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

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
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Abstract

Background

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.

Methods

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).

Results

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.

Conclusion

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.

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References

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

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Gastroenterology and Hematology, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo, 060-8638, Japan

    Makoto Chuma, Shuhei Hige, Mitsuru Nakanishi, Toshihisa Kohara, Takuya Sho, Keiko Yamamoto, Hiromasa Horimoto, Tomoe Kobayashi & Masahiro Asaka

  2. Department of General Surgery, Hokkaido University, Sapporo, Japan

    Toshiya Kamiyama, Kazuaki Nakanishi, Hideki Yokoo, Michiaki Matsushita & Satoru Todo

  3. Department of Internal Medicine, Hokkaido Gastroenterology Hospital, Sapporo, Japan

    Takashi Meguro

  4. Department of Gastroenterology, Sapporo Municipal Hospital, Sapporo, Japan

    Atsushi Nagasaka

  5. Department of Gastroenterology, Hakodate Municipal Hospital, Hakodate, Japan

    Yoshiya Yamamoto

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  1. Makoto Chuma
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Correspondence to Makoto Chuma.

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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). https://doi.org/10.1007/s00535-009-0093-z

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  • DOI: https://doi.org/10.1007/s00535-009-0093-z

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