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Surgical Outcomes of Hepatic Resection for Hepatitis B Virus Surface Antigen-Negative and Hepatitis C Virus Antibody-Negative Hepatocellular Carcinoma

  • Hepatobiliary Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

The incidence of hepatitis B virus surface antigen-negative and hepatitis C virus antibody-negative hepatocellular carcinoma (NBNC-HCC) is gradually increasing.

Methods

A retrospective cohort study was performed in 694 patients who underwent curative hepatic resection for primary HCC from January 1990 to December 2011.

Results

In the NBNC-HCC group (n = 110), the complication rate of diabetic mellitus (38 %) was significantly higher than that of the B-HCC group (n = 110; 17 %), and their rate of alcohol abuse (38 %) was significantly higher than that of both the B-HCC (26 %) and C-HCC groups (n = 474; 22 %). In the NBNC-HCC group, the tumor diameter (4.5 ± 3.6 cm) was significantly larger than that of the C-HCC group (2.9 ± 1.8 cm), but the rate of histological cirrhosis (37 %) was significantly lower than those of both the B-HCC (67 %) and C-HCC (53 %) groups. There were no significant differences regarding overall and disease-free survival among the three groups. In the NBNC-HCC group, multiple intrahepatic or distant recurrences (25 %) were significantly higher than in the C-HCC group (17 %), and the rate of recurrence more than 2 years after hepatic resection (24 %) was significantly higher than that of the B-HCC group (12 %).

Conclusions

The surgical outcomes of patients with NBNC-HCC were not significantly different compared with those of the patients with B-HCC or C-HCC. There was a substantial population with late recurrence among the patients with NBNC-HCC after curative hepatic resection, and thus not only long-term follow-up but also the early establishment of preventive methods for HCC recurrence from NBNC-hepatitis are necessary.

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References

  1. Hassoun Z, Gores GJ. Treatment of hepatocellular carcinoma. Clin Gastroenterol Hepatol. 2003;1:10–8.

    Article  PubMed  Google Scholar 

  2. Kanwal F, Hoang T, Kramer JR, Asch SM, Goetz MB, Zeringue A, Richardson P, El-Serag HB. Increasing prevalence of HCC and cirrhosis in patients with chronic hepatitis C virus infection. Gastroenterology. 2011;140:1182–8.

    Article  PubMed Central  PubMed  Google Scholar 

  3. Eun JR, Lee HJ, Kim TN, Lee KS. Risk assessment for the development of hepatocellular carcinoma: according to on-treatment viral response during long-term lamivudine therapy in hepatitis B virus-related liver disease. J Hepatol. 2010;53:118–25.

    Article  CAS  PubMed  Google Scholar 

  4. Bosetti C, Levi F, Boffetta P, Lucchini F, Negri E, La Vecchia C. Trends in mortality from hepatocellular carcinoma in Europe, 1980-2004. Hepatology. 2008;48:137–45.

    Article  PubMed  Google Scholar 

  5. Hatanaka K, Kudo M, Fukunaga T, Ueshima K, Chung H, Minami Y, Sakaguchi Y, Hagiwara S, Orino A, Osaki Y. Clinical characteristics of NonBNonC- HCC: Comparison with HBV and HCV related HCC. Intervirology. 2007;50:24–31.

    Article  PubMed  Google Scholar 

  6. El-Serag HB. Epidemiology of hepatocellular carcinoma in USA. Hepatol Res. 2007;37(Suppl 2):S88–94.

    Article  PubMed  Google Scholar 

  7. Yang JD, Harmsen WS, Slettedahl SW, Chaiteerakij R, Enders FT, Therneau TM, Orsini L, Kim WR, Roberts LR. Factors that affect risk for hepatocellular carcinoma and effects of surveillance. Clin Gastroenterol Hepatol. 2011;9:617–23.

    Article  PubMed  Google Scholar 

  8. Sasaki Y, Yamada T, Tanaka H, Ohigashi H, Eguchi H, Yano M, Ishikawa O, Imaoka S. 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 Central  PubMed  Google Scholar 

  9. Kondo K, Chijiiwa K, Funagayama M, Kai M, Otani K, Ohuchida J. Differences in long-term outcome and prognostic factors according to viral status in patients with hepatocellular carcinoma treated by surgery. J Gastrointest Surg. 2008;12:468–76.

    Article  PubMed  Google Scholar 

  10. Kaibori M, Ishizaki M, Matsui K, Kwon AH. Clinicopathologic characteristics of patients with non-B non-C hepatitis virus hepatocellular carcinoma after hepatectomy. Am J Surg. 2012;204:300–7.

    Article  PubMed  Google Scholar 

  11. Kaneda K, Kubo S, Tanaka H, Takemura S, Ohba K, Uenishi T, Kodai S, Shinkawa H, Urata Y, Sakae M, Yamamoto T, Suehiro S. Features and outcome after liver resection for non-B non-C hepatocellular carcinoma. Hepatogastroenterology. 2012;59:1889–92.

    PubMed  Google Scholar 

  12. Li T, Qin LX, Gong X, Zhou J, Sun HC, Qiu SJ, Ye QH, Wang L, Fan J. Hepatitis B virus surface antigen-negative and hepatitis C virus antibody-negative hepatocellular carcinoma: clinical characteristics, outcome, and risk factors for early and late intrahepatic recurrence after resection. Cancer. 2013;119:126–35.

    Article  CAS  PubMed  Google Scholar 

  13. Shimada M, Takenaka K, Fujiwara Y, Gion T, Shirabe K, Yanaga K, Sugimachi K. Risk factors linked to postoperative morbidity in patients with hepatocellular carcinoma. Br J Surg. 1998;85:195–8.

    Article  CAS  PubMed  Google Scholar 

  14. Yamashita Y, Taketomi A, Itoh S, Kitagawa D, Kayashima H, Harimoto N, Tsujita E, Kuroda Y, Maehara Y. Long-term favorable results of limited hepatic resections for patients with hepatocellular carcinoma: 20 years of experience. J Am Coll Surg 2007;205:19–26.

    Article  PubMed  Google Scholar 

  15. Makuuchi M, Mori T, Gunvén P, Yamazaki S, Hasegawa H. Safety of hemihepatic vascular occlusion during resection of the liver. Surg Gynecol Obstet. 1987;164:155–8.

    CAS  PubMed  Google Scholar 

  16. Clavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD, de Santibañes E, Pekolj J, Slankamenac K, Bassi C, Graf R, Vonlanthen R, Padbury R, Cameron JL, Makuuchi M. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg. 2009;250:187–96.

    Article  PubMed  Google Scholar 

  17. Yamashita Y, Shirabe K, Tsuijita E, Takeishi K, Ikegami T, Yoshizumi T, Soejima Y, Ikeda T, Utsunomiya T, Maehara Y. Third or more repeat hepatectomy for recurrent hepatocellular carcinoma. Surgery. 2013;154:1038–45.

    Article  PubMed  Google Scholar 

  18. Kanematsu T, Furuta T, Takenaka K, et al. A 5-year experience of lipiodolization: selective regional chemotherapy for 200 patients with hepatocellular carcinoma. Hepatology. 1989;10:98–102.

    Article  CAS  PubMed  Google Scholar 

  19. Toshikuni N, Izumi A, Nishino K, Inada N, Sakanoue R, Yamato R, Suehiro M, Kawanaka M, Yamada G. Comparison of outcomes between patients with alcoholic cirrhosis and those with hepatitis C virus-related cirrhosis. J Gastroenterol Hepatol. 2009;24:1276–83.

    Article  PubMed  Google Scholar 

  20. Ohira H, Abe K, Takahashi A, Zeniya M, Ichida T. Clinical features of hepatocellular carcinoma in patients with autoimmune hepatitis in Japan. J Gastroenterol. 2013;48:109–14.

    Article  PubMed  Google Scholar 

  21. Caballería L, Parés A, Castells A, Ginés A, Bru C, Rodés J. Hepatocellular carcinoma in primary biliary cirrhosis: similar incidence to that in hepatitis C virus-related cirrhosis. Am J Gastroenterol. 2001;96:1160–3.

    PubMed  Google Scholar 

  22. Moucari R1, Rautou PE, Cazals-Hatem D, Geara A, Bureau C, Consigny Y, Francoz C, Denninger MH, Vilgrain V, Belghiti J, Durand F, Valla D, Plessier A. Hepatocellular carcinoma in Budd–Chiari syndrome: characteristics and risk factors. Gut. 2008;57:828–35.

  23. Shim J, Kim BH, Kim NH, Dong SH, Kim HJ, Chang YW, Lee JI, Chang R. Clinical features of HBsAg-negative but anti-HBc-positive hepatocellular carcinoma in a hepatitis B virus endemic area. J Gastroenterol Hepatol. 2005;20:746–51.

    Article  PubMed  Google Scholar 

  24. Starley BQ, Calcagno CJ, Harrison SA. Nonalcoholic fatty liver disease and hepatocellular carcinoma: a weighty connection. Hepatology. 2010;51:1820–32.

    Article  PubMed  Google Scholar 

  25. Shirabe K, Toshima T, Taketomi A, Taguchi K, Yoshizumi T, Uchiyama H, Harimoto N, Kajiyama K, Egashira A, Maehara Y. Hepatic aflatoxin B1-DNA adducts and TP53 mutations in patients with hepatocellular carcinoma despite low exposure to aflatoxin B1 in southern Japan. Liver Int. 2011;31:1366–72.

    Article  CAS  PubMed  Google Scholar 

  26. Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med. 2003;348:1625–38.

    Article  PubMed  Google Scholar 

  27. Welzel TM, Graubard BI, Quraishi S, Zeuzem S, Davila JA, El-Serag HB, McGlynn KA. Population-attributable fractions of risk factors for hepatocellular carcinoma in the United States. Am J Gastroenterol. 2013;108:1314–21.

    Article  PubMed Central  PubMed  Google Scholar 

  28. Noguchi K, Nakashima O, Nakashima Y, Shiota K, Nawata H, Kojiro M. Clinicopathologic study on hepatocellular carcinoma negative for hepatitis B surface antigen and antibody to hepatitis C virus. Int J Mol Med. 2000;6:661–5.

  29. Sakamoto M, Hirohashi S, Shimosato Y. Early stages of multistep hepatocarcinogenesis: adenomatous hyperplasia and early hepatocellular carcinoma. Hum Pathol. 1991;22:172–8.

    Article  CAS  PubMed  Google Scholar 

  30. Theise ND, Marcelin K, Goldfischer M, Hytiroglou P, Ferrell L, Thung SN. Low proliferative activity in macroregenerative nodules: evidence for an alternate hypothesis concerning human hepatocarcinogenesis. Liver. 1996;16:134–9.

    Article  CAS  PubMed  Google Scholar 

  31. Taketomi A, Kitagawa D, Itoh S, Harimoto N, Yamashita Y, Gion T, Shirabe K, Shimada M, Maehara Y. Trends in morbidity and mortality after hepatic resection for hepatocellular carcinoma: an institute’s experience with 625 patients. J Am Coll Surg. 2007;204:580–7.

    Article  PubMed  Google Scholar 

  32. Takaki A, Kawai D, Yamamoto K. Multiple hits, including oxidative stress, as pathogenesis and treatment target in non-alcoholic steatohepatitis (NASH). Int J Mol Sci. 2013;14:20704–28.

    Article  PubMed Central  PubMed  Google Scholar 

  33. Kawai D, Takaki A, Nakatsuka A, Wada J, Tamaki N, Yasunaka T, Koike K, Tsuzaki R, Matsumoto K, Miyake Y, Shiraha H, Morita M, Makino H, Yamamoto K. Hydrogen-rich water prevents progression of nonalcoholic steatohepatitis and accompanying hepatocarcinogenesis in mice. Hepatology. 2012;56:912–21.

    Article  CAS  PubMed  Google Scholar 

  34. Stefanska J, Pawliczak R. Apocynin: molecular aptitudes. Mediators Inflamm. 2008;2008:106507. doi:10.1155/2008/106507.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Yoshimoto S, Loo TM, Atarashi K, Kanda H, Sato S, Oyadomari S, Iwakura Y, Oshima K, Morita H, Hattori M, Honda K, Ishikawa Y, Hara E, Ohtani N. Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature. 2013;499:97–101.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgment

This study was partly funded by a Grant-in-Aid (No. 25462093) from the Ministry of Education, Science, and Culture in Japan.

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Authors and Affiliations

  1. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Yo-ichi Yamashita MD, PhD, Daisuke Imai MD, Yuki Bekki MD, Koichi Kimura MD, Yoshiriro Matsumoto MD, Hidekazu Nakagawara MD, Toru Ikegami MD, PhD, Tomoharu Yoshizumi MD, PhD, Ken Shirabe MD, PhD & Yoshihiko Maehara MD, PhD, FACS

  2. Pathology & Microbiology, Saga University, Saga, Japan

    Shinichi Aishima MD, PhD

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  1. Yo-ichi Yamashita MD, PhD
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  2. Daisuke Imai MD
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  11. Yoshihiko Maehara MD, PhD, FACS
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Correspondence to Yo-ichi Yamashita MD, PhD.

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Yamashita, Yi., Imai, D., Bekki, Y. et al. Surgical Outcomes of Hepatic Resection for Hepatitis B Virus Surface Antigen-Negative and Hepatitis C Virus Antibody-Negative Hepatocellular Carcinoma. Ann Surg Oncol 22, 2279–2285 (2015). https://doi.org/10.1245/s10434-014-4261-x

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  • DOI: https://doi.org/10.1245/s10434-014-4261-x

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