The influence of hepatitis B DNA level and antiviral therapy on recurrence after initial curative treatment in patients with hepatocellular carcinoma

  • 503 Accesses

  • 83 Citations



Prediction and prevention of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) recurrence is an important clinical issue. We investigated whether HBV DNA level and antiviral therapy are associated with HCC recurrence.


This retrospective study involved 103 patients who underwent hepatic resection or radiofrequency ablation for initial HCC. Patients were divided into four groups. Thirty had high serum HBV DNA levels (>4 log10 copies/mL) and had not received antiviral therapy (high virus group; HVG). Thirty-four had low HBV DNA levels (≤4 log10 copies/mL) and had not received antiviral therapy (low virus group; LVG). Twenty received antiviral therapy after HCC developed (therapeutic group A, TG-A). Nineteen received antiviral therapy before HCC developed (therapeutic group B, TG-B).


Cumulative HCC recurrence rates at 3 years in the HVG, LVG, TG-B, and TG-A were 71.1%, 42.2%, 42.3%, and 52.0%, respectively. Recurrence rates differed significantly between the HVG and LVG (P = 0.016) and between the HVG and TG-B (P = 0.008). Recurrence rate in the TG-A was marginally lower than in the HVG (P = 0.10). On multivariate analysis, high serum hepatitis B virus DNA levels (hazard ratio: HR 2.67; 95% CI 1.31–5.47; P = 0.007) and absence of antiviral therapy (HR 2.57; 95% CI 1.34–4.94; P = 0.005) were independent risk factors for hepatocellular carcinoma recurrence.


HBV DNA level and antiviral therapy are associated with HCC recurrence. For patients with high HBV DNA levels, antiviral therapy before the development of HCC is important for prevention of recurrence.

This is a preview of subscription content, log in to check access.

Access options

Buy single article

Instant unlimited access to the full article PDF.

US$ 39.95

Price includes VAT for USA

Subscribe to journal

Immediate online access to all issues from 2019. Subscription will auto renew annually.

US$ 99

This is the net price. Taxes to be calculated in checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4


  1. 1.

    Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.

  2. 2.

    Befeler AS, Di Bisceglie AM. Hepatocellular carcinoma: diagnosis and treatment. Gastroenterology. 2002;122:1609–19.

  3. 3.

    Song TJ, Ip EW, Fong Y. Hepatocellular carcinoma: current surgical management. Gastroenterology. 2004;127:S248–60.

  4. 4.

    Ioannou GN, Perkins JD, Carithers RL Jr. Liver transplantation for hepatocellular carcinoma: impact of the MELD allocation system and predictors of survival. Gastroenterology. 2008;134:1342–51.

  5. 5.

    Shiina S, Teratani T, Obi S, Sato S, Tateishi R, Fujishima T, et al. A randomized controlled trial of radiofrequency ablation with ethanol injection for small hepatocellular carcinoma. Gastroenterology. 2005;129:122–30.

  6. 6.

    Livraghi T, Meloni F, Di Stasi M, Rolle E, Solbiati L, Tinelli C, 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;47:82–9.

  7. 7.

    Poon RT, Fan ST, Lo CM, Liu CL, Ng IO, Wong J. Long-term prognosis after resection of hepatocellular carcinoma associated with hepatitis B-related cirrhosis. J Clin Oncol. 2000;18:1094–101.

  8. 8.

    Toyama T, Hiramatsu N, Yakushijin T, Oze T, Nakanishi F, Yasumaru M, et al. A new prognostic system for hepatocellular carcinoma including recurrent cases: a study of 861 patients in a single institution. J Clin Gastroenterol. 2008;42:317–22.

  9. 9.

    Adachi E, Maeda T, Matsumata T, Shirabe K, Kinukawa N, Sugimachi K, et al. Risk factors for intrahepatic recurrence in human small hepatocellular carcinoma. Gastroenterology. 1995;108:768–75.

  10. 10.

    Koike Y, Shiratori Y, Sato S, Obi S, Teratani T, Imamura M, et al. Risk factors for recurring hepatocellular carcinoma differ according to infected hepatitis virus—an analysis of 236 consecutive patients with a single lesion. Hepatology. 2000;32:1216–23.

  11. 11.

    Sasaki Y, Yamada T, Tanaka H, Ohigashi H, Eguchi H, Yano M, et al. Risk of recurrence in a long-term follow-up after surgery in 417 patients with hepatitis B- or hepatitis C-related hepatocellular carcinoma. Ann Surg. 2006;244:771–80.

  12. 12.

    Poon RT, Fan ST, Ng IO, Lo CM, Liu CL, Wong J. Different risk factors and prognosis for early and late intrahepatic recurrence after resection of hepatocellular carcinoma. Cancer. 2000;89:500–7.

  13. 13.

    Hung IF, Poon RT, Lai CL, Fung J, Fan ST, Yuen MF, et al. Recurrence of hepatitis B-related hepatocellular carcinoma is associated with high viral load at the time of resection. Am J Gastroenterol. 2008;103:1663–73.

  14. 14.

    Jang JW, Choi JY, Bae SH, Yoon SK, Woo HY, Chang UI, et al. The impact of hepatitis B viral load on recurrence after complete necrosis in patients with hepatocellular carcinoma who receive transarterial chemolipiodolization: implications for viral suppression to reduce the risk of cancer recurrence. Cancer. 2007;110:1760–7.

  15. 15.

    Huang Y, Wang Z, An S, Zhou B, Zhou Y, Chan HL, et al. Role of hepatitis B virus genotypes and quantitative HBV DNA in metastasis and recurrence of hepatocellular carcinoma. J Med Virol. 2008;80:591–7.

  16. 16.

    Dienstag JL, Perrillo RP, Schiff ER, Bartholomew M, Vicary C, Rubin M, et al. A preliminary trial of lamivudine for chronic hepatitis B infection. N Engl J Med. 1995;333:1657–61.

  17. 17.

    Dienstag JL, Goldin RD, Heathcote EJ, Hann HW, Woessner M, Stephenson SL, et al. Histological outcome during long-term lamivudine therapy. Gastroenterology. 2003;124:105–17.

  18. 18.

    Liaw YF, Sung JJ, Chow WC, Farrell G, Lee CZ, Yuen H, et al. Lamivudine for patients with chronic hepatitis B and advanced disease. N Engl J Med. 2004;351:1521–31.

  19. 19.

    Matsumoto A, Tanaka E, Rokuhara A, Kiyosawa K, Kumada H, Omata M, et al. Efficacy of lamivudine for preventing hepatocellular carcinoma in chronic hepatitis B: a multicenter retrospective study of 2795 patients. Hepatol Res. 2005;32:173–84.

  20. 20.

    Peters MG, Hann HW, Martin P, Heathcote EJ, Buggisch P, Rubin R, et al. Adefovir dipivoxil alone or in combination with lamivudine in patients with lamivudine-resistant chronic hepatitis B. Gastroenterology. 2004;126:91–101.

  21. 21.

    Chang TT, Gish RG, Hadziyannis SJ, Cianciara J, Rizzetto M, Schiff ER, et al. A dose-ranging study of the efficacy and tolerability of entecavir in lamivudine-refractory chronic hepatitis B patients. Gastroenterology. 2005;129:1198–209.

  22. 22.

    Kubo S, Tanaka H, Takemura S, Yamamoto S, Hai S, Ichikawa T, et al. Effects of lamivudine on outcome after liver resection for hepatocellular carcinoma in patients with active replication of hepatitis B virus. Hepatol Res. 2007;37:94–100.

  23. 23.

    Bruix J, Sherman M. Practice Guidelines Committee, American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma. Hepatology. 2005;42:1208–36.

  24. 24.

    Kew MC. Hepatitis viruses and hepatocellular carcinoma. Res Virol. 1998;149:257–62.

  25. 25.

    Kim CM, Koike K, Saito I, Miyamura T, Jay G. HBx gene of hepatitis B virus induces liver cancer in transgenic mice. Nature. 1991;351:317–20.

  26. 26.

    Paterlini P, Poussin K, Kew MC, Franco D, Brechot C. Selective accumulation of the X transcript of hepatitis B virus in patients negative for hepatitis B surface antigen with hepatocellular carcinoma. Hepatology. 1995;21:313–21.

  27. 27.

    Wang XW, Gibson MK, Vermeulen W, Yeh H, Forrester K, Stürzbecher HW, et al. Abrogation of p53-induced apoptosis by the hepatitis B virus X gene. Cancer Res. 1995;55:6012–6.

  28. 28.

    Yoon YJ, Chang HY, Ahn SH, Kim JK, Park YK, Kang DR, et al. MDM2 and p53 polymorphisms are associated with the development of hepatocellular carcinoma in patients with chronic hepatitis B virus infection. Carcinogenesis. 2008;29:1192–6.

  29. 29.

    Colombo M, Sangiovanni A. Etiology, natural history and treatment of hepatocellular carcinoma. Antiviral Res. 2003;60:145–50.

  30. 30.

    Pan J, Clayton M, Feitelson MA. Hepatitis B virus X antigen promotes transforming growth factor-beta1 (TGF-beta1) activity by up-regulation of TGF-beta1 and down-regulation of alpha2-macroglobulin. J Gen Virol. 2004;85:275–82.

Download references

Author information

Correspondence to Makoto Chuma.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Chuma, M., Hige, S., Kamiyama, T. et al. The influence of hepatitis B DNA level and antiviral therapy on recurrence after initial curative treatment in patients with hepatocellular carcinoma. J Gastroenterol 44, 991–999 (2009).

Download citation


  • Hepatocellular carcinoma
  • Hepatitis B virus
  • Recurrence
  • Antiviral therapy