Current Gastroenterology Reports

, Volume 13, Issue 1, pp 49–55 | Cite as

Modern Approach to Hepatocellular Carcinoma

  • Morris Sherman


Hepatocellular carcinoma (HCC) used to be considered a universally fatal disease. Today, however, we have tools to identify patients at risk for HCC with more accuracy. We are able to provide surveillance using ultrasonography that is sufficiently sensitive to detect small HCC lesions. Treatment of these lesions, whether by resection or by radiofrequency ablation, is highly effective. These advances mean that HCC is theoretically curable in the majority of patients, provided these tools are used. Microarray technology has been applied to the study of the genetic changes in HCC, and has defined several distinct genetic variants of this disease, as well as identifying gene signatures that predict poor outcome, and predict metastases. These techniques are now being used to identify new potential targets for therapy, and hold great promise for the future.


Hepatocellular carcinoma Surveillance Hepatitis C Hepatitis C Cirrhosis 



No potential conflict of interest relevant to this article was reported.


Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Wang CS, Yao WJ, Chang TT, et al. The impact of type 2 diabetes on the development of hepatocellular carcinoma in different viral hepatitis statuses. Cancer Epidemiol Biomarkers Prev. 2009 Jul;18(7):2054–60.CrossRefPubMedGoogle Scholar
  2. 2.
    Veldt BJ, Chen W, Heathcote EJ, et al. Increased risk of hepatocellular carcinoma among patients with hepatitis C cirrhosis and diabetes mellitus. Hepatology. 2008 Jun;47(6):1856–62.CrossRefPubMedGoogle Scholar
  3. 3.
    Bugianesi E, Leone N, Vanni E, et al. Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology. 2002 Jul;123(1):134–40.CrossRefPubMedGoogle Scholar
  4. 4.
    Polesel J, Zucchetto A, Montella M, et al. The impact of obesity and diabetes mellitus on the risk of hepatocellular carcinoma. Ann Oncol. 2009 Feb;20(2):353–7.CrossRefPubMedGoogle Scholar
  5. 5.
    Tung HD, Wang JH, Tseng PL, et al. Neither diabetes mellitus nor overweight is a risk factor for hepatocellular carcinoma in a dual HBV and HCV endemic area: community cross-sectional and case-control studies. Am J Gastroenterol. 2010 Mar;105(3):624–31.CrossRefPubMedGoogle Scholar
  6. 6.
    Paradis V, Zalinski S, Chelbi E, et al. Hepatocellular carcinomas in patients with metabolic syndrome often develop without significant liver fibrosis: a pathological analysis. Hepatology. 2009 Mar;49(3):851–9CrossRefPubMedGoogle Scholar
  7. 7.
    Yatsuji S, Hashimoto E, Tobari M, et al. Clinical features and outcomes of cirrhosis due to non-alcoholic steatohepatitis compared with cirrhosis caused by chronic hepatitis C. J Gastroenterol Hepatol. 2009 Feb;24(2):248–54.CrossRefPubMedGoogle Scholar
  8. 8.
    • Lok AS, Seeff LB, Morgan TR, et al. Incidence of hepatocellular carcinoma and associated risk factors in hepatitis C-related advanced liver disease. Gastroenterology. 2009 Jan;136(1):138–48. In this paper, the risk of noncirrhotic patients with chronic hepatitis C is documented, and a risk score developed that helps predict who among patients with chronic hepatitis C are likely to develop HCC.CrossRefPubMedGoogle Scholar
  9. 9.
    • Andersson KL, Salomon JA, Goldie SJ, et al. Cost effectiveness of alternative surveillance strategies for hepatocellular carcinoma in patients with cirrhosis. Clin Gastro Hepatol 2008;6:1418–1424. There are many cost-efficacy analyses on HCC surveillance. Most have faults that make the conclusion doubtful. This analysis most closely mirrors real life, and the conclusions are likely to be correct. In particular, it shows that surveillance with CT or MRI is hugely cost-ineffective.CrossRefGoogle Scholar
  10. 10.
    Nouso K, Tanaka H, Uematsu S, et al. Cost-effectiveness of the surveillance program of hepatocellular carcinoma depends on the medical circumstances. J Gastro Hepatol 2008:23 437–444CrossRefGoogle Scholar
  11. 11.
    Sarasin FP, Giostra E, Hadengue A. Cost effectiveness of screening for detection of small hepatocellular carcinoma in Western patients with Child Pugh class A cirrhosis. Am J Med 1996 101 422–434.CrossRefPubMedGoogle Scholar
  12. 12.
    Patel D, Terrault N, Yao F, et al. Cost-Effectiveness of Hepatocellular Carcinoma Surveillance in Patients With Hepatitis C Virus-Related Cirrhosis. Clin Gastro Hepatol 2005;3:75–84.CrossRefGoogle Scholar
  13. 13.
    Lin OS, Keeffe ED, Sanders GD, et al. Cost-effectiveness of screening for hepatocellular carcinoma in patients with cirrhosis due to chronic hepatitis C. Aliment Pharmacol Ther 2004; 19: 1159–1172.CrossRefPubMedGoogle Scholar
  14. 14.
    Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology 2005 Nov;42(5):1208–1236CrossRefPubMedGoogle Scholar
  15. 15.
    Yuen MF, Tanaka Y, Fong DY, et al. Independent risk factors and predictive score for the development of hepatocellular carcinoma in chronic hepatitis B. J Hepatol. 2009;5:80–8CrossRefGoogle Scholar
  16. 16.
    • Yang HI, Sherman M, Su J, et al. Nomograms for risk of hepatocellular carcinoma in patients with chronic hepatitis B virus infection. J Clin Oncol; 2010 28:2437–44. This paper provides an HCC risk nomogram that can be applied with clinical data available to any physician that helps determine whether a patient is at risk for the development of HCC, and who should therefore be entered into a surveillance program.CrossRefPubMedGoogle Scholar
  17. 17.
    • Lok AS, Sterling RK, Everhart JE, et al. Des-gamma-carboxy prothrombin and alpha-fetoprotein as biomarkers for the early detection of hepatocellular carcinoma. Gastroenterology. 2010 Feb;138(2):493–502. This paper clearly shows that AFP and DCP are ineffective as surveillance tools for HCC.CrossRefPubMedGoogle Scholar
  18. 18.
    Marrero JA, Feng Z, Wang Y, et al. Alpha-fetoprotein, des-gamma carboxyprothrombin, and lectin-bound alpha-fetoprotein in early hepatocellular carcinoma. Gastroenterology. 2009 Jul;137(1):110–8.CrossRefPubMedGoogle Scholar
  19. 19.
    Kim DY, Han KH, Ahn SH, et al.: Semiannual surveillance for hepatocellular carcinoma improved patient survival compared to annual surveillance (Korean experience). Hepatology 46, Suppl. 1, 403A: 2007.Google Scholar
  20. 20.
    Saab S, Ly D, Nieto J, et al. Hepatocellular Carcinoma Screening in Patients Waiting for Liver Transplantation: A Decision Analytic Model. Liver Transplantation, Vol 9, No 7 (July), 2003: pp 672–681CrossRefPubMedGoogle Scholar
  21. 21.
    Forner A, Vilana R, Ayuso C, et al. Diagnosis of hepatic nodules 20 mm or smaller in cirrhosis: Prospective validation of the noninvasive diagnostic criteria for hepatocellular carcinoma. Hepatology 2008 Jan;47(1):97–104.CrossRefPubMedGoogle Scholar
  22. 22.
    Sangiovanni A, Manini MA, Iavarone M, et al. The diagnostic and economic impact of contrast imaging technique in the diagnosis of small hepatocellular carcinoma in cirrhosis. Gut. 2009 Dec 1.Google Scholar
  23. 23.
    Khalili K, Kim TY, Jang HJ, et al. Implementation of AASLD hepatocellular carcinoma practice guidelines in North America: two years of experience. In press J Hepatol.Google Scholar
  24. 24.
    Rimola J, Forner A, Reig M, et al.: Cholangiocarcinoma in cirrhosis: absence of contrast washout in delayed phases by magnetic resonance imaging avoids misdiagnosis of hepatocellular carcinoma. Hepatology. 2009 Sep;50(3):791–8CrossRefPubMedGoogle Scholar
  25. 25.
    American Association for Study of Liver Disease website. Available at July 28 2010)
  26. 26.
    • The International Consensus Group for Hepatocellular Neoplasia. Pathologic diagnosis of early hepatocellular carcinoma: a report of the international consensus group for hepatocellular neoplasia. Hepatology 2009 Feb;49(2):658–664. This is an important paper because it describes for the first time the standardization of nomenclature for early HCC and pre-neoplastic lesions. Now East and West can speak the same language.CrossRefGoogle Scholar
  27. 27.
    Di Tommaso L, Franchi G, park YN, et al. Diagnostic value of HSP70, glypican 3 and glutamine synthetase in hepatocellular nodules in cirrhosis. Hepatology 2007 45:725–734CrossRefPubMedGoogle Scholar
  28. 28.
    Livraghi T, Meloni F, Di SM, 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 2008 Jan;47(1):82–89.CrossRefPubMedGoogle Scholar
  29. 29.
    Hoshida Y, Nijman SM, Kobayashi M, et al. Integrative transcriptome analysis reveals common molecular subclasses of human hepatocellular carcinoma. Cancer Res. 2009 Sep 15;69(18):7385–92.CrossRefPubMedGoogle Scholar
  30. 30.
    Laurent-Puig P, Legoix P, Bluteau O, et al. Genetic alterations associated with hepatocellular carcinoma define distinc pathways of hepatocarcinogenesis. Hepatology 2006 43 (2 suppl1) S145–S150.Google Scholar
  31. 31.
    Boyault S, Rickman DS, de Renies A, et al. Transcriptome classification of HCC is related to gene alteration and to new therapeutic targets. Hepatology 2007 45:42–52CrossRefPubMedGoogle Scholar
  32. 32.
    Hoshida Y, Villanueva A, Kobayashi M, et al. Gene expression in fixed tissues and outcome in hepatocellular carcinoma. N Engl J Med. 2008 Nov 6;359(19):1995–2004CrossRefPubMedGoogle Scholar
  33. 33.
    Bruix J, Llovet JM. Prognostic prediction and treatment strategy in HCC. Hepatology 2002;35:519–524.CrossRefPubMedGoogle Scholar
  34. 34.
    Vauthey JN, Lauwers GY, Esnaola NF, et al.: Simplified staging for hepatocellular carcinoma. J Clin Oncol. 2002 Mar 15;20(6):1527–36.CrossRefPubMedGoogle Scholar
  35. 35.
    Ioannou GN, Perkins JD, Carithers RL, Jr. Liver transplantation for hepatocellular carcinoma: impact of the MELD allocation system and predictors of survival. Gastroenterology. 2008 May;134(5):1342–51.CrossRefPubMedGoogle Scholar
  36. 36.
    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 2003;38:207–215.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.University of TorontoTorontoCanada
  2. 2.Toronto General HospitalTorontoCanada

Personalised recommendations