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Published in: Hepatology International 3/2011

01-09-2011 | Original Article

Influence of serum HBV DNA load on recurrence of hepatocellular carcinoma after treatment with percutaneous radiofrequency ablation

Authors: Tadashi Goto, Haruhiko Yoshida, Ryosuke Tateishi, Kenichiro Enooku, Eriko Goto, Takahisa Sato, Takamasa Ohki, Ryota Masuzaki, Jun Imamura, Shuichiro Shiina, Kazuhiko Koike, Masao Omata

Published in: Hepatology International | Issue 3/2011

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Abstract

Background

High serum load of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) is a strong risk factor of hepatocellular carcinoma (HCC) development, independent of hepatitis B e antigen, serum alanine aminotransferase level, and liver cirrhosis. We evaluated whether serum HBV DNA load is associated with the risk of recurrence of HBV-related HCC treated with radiofrequency ablation (RFA).

Methods

The study population was 69 consecutive patients with HBV-related HCC treated locally completely with RFA between January 2000 and September 2007. The risk factors for HCC recurrence were analyzed based on laboratory data, including serum HBV DNA load, together with tumor size and number using univariate and multivariate proportional hazard regression analyses.

Results

HCC recurrence was observed in 42 of 69 patients during the median observation period of 1.5 years. Cumulative recurrence rates at 1, 3, and 5 years were 26.5, 57.8, and 74.3%, respectively. In univariate analysis, albumin (<3.5 g/dl), platelet count (<150 × 103/mm3), prothrombin activity (PT) (<70%), Child-Pugh class B, serum HBV DNA load (>4.0 log10 copies/ml), and tumor number (>3) were associated with the recurrence at p ≤ 0.15. Multivariate Cox regression analysis with stepwise variable selection showed that the tumor number (risk ratio, 4.63; 95% CI, 1.50–14.25, P = 0.0076), low PT (3.39, 1.52–5.78, P = 0.0029), and high HBV DNA load (2.67, 1.16–6.14, P = 0.021) were independent risk factors for HCC recurrence.

Conclusion

Serum HBV DNA load is associated with the risk of recurrence of HBV-related HCC after RFA.
Literature
1.
go back to reference Lavanchy D. Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat 2004;11:97–107PubMedCrossRef Lavanchy D. Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat 2004;11:97–107PubMedCrossRef
2.
go back to reference Shiratori Y, Shiina S, Zhang PY, Ohno E, Okudaira T, Payawal DA, Ono-Nita SK, Imamura M, Kato N, Omata M. Does dual infection by hepatitis B and C viruses play an important role in the pathogenesis of hepatocellular carcinoma in Japan? Cancer 1997;80:2060–2067PubMedCrossRef Shiratori Y, Shiina S, Zhang PY, Ohno E, Okudaira T, Payawal DA, Ono-Nita SK, Imamura M, Kato N, Omata M. Does dual infection by hepatitis B and C viruses play an important role in the pathogenesis of hepatocellular carcinoma in Japan? Cancer 1997;80:2060–2067PubMedCrossRef
4.
go back to reference Beasley RP. Hepatitis B virus. The major etiology of hepatocellular carcinoma. Cancer 1988;61:1942–1956PubMedCrossRef Beasley RP. Hepatitis B virus. The major etiology of hepatocellular carcinoma. Cancer 1988;61:1942–1956PubMedCrossRef
6.
go back to reference Imazeki F, Omata M, Yokosuka O, Okuda K. Integration of hepatitis B virus DNA in hepatocellular carcinoma. Cancer 1986;58:1055–1060PubMedCrossRef Imazeki F, Omata M, Yokosuka O, Okuda K. Integration of hepatitis B virus DNA in hepatocellular carcinoma. Cancer 1986;58:1055–1060PubMedCrossRef
7.
go back to reference Br′echot C. Hepatitis B virus (HBV) and hepatocellular carcinoma. HBV DNA status and its implications. J Hepatol 1987;4:269–279CrossRef Br′echot C. Hepatitis B virus (HBV) and hepatocellular carcinoma. HBV DNA status and its implications. J Hepatol 1987;4:269–279CrossRef
8.
go back to reference Br′echot C, Gozuacik D, Murakami Y, Paterlini-Bréchot P. Molecular bases for the development of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Semin Cancer Biol 2000;10:211–231CrossRef Br′echot C, Gozuacik D, Murakami Y, Paterlini-Bréchot P. Molecular bases for the development of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Semin Cancer Biol 2000;10:211–231CrossRef
9.
go back to reference Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, Huang GT, Iloeje UH, REVEAL-HBV Study Group. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA 2006;295:65–73PubMedCrossRef Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, Huang GT, Iloeje UH, REVEAL-HBV Study Group. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA 2006;295:65–73PubMedCrossRef
10.
go back to reference Liaw YF, Sung JJ, Chow WC, Farrell G, Lee CZ, Yuen H, Tanwandee T, Tao QM, Shue K, Keene ON, Dixon JS, Gray DF, Sabbat J, Cirrhosis Asian Lamivudine Multicentre Study Group. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med 2004;351:1521–1531PubMedCrossRef Liaw YF, Sung JJ, Chow WC, Farrell G, Lee CZ, Yuen H, Tanwandee T, Tao QM, Shue K, Keene ON, Dixon JS, Gray DF, Sabbat J, Cirrhosis Asian Lamivudine Multicentre Study Group. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med 2004;351:1521–1531PubMedCrossRef
11.
go back to reference Poon RT, Fan ST, Lo CM, Ng IO, Liu CL, Lam CM, Wong J. Improving survival results after resection of hepatocellular carcinoma A prospective study of 377 patients. Ann Surg 2001;234:63–70PubMedCrossRef Poon RT, Fan ST, Lo CM, Ng IO, Liu CL, Lam CM, Wong J. Improving survival results after resection of hepatocellular carcinoma A prospective study of 377 patients. Ann Surg 2001;234:63–70PubMedCrossRef
12.
go back to reference Shiina S, Teratani T, Obi S, Sato S, Tateishi R, Fujishima T, Ishikawa T, Koike Y, Yoshida H, Kawabe T, Omata M. A randomized controlled trial of radiofrequency ablation with ethanol injection for small hepatocellular carcinoma. Gastroenterology 2005;129:122–30PubMedCrossRef Shiina S, Teratani T, Obi S, Sato S, Tateishi R, Fujishima T, Ishikawa T, Koike Y, Yoshida H, Kawabe T, Omata M. A randomized controlled trial of radiofrequency ablation with ethanol injection for small hepatocellular carcinoma. Gastroenterology 2005;129:122–30PubMedCrossRef
13.
go back to reference Waki K, Aikata H, Katamura Y, Kawaoka T, Takaki S, Hiramatsu A, Takahashi S, Toyota N, Ito K, Chayama K. Percutaneous radiofrequency ablation as first-line treatment for small hepatocellular carcinoma: results and prognostic factors on long-term follow up. J Gastroenterol Hepatol 2010;25:597–604PubMedCrossRef Waki K, Aikata H, Katamura Y, Kawaoka T, Takaki S, Hiramatsu A, Takahashi S, Toyota N, Ito K, Chayama K. Percutaneous radiofrequency ablation as first-line treatment for small hepatocellular carcinoma: results and prognostic factors on long-term follow up. J Gastroenterol Hepatol 2010;25:597–604PubMedCrossRef
14.
go back to reference N’Kontchou G, Mahamoudi A, Aout M, Ganne-Carrié N, Grando V, Coderc E, Vicaut E, Trinchet JC, Sellier N, Beaugrand M, Seror O. Radiofrequency ablation of hepatocellular carcinoma: Long-term results and prognostic factors in 235 Western patients with cirrhosis. Hepatology 2009;50:1475–83PubMedCrossRef N’Kontchou G, Mahamoudi A, Aout M, Ganne-Carrié N, Grando V, Coderc E, Vicaut E, Trinchet JC, Sellier N, Beaugrand M, Seror O. Radiofrequency ablation of hepatocellular carcinoma: Long-term results and prognostic factors in 235 Western patients with cirrhosis. Hepatology 2009;50:1475–83PubMedCrossRef
15.
go back to reference Zerbini A, Pilli M, Laccabue D, Pelosi G, Molinari A, Negri E, Cerioni S, Fagnoni F, Soliani P, Ferrari C, Missale G. Radiofrequency thermal ablation for hepatocellular carcinoma stimulates autologous NK-cell response. Gastroenterology 2010;138:1931–1942PubMedCrossRef Zerbini A, Pilli M, Laccabue D, Pelosi G, Molinari A, Negri E, Cerioni S, Fagnoni F, Soliani P, Ferrari C, Missale G. Radiofrequency thermal ablation for hepatocellular carcinoma stimulates autologous NK-cell response. Gastroenterology 2010;138:1931–1942PubMedCrossRef
16.
go back to reference Kim CM, Koike K, Saito I, Miyamura T, Jay G. HBx gene of hepatitis B virus induces liver cancer in transgenic mice. Nature 1991;251:317–320CrossRef Kim CM, Koike K, Saito I, Miyamura T, Jay G. HBx gene of hepatitis B virus induces liver cancer in transgenic mice. Nature 1991;251:317–320CrossRef
17.
go back to reference Koike K, Tsutsumi T, Fujie H, Shintani Y, Kyoji M. Molecular mechanism of viral hepatocarcinogenesis. Oncology 2002;62(Suppl 1):29–37PubMedCrossRef Koike K, Tsutsumi T, Fujie H, Shintani Y, Kyoji M. Molecular mechanism of viral hepatocarcinogenesis. Oncology 2002;62(Suppl 1):29–37PubMedCrossRef
18.
go back to reference Tateishi R, Shiina S, Teratani T, Obi S, Sato S, Koike Y, Fujishima T, Yoshida H, Kawabe T, Omata M. Percutaneous radiofrequency ablation for hepatocellular carcinoma. An analysis of 1,000 cases. Cancer 2005;103:1201–1209PubMedCrossRef Tateishi R, Shiina S, Teratani T, Obi S, Sato S, Koike Y, Fujishima T, Yoshida H, Kawabe T, Omata M. Percutaneous radiofrequency ablation for hepatocellular carcinoma. An analysis of 1,000 cases. Cancer 2005;103:1201–1209PubMedCrossRef
19.
go back to reference Huang GT, Lee PH, Tsang YM, Lai MY, Yang PM, Hu RH, Chen PJ, Kao JH, Sheu JC, Lee CZ, Chen DS. Percutaneous ethanol injection versus surgical resection for the treatment of small hepatocellular carcinoma: a prospective study. Ann Surg 2005;242:36–42PubMedCrossRef Huang GT, Lee PH, Tsang YM, Lai MY, Yang PM, Hu RH, Chen PJ, Kao JH, Sheu JC, Lee CZ, Chen DS. Percutaneous ethanol injection versus surgical resection for the treatment of small hepatocellular carcinoma: a prospective study. Ann Surg 2005;242:36–42PubMedCrossRef
20.
go back to reference Chen MS, Li JQ, Zheng Y, Guo RP, Liang HH, Zhang YQ, Lin XJ, Lau WY. A prospective randomized trial comparing percutaneous local ablative therapy and partial hepatectomy for small hepatocellular carcinoma. Ann Surg 2006;243:321–328PubMedCrossRef Chen MS, Li JQ, Zheng Y, Guo RP, Liang HH, Zhang YQ, Lin XJ, Lau WY. A prospective randomized trial comparing percutaneous local ablative therapy and partial hepatectomy for small hepatocellular carcinoma. Ann Surg 2006;243:321–328PubMedCrossRef
21.
go back to reference Torzilli G, Minagawa M, Takayama T, Inoue K, Hui AM, Kubota K, Ohtomo K, Makuuchi M. Accurate preoperative evaluation of liver mass lesions without fine-needle biopsy. Hepatology 1999;30:889–893PubMedCrossRef Torzilli G, Minagawa M, Takayama T, Inoue K, Hui AM, Kubota K, Ohtomo K, Makuuchi M. Accurate preoperative evaluation of liver mass lesions without fine-needle biopsy. Hepatology 1999;30:889–893PubMedCrossRef
22.
go back to reference Edmondson HA, Steiner PE. Primary carcinoma of the liver: a study of 100 cases among 4,900 necropsies. Cancer 1954;7:462–503PubMedCrossRef Edmondson HA, Steiner PE. Primary carcinoma of the liver: a study of 100 cases among 4,900 necropsies. Cancer 1954;7:462–503PubMedCrossRef
23.
go back to reference Desmet VJ, Gerber M, Hoofnagle JH, Manns M, Sheuer PJ. Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology 1994;19:1513–1520PubMedCrossRef Desmet VJ, Gerber M, Hoofnagle JH, Manns M, Sheuer PJ. Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology 1994;19:1513–1520PubMedCrossRef
24.
go back to reference Omata M, Tateishi R, Yoshida H, Shiina S. Treatment of hepatocellular carcinoma by percutaneous tumor ablation methods: ethanol injection therapy and radiofrequency ablation. Gastroenterology 2004;127:S159–166PubMedCrossRef Omata M, Tateishi R, Yoshida H, Shiina S. Treatment of hepatocellular carcinoma by percutaneous tumor ablation methods: ethanol injection therapy and radiofrequency ablation. Gastroenterology 2004;127:S159–166PubMedCrossRef
25.
go back to reference Kubo S, Hirohashi K, Tanaka H, Tsukamoto T, Shuto T, Yamamoto T, Ikebe T, Wakasa K, Nishiguchi S, Kinoshita H. Effect of viral status on recurrence after liver resection for patients with hepatitis B virus-related hepatocellular carcinoma. Cancer 2000;88:1016–1024PubMedCrossRef Kubo S, Hirohashi K, Tanaka H, Tsukamoto T, Shuto T, Yamamoto T, Ikebe T, Wakasa K, Nishiguchi S, Kinoshita H. Effect of viral status on recurrence after liver resection for patients with hepatitis B virus-related hepatocellular carcinoma. Cancer 2000;88:1016–1024PubMedCrossRef
26.
go back to reference Yang HI, Lu SN, Liaw YF, You SL, Sun CA, Wang LY, Hsiao CK, Chen PJ, Chen DS, Chen CJ, Taiwan Community-Based Cancer Screening Project Group. Hepatitis B e antigen and the risk of hepatocellular carcinoma. N Engl J Med 2002;347:168–174PubMedCrossRef Yang HI, Lu SN, Liaw YF, You SL, Sun CA, Wang LY, Hsiao CK, Chen PJ, Chen DS, Chen CJ, Taiwan Community-Based Cancer Screening Project Group. Hepatitis B e antigen and the risk of hepatocellular carcinoma. N Engl J Med 2002;347:168–174PubMedCrossRef
27.
go back to reference Sherman M. Hepatocellular carcinoma: epidemiology, risk factors, and screening. Semin Liver Dis 2005;25:143–154PubMedCrossRef Sherman M. Hepatocellular carcinoma: epidemiology, risk factors, and screening. Semin Liver Dis 2005;25:143–154PubMedCrossRef
28.
go back to reference Yuen MF, Yuan HJ, Wong DK, Yuen JC, Wong WM, Chan AO, Wong BC, Lai KC, Lai CL. Prognostic determinants for chronic hepatitis B in Asians: therapeutic implications. Gut 2005;54:1610–1614PubMedCrossRef Yuen MF, Yuan HJ, Wong DK, Yuen JC, Wong WM, Chan AO, Wong BC, Lai KC, Lai CL. Prognostic determinants for chronic hepatitis B in Asians: therapeutic implications. Gut 2005;54:1610–1614PubMedCrossRef
29.
go back to reference de Franchis R, Hadengue A, Lau G, Lavanchy D, Lok A, McIntyre N, Mele A, Paumgartner G, Pietrangelo A, Rodés J, Rosenberg W, Valla D, EASL Jury. EASL international consensus conference on hepatitis B. 13–14 September, 2002: Geneva, Switzerland. Consensus statement (long version). J Hepatol 2003;39:S3–25PubMed de Franchis R, Hadengue A, Lau G, Lavanchy D, Lok A, McIntyre N, Mele A, Paumgartner G, Pietrangelo A, Rodés J, Rosenberg W, Valla D, EASL Jury. EASL international consensus conference on hepatitis B. 13–14 September, 2002: Geneva, Switzerland. Consensus statement (long version). J Hepatol 2003;39:S3–25PubMed
30.
go back to reference ACT-HBV Asia-Pacific Steering Committee Members. Chronic hepatitis B: treatment alert. Liver Int 2006;26:47–58CrossRef ACT-HBV Asia-Pacific Steering Committee Members. Chronic hepatitis B: treatment alert. Liver Int 2006;26:47–58CrossRef
31.
go back to reference Yoshida H, Yoshida H, Goto E, Sato T, Ohki T, Masuzaki R, Tateishi R, Goto T, Shiina S, Kawabe T, Omata M. Safety and efficacy of lamivudine after radiofrequency ablation in patients with hepatitis B virus-related hepatocellular carcinoma. Hepotol Int 2008;2:89–94CrossRef Yoshida H, Yoshida H, Goto E, Sato T, Ohki T, Masuzaki R, Tateishi R, Goto T, Shiina S, Kawabe T, Omata M. Safety and efficacy of lamivudine after radiofrequency ablation in patients with hepatitis B virus-related hepatocellular carcinoma. Hepotol Int 2008;2:89–94CrossRef
32.
go back to reference Sumi H, Yokosuka O, Seki N, Arai M, Imazeki F, Kurihara T, Kanda T, Fukai K, Kato M, Saisho H. Influence of hepatitis B virus genotypes on the progression of chronic type B liver disease. Hepatology 2003;37:19–26PubMedCrossRef Sumi H, Yokosuka O, Seki N, Arai M, Imazeki F, Kurihara T, Kanda T, Fukai K, Kato M, Saisho H. Influence of hepatitis B virus genotypes on the progression of chronic type B liver disease. Hepatology 2003;37:19–26PubMedCrossRef
33.
go back to reference Orito E, Mizokami M. Hepatitis B virus genotypes and hepatocellular carcinoma in Japan. Intervirology 2003;46:408–12PubMedCrossRef Orito E, Mizokami M. Hepatitis B virus genotypes and hepatocellular carcinoma in Japan. Intervirology 2003;46:408–12PubMedCrossRef
34.
go back to reference Chen JD, Liu CJ, Lee PH, Chen PJ, Lai MY, Kao JH, Chen DS. Hepatitis B genotypes correlate with tumor recurrence after curative resection of hepatocellular carcinoma. Clin Gastroenterol Hepatol 2004;2:64–71PubMedCrossRef Chen JD, Liu CJ, Lee PH, Chen PJ, Lai MY, Kao JH, Chen DS. Hepatitis B genotypes correlate with tumor recurrence after curative resection of hepatocellular carcinoma. Clin Gastroenterol Hepatol 2004;2:64–71PubMedCrossRef
Metadata
Title
Influence of serum HBV DNA load on recurrence of hepatocellular carcinoma after treatment with percutaneous radiofrequency ablation
Authors
Tadashi Goto
Haruhiko Yoshida
Ryosuke Tateishi
Kenichiro Enooku
Eriko Goto
Takahisa Sato
Takamasa Ohki
Ryota Masuzaki
Jun Imamura
Shuichiro Shiina
Kazuhiko Koike
Masao Omata
Publication date
01-09-2011
Publisher
Springer-Verlag
Published in
Hepatology International / Issue 3/2011
Print ISSN: 1936-0533
Electronic ISSN: 1936-0541
DOI
https://doi.org/10.1007/s12072-011-9255-1

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