. Lei, H. J. et al. Prognostic value and clinical relevance of the 6th Edition 2002 American Joint Committee on Cancer staging system in patients with resectable hepatocellular carcinoma. J. Am. Coll. Surg. 203, 426–435 (2006).

    PubMed  Google Scholar 

  70. Okuda, K. et al. Natural history of hepatocellular carcinoma and prognosis in relation to treatment. Study of 850 patients. Cancer 56, 918–928 (1985).

    CAS  PubMed  Google Scholar 

  71. Kudo, M., Chung, H. & Osaki, Y. Prognostic staging system for hepatocellular carcinoma (CLIP score): its value and limitations, and a proposal for a new staging system, the Japan Integrated Staging Score (JIS score). J. Gastroenterol. 38, 207–215 (2003).

    PubMed  Google Scholar 

  72. Forner, A., Reig, M. E., de Lope, C. R. & Bruix, J. Current strategy for staging and treatment: the BCLC update and future prospects. Semin. Liver Dis. 30, 61–74 (2010).

    CAS  PubMed  Google Scholar 

  73. Farinati, F. et al. Early and very early hepatocellular carcinoma: when and how much do staging and choice of treatment really matter? A multi-center study. BMC Cancer 9, 33 (2009).

    PubMed  PubMed Central  Google Scholar 

  74. Imamura, H. et al. Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy. J. Hepatol. 38, 200–207 (2003).

    PubMed  Google Scholar 

  75. Llovet, J. M., Fuster, J. & Bruix, J. Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation. Hepatology 30, 1434–1440 (1999).

    CAS  PubMed  Google Scholar 

  76. Teh, S. H. et al. Hepatic resection of hepatocellular carcinoma in patients with cirrhosis: Model of End-Stage Liver Disease (MELD) score predicts perioperative mortality. J. Gastrointest. Surg. 9, 1207–1215 (2005).

    PubMed  Google Scholar 

  77. Mazzaferro, V. et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N. Engl. J. Med. 334, 693–699 (1996).

    CAS  PubMed  Google Scholar 

  78. Yao, F. Y. et al. Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology 33, 1394–1403 (2001).

    CAS  PubMed  Google Scholar 

  79. D'Amico, F. et al. Predicting recurrence after liver transplantation in patients with hepatocellular carcinoma exceeding the up-to-seven criteria. Liver Transpl. 15, 1278–1287 (2009).

    PubMed  Google Scholar 

  80. Yao, F. Y. et al. A prospective study on downstaging of hepatocellular carcinoma prior to liver transplantation. Liver Transpl. 11, 1505–1514 (2005).

    PubMed  Google Scholar 

  81. Yao, F. Y. et al. Excellent outcome following down-staging of hepatocellular carcinoma prior to liver transplantation: an intention-to-treat analysis. Hepatology 48, 819–827 (2008).

    PubMed  Google Scholar 

  82. Trotter, J. F., Wachs, M., Everson, G. T. & Kam, I. Adult-to-adult transplantation of the right hepatic lobe from a living donor. N. Engl. J. Med. 346, 1074–1082 (2002).

    PubMed  Google Scholar 

  83. Vakili, K. et al. Living donor liver transplantation for hepatocellular carcinoma: Increased recurrence but improved survival. Liver Transpl. 15, 1861–1866 (2009).

    PubMed  Google Scholar 

  84. Vilana, R. et al. Tumor size determines the efficacy of percutaneous ethanol injection for the treatment of small hepatocellular carcinoma. Hepatology 16, 353–357 (1992).

    CAS  PubMed  Google Scholar 

  85. Lin, S. M., Lin, C. J., Lin, C. C., Hsu, C. W. & Chen, Y. C. Radiofrequency ablation improves prognosis compared with ethanol injection for hepatocellular carcinoma < or =4 cm. Gastroenterology 127, 1714–1723 (2004).

    PubMed  Google Scholar 

  86. Chen, M. S. et al. A prospective randomized trial comparing percutaneous local ablative therapy and partial hepatectomy for small hepatocellular carcinoma. Ann. Surg. 243, 321–328 (2006).

    PubMed  PubMed Central  Google Scholar 

  87. Lau, W. Y. & Lai, E. C. The current role of radiofrequency ablation in the management of hepatocellular carcinoma: a systematic review. Ann. Surg. 249, 20–25 (2009).

    PubMed  Google Scholar 

  88. Livraghi, T. et al. Sustained complete response and complications rates after radiofrequency ablation of very early hepatocellular carcinoma in cirrhosis: Is resection still the treatment of choice? Hepatology 47, 82–89 (2008).

    PubMed  Google Scholar 

  89. Lü, M. D. et al. Surgical resection versus percutaneous thermal ablation for early-stage hepatocellular carcinoma: a randomized clinical trial [Chinese]. Zhonghua Yi Xue Za Zhi 86, 801–805 (2006).

    PubMed  Google Scholar 

  90. Llovet, J. M. et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet 359, 1734–1739 (2002).

    PubMed  Google Scholar 

  91. Lo, C. M. et al. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology 35, 1164–1171 (2002).

    CAS  PubMed  Google Scholar 

  92. Alba, E. et al. Transcatheter arterial chemoembolization in patients with hepatocellular carcinoma on the waiting list for orthotopic liver transplantation. AJR Am. J. Roentgenol. 190, 1341–1348 (2008).

    PubMed  Google Scholar 

  93. Chan, A. O., Yuen, M. F., Hui, C. K., Tso, W. K. & Lai, C. L. A prospective study regarding the complications of transcatheter intraarterial lipiodol chemoembolization in patients with hepatocellular carcinoma. Cancer 94, 1747–1752 (2002).

    PubMed  Google Scholar 

  94. Dhanasekaran, R. et al. Comparison of conventional transarterial chemoembolization (TACE) and chemoembolization with doxorubicin drug eluting beads (DEB) for unresectable hepatocelluar carcinoma (HCC). J. Surg. Oncol. 101, 476–480 (2010).

    PubMed  Google Scholar 

  95. Lammer, J. et al. Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study. Cardiovasc. Intervent. Radiol. 33, 41–52 (2010).

    PubMed  Google Scholar 

  96. Geschwind, J. F. et al. Yttrium-90 microspheres for the treatment of hepatocellular carcinoma. Gastroenterology 127 (Suppl. 1), S194–S205 (2004).

    CAS  PubMed  Google Scholar 

  97. Sangro, B. et al. Radioembolization using 90Y-resin microspheres for patients with advanced hepatocellular carcinoma. Int. J. Radiat. Oncol. Biol. Phys. 66, 792–800 (2006).

    CAS  PubMed  Google Scholar 

  98. Roberts, L. R. & Gores, G. J. Hepatocellular carcinoma: molecular pathways and new therapeutic targets. Semin. Liver Dis. 25, 212–225 (2005).

    CAS  PubMed  Google Scholar 

  99. Llovet, J. M. et al. Sorafenib in advanced hepatocellular carcinoma. N. Engl. J. Med. 359, 378–390 (2008).

    CAS  PubMed  Google Scholar 

  100. Cheng, A. L. et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 10, 25–34 (2009).

    CAS  PubMed  Google Scholar 

  101. ClinicalTrials.gov Sorafenib as adjuvant treatment in the prevention of recurrence of hepatocellular carcinoma (STORM) [online], (2010).

  102. ClinicalTrials.gov A phase II randomized, double-blind, placebo-controlled study of sorafenib or placebo in combination with transarterial chemoembolization (TACE) performed with DC bead and doxorubicin for intermediate stage hepatocellular carcinoma (HCC) [online], (2010).

  103. The World Gastrointestinal Organization WGO practice guideline—hepatocellular carcinoma (HCC): a global perspective [online], (2009).

  104. Bruix, J. et al. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J. Hepatol. 35, 421–430 (2001).

    CAS  PubMed  Google Scholar 

  105. Bendavid, E. & Bhattacharya, J. The President's Emergency Plan for AIDS Relief in Africa: an evaluation of outcomes. Ann. Intern. Med. 150, 688–695 (2009).

    PubMed  PubMed Central  Google Scholar 

  106. US Centers for Disease Control and Prevention Recommendations for identification and public health management of persons with chronic hepatitis B virus infection [online], (2008).

  107. WHO International Travel and Health Global prevalence of hepatitis A, B and C [online], (2002).

Download references

Acknowledgements

This work was supported by NIH grants CA100882 and CA128633 (awarded to L. R. Roberts). We apologize to the many excellent contributors to this field whose work is not acknowledged in the reference list owing to space limitations.

Désirée Lie, University of California, Irvine, CA is the author of and is solely responsible for the content of the learning objectives, questions and answers of the MedscapeCME-accredited continuing medical education activity associated with this article.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Lewis R. Roberts.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Yang, J., Roberts, L. Hepatocellular carcinoma: a global view. Nat Rev Gastroenterol Hepatol 7, 448–458 (2010). https://doi.org/10.1038/nrgastro.2010.100

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrgastro.2010.100

This article is cited by

Search

Quick links

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer