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High Hepatitis B Viral Load Predicts Recurrence of Small Hepatocellular Carcinoma after Curative Resection

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Journal of Gastrointestinal Surgery Aims and scope

Abstract

A retrospective cohort study was conducted to identify risk factors for recurrence of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative resection. A total of 317 patients who had received curative resection of pathologically proven small HCC (≤3 cm in diameter) were analyzed to ascertain the factors affecting recurrence. The median follow-up period was 33.7 months. Cumulative recurrence rates at 1, 3, and 5 years after resection were 23.5%, 49.5%, and 65.5%, respectively. Male sex, alpha-fetoprotein (AFP) ≥400 ng/mL, HBV DNA level ≥4 log10 copies/mL, prolonged prothrombin time, tumor size ≥2 cm, microvascular invasion, absence of capsular formation, moderate/poor tumor differentiation, and absence of postoperative interferon-alpha (IFN-α) treatment were associated with increased cumulative risk of HCC recurrence. By multivariate analysis, HBV DNA level ≥4 log10 copies/mL (P < 0.001, hazard ratio (HR) 2.110), AFP ≥400 ng/mL (P = 0.011, HR 1.574), microvascular invasion (P < 0.001, HR 1.767), and postoperative IFN-α treatment (P = 0.022, HR 0.562) remained to be independently associated with HCC recurrence. Those contributing to late recurrence (>2 years) were older age and HBV DNA level ≥4 log10 copies/mL. Patients with persistent HBV DNA level ≥4 log10 copies/mL at resection and follow-up had the highest recurrence risk (P < 0.001, HR 4.129). HBV DNA level ≥4 log10 copies/mL at the time of resection was the most important risk factor for recurrence. Postoperative IFN-α treatment significantly decreased the recurrence risk after resection.

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References

  1. Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet 2003;362:1907-1917.

    Article  PubMed  Google Scholar 

  2. Takayama T, Makuuchi M, Hirohashi S, Sakamoto M, Yamamoto J, Shimada K, Kosuge T, Okada S, Takayasu K, Yamasaki S. Early hepatocellular carcinoma as an entity with a high rate of surgical cure. Hepatology 1998;28:1241-1246.

    Article  CAS  PubMed  Google Scholar 

  3. Zhang BH, Yang BH, Tang ZY. Randomized controlled trial of screening for hepatocellular carcinoma. J Cancer Res Clin Oncol 2004;130:417-422.

    PubMed  Google Scholar 

  4. Adachi E, Maeda T, Matsumata T, Shirabe K, Kinukawa N, Sugimachi K, Tsuneyoshi M. Risk factors for intrahepatic recurrence in human small hepatocellular carcinoma. Gastroenterology 1995;108:768-775.

    Article  CAS  PubMed  Google Scholar 

  5. Takayama T, Sekine T, Makuuchi M, Yamasaki S, Kosuge T, Yamamoto J, Shimada K, Sakamoto M, Hirohashi S, Ohashi Y, Kakizoe T. Adoptive immunotherapy to lower postsurgical recurrence rates of hepatocellular carcinoma: a randomised trial. Lancet 2000;356:802-807.

    Article  CAS  PubMed  Google Scholar 

  6. Shah SA, Cleary SP, Wei AC, Yang I, Taylor BR, Hemming AW, Langer B, Grant DR, Greig PD, Gallinger S. Recurrence after liver resection for hepatocellular carcinoma: risk factors, treatment, and outcomes. Surgery 2007;141:330-339.

    Article  PubMed  Google Scholar 

  7. Ohkubo T, Yamamoto J, Sugawara Y, Shimada K, Yamasaki S, Makuuchi M, Kosuge T. Surgical results for hepatocellular carcinoma with macroscopic portal vein tumor thrombosis. J Am Coll Surg 2000;191:657-660.

    Article  CAS  PubMed  Google Scholar 

  8. Schoniger-Hekele M, Muller C, Kutilek M, Oesterreicher C, Ferenci P, Gangl A. Hepatocellular carcinoma in Central Europe: prognostic features and survival. Gut 2001;48:103-109.

    Article  CAS  PubMed  Google Scholar 

  9. Tung-Ping Poon R, Fan ST, Wong J. Risk factors, prevention, and management of postoperative recurrence after resection of hepatocellular carcinoma. Ann Surg 2000;232:10-24

    Article  CAS  PubMed  Google Scholar 

  10. Utsunomiya T, Shimada M, Taguchi KI, Hasegawa H, Yamashita Y, Hamatsu T, Aishima SI, Sugimachi K. Clinicopathologic features and postoperative prognosis of multicentric small hepatocellular carcinoma. J Am Coll Surg 2000;190:331-335.

    Article  CAS  PubMed  Google Scholar 

  11. Iloeje UH, Yang HI, Su J, Jen CL, You SL, Chen CJ. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology 2006;130:678-686.

    Article  PubMed  Google Scholar 

  12. Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, Huang GT, Iloeje UH. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. Jama 2006;295:65-73.

    Article  CAS  PubMed  Google Scholar 

  13. Hung IF, Poon RT, Lai CL, Fung J, Fan ST, Yuen MF. Recurrence of hepatitis B-related hepatocellular carcinoma is associated with high viral load at the time of resection. Am J Gastroenterol 2008;103:1663-1673.

    Article  PubMed  Google Scholar 

  14. Wu JC, Huang YH, Chau GY, Su CW, Lai CR, Lee PC, Huo TI, Sheen IJ, Lee SD, Lui WY. Risk factors for early and late recurrence in hepatitis B-related hepatocellular carcinoma. J Hepatol 2009;51:890-897.

    Article  PubMed  Google Scholar 

  15. Edmondson HA, Steiner PE. Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies. Cancer 1954;7:462-503.

    Article  CAS  PubMed  Google Scholar 

  16. Imamura H, Matsuyama Y, Tanaka E, Ohkubo T, Hasegawa K, Miyagawa S, Sugawara Y, Minagawa M, Takayama T, Kawasaki S, Makuuchi M. Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy. J Hepatol 2003;38:200-207.

    Article  PubMed  Google Scholar 

  17. 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;18:1094-1101.

    CAS  PubMed  Google Scholar 

  18. 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;89:500-507.

    Article  CAS  PubMed  Google Scholar 

  19. Kubo S, Hirohashi K, Tanaka H, Tsukamoto T, Shuto T, Higaki I, Takemura S, Yamamoto T, Nishiguchi S, Kinoshita H. Virologic and biochemical changes and prognosis after liver resection for hepatitis B virus-related hepatocellular carcinoma. Dig Surg 2001;18:26-33.

    Article  CAS  PubMed  Google Scholar 

  20. Wang ZL, Liang P, Dong BW, Yu XL, Yu de J. Prognostic factors and recurrence of small hepatocellular carcinoma after hepatic resection or microwave ablation: a retrospective study. J Gastrointest Surg 2008;12:327-337.

    Article  PubMed  Google Scholar 

  21. Chen YJ, Yeh SH, Chen JT, Wu CC, Hsu MT, Tsai SF, Chen PJ, Lin CH. Chromosomal changes and clonality relationship between primary and recurrent hepatocellular carcinoma. Gastroenterology 2000;119:431-440.

    Article  CAS  PubMed  Google Scholar 

  22. Chu CJ, Hussain M, Lok AS. Quantitative serum HBV DNA levels during different stages of chronic hepatitis B infection. Hepatology 2002;36:1408-1415.

    CAS  PubMed  Google Scholar 

  23. Chan HL, Sung JJ. Hepatocellular carcinoma and hepatitis B virus. Semin Liver Dis 2006;26:153-161.

    Article  CAS  PubMed  Google Scholar 

  24. Colombo M, Sangiovanni A. Etiology, natural history and treatment of hepatocellular carcinoma. Antiviral Res 2003;60:145-150.

    Article  CAS  PubMed  Google Scholar 

  25. 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;85:275-282.

    Article  CAS  PubMed  Google Scholar 

  26. Volpes R, Van Den Oord JJ, Desmet VJ. Vascular adhesion molecules in acute and chronic liver inflammation. Hepatology 1992;15:269-275.

    Article  CAS  PubMed  Google Scholar 

  27. von Marschall Z, Scholz A, Cramer T, Schafer G, Schirner M, Oberg K, Wiedenmann B, Hocker M, Rosewicz S. Effects of interferon alpha on vascular endothelial growth factor gene transcription and tumor angiogenesis. J Natl Cancer Inst 2003;95:437-448.

    Article  Google Scholar 

  28. Wang L, Wu WZ, Sun HC, Wu XF, Qin LX, Liu YK, Liu KD, Tang ZY. Mechanism of interferon alpha on inhibition of metastasis and angiogenesis of hepatocellular carcinoma after curative resection in nude mice. J Gastrointest Surg 2003;7:587-594.

    Article  PubMed  Google Scholar 

  29. Ikai I, Arii S, Kojiro M, Ichida T, Makuuchi M, Matsuyama Y, Nakanuma Y, Okita K, Omata M, Takayasu K, Yamaoka Y. Reevaluation of prognostic factors for survival after liver resection in patients with hepatocellular carcinoma in a Japanese nationwide survey. Cancer 2004;101:796-802.

    Article  PubMed  Google Scholar 

  30. Sumie S, Kuromatsu R, Okuda K, Ando E, Takata A, Fukushima N, Watanabe Y, Kojiro M, Sata M. Microvascular invasion in patients with hepatocellular carcinoma and its predictable clinicopathological factors. Ann Surg Oncol 2008;15:1375-1382.

    Article  PubMed  Google Scholar 

  31. Tangkijvanich P, Anukulkarnkusol N, Suwangool P, Lertmaharit S, Hanvivatvong O, Kullavanijaya P, Poovorawan Y. Clinical characteristics and prognosis of hepatocellular carcinoma: analysis based on serum alpha-fetoprotein levels. J Clin Gastroenterol 2000;31:302-308.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank Professor Nai-qing Zhao, Shanghai Medical College, Fudan University, China, for guide in the statistical analysis.

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, 180# Fenglin Road, Shanghai, 200032, China

    Li-Shuai Qu, Fei Jin & Xi-Zhong Shen

  2. Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China

    Xiao-Wu Huang

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  1. Li-Shuai Qu
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  2. Fei Jin
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Correspondence to Xi-Zhong Shen.

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Financial support

This study was financially supported by The National High Technology Research and Development Program of China 863 Project (No. 2006AA02Z4C5) and China National Key Projects for Infectious Diseases (2008ZX10002-017).

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Qu, LS., Jin, F., Huang, XW. et al. High Hepatitis B Viral Load Predicts Recurrence of Small Hepatocellular Carcinoma after Curative Resection. J Gastrointest Surg 14, 1111–1120 (2010). https://doi.org/10.1007/s11605-010-1211-1

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  • DOI: https://doi.org/10.1007/s11605-010-1211-1

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