Advertisement

Current Hepatology Reports

, Volume 14, Issue 4, pp 279–283 | Cite as

Does Nucleos(t)ide (NUC) Analogs Therapy in Hepatitis B Impact the Incidence of Liver Cancer?

  • Walid S. AyoubEmail author
  • Paul Martin
  • Pietro Lampertico
Hepatitis B (J Lim, Section Editor)
  • 85 Downloads
Part of the following topical collections:
  1. Topical Collection on Hepatitis B

Abstract

Hepatocellular carcinoma (HCC) is a major source of mortality. It is the second most common cause of death worldwide, the fifth most common cancer in men, and ninth in women. It is estimated that 782,000 cases are diagnosed annually, of which half occurs on China [1]. It is more prevalent in Eastern and South-Eastern Asia and less prevalent in the USA and Northern Europe [2]. It carries a high burden on society and significantly impairs quality of life. It is estimated that up to 746,000 deaths occurs annually from hepatocellular carcinoma with approximately half of the death associated with hepatitis B [2]. Fortunately, an increasing body of evidence confirms the efficacy of HBV vaccination and antiviral therapy in reducing the incidence of HCC. In this review, we address treatment of hepatitis B and its impact on development of HCC.

Keywords

Hepatitis B Liver cancer Hepatocellular carcinoma Nucleos(t)ides Tenofovir Entecavir Lamivudine 

Notes

Compliance with Ethical Standards

Conflict of Interest

Walid S. Ayoub, Paul Martin and Pietro Lampertico declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

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

  1. 1.
    Ferlay J, Soerjomataram II, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer J Int du Cancer 2014.Google Scholar
  2. 2.
    Ferlay J, Soerjomataram I, Ervik M, et al. GLOBOCAN 2012 v1.0, Cancer incidence and mortality worldwide: IARC CancerBase No. 11 [Internet] Lyon, France: international agency for research on cancer; 2013 Available from: http://globocan.iarc.fr, accessed on 09/17/2014.
  3. 3.
    Bruix J, Sherman M, American Association for the Study of Liver D. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53:1020–2.PubMedCentralCrossRefPubMedGoogle Scholar
  4. 4.
    Chang MH, You SL, Chen CJ, et al. Decreased incidence of hepatocellular carcinoma in hepatitis B vaccinees: a 20-year follow-up study. J Natl Cancer Inst. 2009;101:1348–55.CrossRefPubMedGoogle Scholar
  5. 5.
    Liaw YF, Sung JJ, Chow WC, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med. 2004;351:1521–31.CrossRefPubMedGoogle Scholar
  6. 6.
    Marcellin P, Buti M, Krastev Z, et al. Kinetics of hepatitis B surface antigen loss in patients with HBeAg-positive chronic hepatitis B treated with tenofovir disoproxil fumarate. J Hepatol. 2014;61:1228–37.CrossRefPubMedGoogle Scholar
  7. 7.
    Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology. 2009;50:661–2.CrossRefPubMedGoogle Scholar
  8. 8.
    Gish RG, Chang TT, Lai CL, et al. Loss of HBsAg antigen during treatment with entecavir or lamivudine in nucleoside-naive HBeAg-positive patients with chronic hepatitis B. J Viral Hepat. 2010;17:16–22.CrossRefPubMedGoogle Scholar
  9. 9.
    Ayoub WS, Keeffe EB. Review article: current antiviral therapy of chronic hepatitis B. Aliment Pharmacol Ther. 2011;34:1145–58.CrossRefPubMedGoogle Scholar
  10. 10.
    Vlachogiannakos J, Papatheodoridis G. Hepatocellular carcinoma in chronic hepatitis B patients under antiviral therapy. World J Gastroenterology: WJG. 2013;19:8822–30.PubMedCentralCrossRefPubMedGoogle Scholar
  11. 11.
    Kao JH, Liu CJ, Jow GM, Chen PJ, Chen DS, Chen BF. Fine mapping of hepatitis B virus pre-S deletion and its association with hepatocellular carcinoma. Liver Int: Off J Int Assoc Study Liver. 2012;32:1373–81.CrossRefGoogle Scholar
  12. 12.
    Tseng TC, Liu CJ, Yang HC, et al. High levels of hepatitis B surface antigen increase risk of hepatocellular carcinoma in patients with low HBV load. Gastroenterology. 2012;142:1140–9 e3. quiz e13-4.CrossRefPubMedGoogle Scholar
  13. 13.•
    Triolo M, Della Corte C, Colombo M. Impact of HBV therapy on the incidence of hepatocellular carcinoma. Liver Int: Off J Int Assoc Study Liver. 2014;34 Suppl 1:139–45. The bulleted references provide an updated analysis of the literature demonstrating the chemopreventive properties of NA therapy. The references demonstrate the impact of hepatitis B therapy on the risk of development of HCC with oral agents with low and high genetic barriers to resistance. CrossRefGoogle Scholar
  14. 14.
    Fattovich G, Bortolotti F, Donato F. Natural history of chronic hepatitis B: special emphasis on disease progression and prognostic factors. J Hepatol. 2008;48:335–52.CrossRefPubMedGoogle Scholar
  15. 15.
    Sung JJ, Tsoi KK, Wong VW, Li KC, Chan HL. Meta-analysis: treatment of hepatitis B infection reduces risk of hepatocellular carcinoma. Aliment Pharmacol Ther. 2008;28:1067–77.CrossRefPubMedGoogle Scholar
  16. 16.•
    Papatheodoridis GV, Lampertico P, Manolakopoulos S, Lok A. Incidence of hepatocellular carcinoma in chronic hepatitis B patients receiving nucleos(t)ide therapy: a systematic review. J Hepatol. 2010;53:348–56. The bulleted references provide an updated analysis of the literature demonstrating the chemopreventive properties of NA therapy. The references demonstrate the impact of hepatitis B therapy on the risk of development of HCC with oral agents with low and high genetic barriers to resistance. CrossRefPubMedGoogle Scholar
  17. 17.
    Jeng WJ, Sheen IS, Chen YC, et al. Off-therapy durability of response to entecavir therapy in hepatitis B e antigen-negative chronic hepatitis B patients. Hepatology. 2013;58:1888–96.CrossRefPubMedGoogle Scholar
  18. 18.••
    Liaw YF. Impact of therapy on the long-term outcome of chronic hepatitis B. Clinics Liver Dis. 2013;17:413–23. The bulleted references provide an updated analysis of the literature demonstrating the chemopreventive properties of NA therapy. The references demonstrate the impact of hepatitis B therapy on the risk of development of HCC with oral agents with low and high genetic barriers to resistance. CrossRefGoogle Scholar
  19. 19.
    Hosaka T, Suzuki F, Kobayashi M, et al. Long-term entecavir treatment reduces hepatocellular carcinoma incidence in patients with hepatitis B virus infection. Hepatology. 2013;58:98–107.CrossRefPubMedGoogle Scholar
  20. 20.
    Wong GL, Chan HL, Mak CW, et al. Entecavir treatment reduces hepatic events and deaths in chronic hepatitis B patients with liver cirrhosis. Hepatology. 2013;58:1537–47.CrossRefPubMedGoogle Scholar
  21. 21.
    Kumada T, Toyoda H, Tada T, et al. Effect of nucleos(t)ide analogue therapy on hepatocarcinogenesis in chronic hepatitis B patients: a propensity score analysis. J Hepatol. 2013;58:427–33.CrossRefPubMedGoogle Scholar
  22. 22.
    Chang TT, Liaw YF, Wu SS, et al. Long-term entecavir therapy results in the reversal of fibrosis/cirrhosis and continued histological improvement in patients with chronic hepatitis B. Hepatology. 2010;52:886–93.CrossRefPubMedGoogle Scholar
  23. 23.••
    Coffin CS, Rezaeeaval M, Pang JX, et al. The incidence of hepatocellular carcinoma is reduced in patients with chronic hepatitis B on long-term nucleos(t)ide analogue therapy. Aliment Pharmacol Ther. 2014;40:1262–9. The bulleted references provide an updated analysis of the literature demonstrating the chemopreventive properties of NA therapy. The references demonstrate the impact of hepatitis B therapy on the risk of development of HCC with oral agents with low and high genetic barriers to resistance. CrossRefPubMedGoogle Scholar
  24. 24.
    Marcellin P, Gane E, Buti M, et al. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. Lancet. 2013;381:468–75.CrossRefPubMedGoogle Scholar
  25. 25.
    Kim W, Berg T, Loomba R, et al. Long term tenofovir disoproxil fumarate (TDF) therapy and the risk of hepatocellular carcinoma. J Hepatol. 2013;58:S19.CrossRefGoogle Scholar
  26. 26.
    Papatheodoridis GV, Dalekos GN, Yurdaydin C, et al. Incidence and predictors of hepatocellular carcinoma in Caucasian chronic hepatitis B patients receiving entecavir or tenofovir. J Hepatol 2014.Google Scholar
  27. 27.••
    Papatheodoridis GV, Chan HL, Hansen BE, Janssen HL, Lampertico P. Risk of hepatocellular carcinoma in chronic hepatitis B: assessment and modification with current antiviral therapy. J Hepatol. 2015;62:956–67. The bulleted references provide an updated analysis of the literature demonstrating the chemopreventive properties of NA therapy. The references demonstrate the impact of hepatitis B therapy on the risk of development of HCC with oral agents with low and high genetic barriers to resistance. CrossRefPubMedGoogle Scholar
  28. 28.
    Huang G, Lau WY, Wang ZG, et al. Antiviral therapy improves postoperative survival in patients with hepatocellular carcinoma: a randomized controlled trial. Ann Surg. 2015;261:56–66.CrossRefPubMedGoogle Scholar
  29. 29.
    Wu CY, Chen YJ, Ho HJ, et al. Association between nucleoside analogues and risk of hepatitis B virus-related hepatocellular carcinoma recurrence following liver resection. JAMA: J Am Med Assoc. 2012;308:1906–14.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Walid S. Ayoub
    • 1
    Email author
  • Paul Martin
    • 2
  • Pietro Lampertico
    • 3
  1. 1.Department of Digestive and Liver DiseasesCedars Sinai Medical CenterLos AngelesUSA
  2. 2.University Miami School of MedicineMiamiUSA
  3. 3.Gastroenterology and Hepatology Division, Fondazione IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoUniversità di MilanoMilanItaly

Personalised recommendations