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Clinical Characteristics and Surgical Outcome in Hepatocellular Carcinoma without Hepatitis B Virus Surface Antigen or Hepatitis C Virus Antibody

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Abstract

Objective

We investigated clinical characteristics and surgical outcome of hepatocellular carcinoma in association with hepatitis viral status.

Summary Background Data

No consensus exists concerning differences in surgical outcome in patients with hepatocellular carcinoma according to viral hepatitis status, especially those negative for hepatitis B virus surface antigen and antibody to hepatitis C virus.

Methods

Clinicopathologic data were available for 39 hepatectomy patients with hepatocellular carcinoma who were negative for hepatitis B virus surface antigen and hepatitis C virus antibody. Clinical characteristics and surgical outcome were analyzed retrospectively and compared to those patients with positive hepatitis viral markers.

Results

Patients negative for viral hepatitis markers were more likely to have large, advanced-stages tumors with relatively well-preserved liver function and had a lower incidence of intrahepatic recurrences (P = 0.009). The intrahepatic recurrence rate reached a plateau at approximately 3 years after resection in patients with negative viral markers, while it continued to increase steadily in patients positive for viral hepatitis markers. By multivariable analysis, the absence of viral hepatitis markers predicted a decreased rate of intrahepatic recurrence (relative risk, 0.222; P = 0.001).

Conclusions

Adequate surgical resection in hepatocellular carcinoma patients negative for viral markers offers a good survival benefit, regardless of the etiology of the hepatocellular carcinoma.

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Abbreviations

AFP:

α-fetoprotein

AWD:

alive with disease

BMI:

body mass index

CLIP:

Cancer of the Liver Italian Program

DFD:

died from the disease

DOD:

died from other diseases

HA:

hyaluronic acid

HBcAb:

anti-HB core antibody

HBsAg:

hepatitis B virus surface antigen

HBV:

hepatitis B virus

HCC:

hepatocellular carcinoma

HCV:

hepatitis C virus

HCVAb:

hepatitis C virus antibody

ICGR15:

indocyanine green retention rate at 15 min

JIS:

Japan Integrated Staging

Moderate:

moderately differentiated hepatocellular carcinoma

NAFLD:

nonalcoholic fatty liver disease

NED:

no evidence of disease

non-B non-C:

neither hepatitis B virus surface antigen nor hepatitis C virus antibody

Poor:

poorly differentiated hepatocellular carcinoma

PS:

prediction score

RR:

relative risk

Well:

well differentiated hepatocellular carcinoma.

References

  1. Miyagawa S, Kawasaki S, Makuuchi M. Comparison of the characteristics of hepatocellular carcinoma between hepatitis B and C viral infection: tumor multicentricity in cirrhotic liver with hepatitis C. Hepatology 1996;24: 307–310

    Article  PubMed  CAS  Google Scholar 

  2. Kiyosawa K, Sodeyama T, Tanaka E, et al. Interrelationship of blood transfusion, non-A, non-B hepatitis and hepatocellular carcinoma: analysis by detection of antibody to hepatitis C virus. Hepatology 1990;12: 671–675

    Article  PubMed  CAS  Google Scholar 

  3. Kubo S, Nishiguchi S, Hirohashi K, et al. High prevalence of infection with hepatitis B and C viruses in patients with hepatocellular carcinoma in Japan. Hepatogastroenterology 1999;46: 357–359

    PubMed  CAS  Google Scholar 

  4. Shiratori Y. Different clinicopathological features of hepatitis B- and C-related hepatocellular carcinoma. J Gastroenterol Hepatol 1996;11: 942–943

    PubMed  CAS  Google Scholar 

  5. Brechot C, Poucel C, Louise A, Rain B, Tiollaris P. Presence of integrated hepatitis B virus DNA sequences in cellular DNA of human hepatocellular carcinoma. Nature 1980;286: 533–535

    Article  PubMed  CAS  Google Scholar 

  6. Bressac B, Galvin KM, Liang TJ, Isselbacher KJ, Wands JR, Ozturk M. Abnormal structure and expression of p53 gene in human hepatocellular carcinoma. Proc Natl Acad Sci USA 1990;87: 1973–1977

    Article  PubMed  CAS  Google Scholar 

  7. Sherlock S. Viruses and hepatocellular carcinoma. Gut 1994;35: 828–832

    PubMed  CAS  Google Scholar 

  8. Tarao K, Ohkawa S, Shimizu A, et al. Significance of hepatocellular proliferation in the development of hepatocellular carcinoma from anti-hepatitis C virus-positive cirrhotic patients. Cancer 1994;73: 1149–1154

    Article  PubMed  CAS  Google Scholar 

  9. Aihara T, Noguchi S, Sasaki Y, Nakano H, Imaoka S. Clonal analysis of regenerative nodules in hepatitis C virus-induced liver cirrhosis. Gastroenterology 1994;107: 1805–1811

    PubMed  CAS  Google Scholar 

  10. Moriya K, Fujie H, Shintani Y, et al. The core protein of hepatitis C virus induces hepatocellular carcinoma in transgenic mice. Nat Med 1998;4: 1065–1067

    Article  PubMed  CAS  Google Scholar 

  11. Shiratori Y, Shiina S, Imamura M, et al. Characteristic difference of hepatocellular carcinoma between hepatitis B- and C- viral infection in Japan. Hepatology 1995;22: 1027–1033

    PubMed  CAS  Google Scholar 

  12. Ikeda K, Saitoh S, Koida I, et al. A multivariate analysis of risk factors for hepatocellular carcinogenesis: a prospective observation of 795 patients with viral and alcoholic cirrhosis. Hepatology 1993;18: 47–53

    PubMed  CAS  Google Scholar 

  13. Yu MC, Tong MJ, Govindarajan S, Henderson BE. Nonviral risk factors for hepatocellular carcinoma in a low-risk population, the non-Asians of Los Angeles County, California. J Natl Cancer Inst 1991;83: 1820–1826

    Article  PubMed  CAS  Google Scholar 

  14. Yamanaka N, Tanaka T, Tanaka W, et al. Correlation of hepatitis virus serologic status with clinicopathologic features in patients undergoing hepatectomy for hepatocellular carcinoma. Cancer 1997;79: 1509–1515

    Article  PubMed  CAS  Google Scholar 

  15. Nagasue N, Ono T, Yamanoi A, Kohno H, El-Assal ON, Taniura H, Uchida M. Prognostic factors and survival after hepatic resection for hepatocellular carcinoma without cirrhosis. Br J Surg 2001;88: 515–522

    Article  PubMed  CAS  Google Scholar 

  16. Roayaie S, Haim MB, Emre S, et al. Comparison of surgical outcomes for hepatocellular carcinoma in patients with hepatitis B versus hepatitis C: a western experience. Ann Surg Oncol 2000;7: 764–770

    Article  PubMed  CAS  Google Scholar 

  17. Dohmen K, Shigematsu H, Irie K, Ishibashi H. Comparison of the clinical characteristics among hepatocellular carcinoma of hepatitis B, hepatitis C and non-B non-C patients. Hepatogastroenterology 2003;50: 2022–2027

    PubMed  Google Scholar 

  18. Chen MF, Jeng LB, Lee WC, Chen TC. Surgical results in patients with dual hepatitis B- and C-related hepatocellular carcinoma compared with hepatitis B- or C-related hepatocellular carcinoma. Surgery 1998;123: 554–559

    Article  PubMed  CAS  Google Scholar 

  19. Takeda S, Nagafuchi Y, Tashiro H, et al. Antihepatitis C virus status in hepatocellular carcinoma and the influence on clinicopathological findings and operative results. Br J Surg 1992;79: 1195–1198

    Article  PubMed  CAS  Google Scholar 

  20. Yamanaka N, Okamoto E, Oriyama T, et al. A prediction scoring system to select the surgical treatment of liver cancer. Further refinement based on 10 years of use. Ann Surg 1994;219: 342–346

    Article  PubMed  CAS  Google Scholar 

  21. The Brisbane 2000 Terminology of Liver Anatomy and Resection. Terminology Committee of the International Hepato-Pancreato-Biliary Association. HPB 2000;2: 333–339

    Google Scholar 

  22. The Cancer of the Liver Italian Program (CLIP) Investigators. A new prognostic system for hepatocellular carcinoma: A retrospective study of 435 patients. Hepatology 1998;28: 751–755

    Article  Google Scholar 

  23. Kudo M, Chung H, Osaki Y. Prognostic staging system for hepatocellular carcinoma (CLIP score): Its value and limitations, and a proposal for a new staging system, the Japan Integrated Staging Score (JIS score). J Gastroenterol 2003;38: 207–215

    Article  PubMed  Google Scholar 

  24. Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 1973;60: 646–649

    Article  PubMed  CAS  Google Scholar 

  25. Greene FL, Page DL, Fleming ID, et al. AJCC cancer staging manual. 6th ed. Chicago, USA: Springer; 2002. p. 131–144

    Google Scholar 

  26. Ichida F, Tsuji T, Omata M, et al. New Inuyama classification for histological assessment of chronic hepatitis. Int Hepatol Commun 1996;6: 112–119

    Article  Google Scholar 

  27. Takano S, Yokosuka O, Imazeki F, Tagawa M, Omata M. Incidence of hepatocellular carcinoma in chronic hepatitis B, C: a prospective study of 251 patients. Hepatology 1995;21: 650–655

    PubMed  CAS  Google Scholar 

  28. Shiratori Y, Shiina S, Zhang PY, et al. Does dual infection by hepatitis B and C viruses play an important role in the pathogenesis of hepatocellular carcinoma in Japan? Cancer 1997;80: 2060–2067

    Article  PubMed  CAS  Google Scholar 

  29. Wakai T, Shirai Y, Yokoyama N, Nagakura S, Hatakeyama K. Hepatitis viral status affects the pattern of intrahepatic recurrence after resection for hepatocellular carcinoma. Eur J Surg Oncol 2003;29: 266–271

    Article  PubMed  CAS  Google Scholar 

  30. 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  PubMed  CAS  Google Scholar 

  31. Takenaka K, Adachi E, Nishizaki T, Hiroshige K, Ikeda T, Tsuneyoshi M, Sugimachi K. Possible multicentric occurrence of hepatocellular carcinoma: a clinicopathological study. Hepatology 1994;19: 889–894

    Article  PubMed  CAS  Google Scholar 

  32. Shimada M, Hamatsu T, Yamashita Y, et al. Characteristics of multicentric hepatocellular carcinomas: comparison with intrahepatic metastasis. World J Surg 2001;25: 991–995

    Article  PubMed  CAS  Google Scholar 

  33. Nakano S, Haratake J, Okamoto K, Takeda S. Investigation of resected multinodular hepatocellular carcinoma: assessment of unicentric or multicentric genesis from histological and prognostic viewpoint. Am J Gastroenterol 1994;89: 189–193

    PubMed  CAS  Google Scholar 

  34. Koike Y, Shiratori Y, Sato S, 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: 1216–1223

    Article  PubMed  CAS  Google Scholar 

  35. Portolani N, Coniglio A, Ghidoni S, Giovanelli M, Benetti A, Tiberio GA, Giulini SM. Early and late recurrence after liver resection for hepatocellular carcinoma: prognostic and therapeutic implications. Ann Surg 2006;243: 229–235

    Article  PubMed  Google Scholar 

  36. Ikeda K, Saitoh S, Tsubota A, et al. Risk factors for tumor recurrence and prognosis after curative resection of hepatocellular carcinoma. Cancer 1993;71: 19–25

    Article  PubMed  CAS  Google Scholar 

  37. Belghiti J, Panis Y, Farges O, Benhamou JP, Fekete F. Intrahepatic recurrence after resection of hepatocellular carcinoma complicating cirrhosis. Ann Surg 1991;214: 114–117

    Article  PubMed  CAS  Google Scholar 

  38. Pompili M, Rapaccini GL, de Luca F, et al. Risk factors for intrahepatic recurrence of hepatocellular carcinoma in cirrhotic patients treated by percutaneous ethanol injection. Cancer 1997;79: 1501–1508

    Article  PubMed  CAS  Google Scholar 

  39. Lise M, Bacchetti S, Da Pian P, Nitti D, Pilati PL, Pigato P. Prognostic factors affecting long-term outcome after liver resection for hepatocellular carcinoma: results in a series of 100 Italian patients. Cancer 1998;82: 1028–1036

    Article  PubMed  CAS  Google Scholar 

  40. Yamamoto J, Kosuge T, Takayama T, et al. Perioperative blood transfusion promotes recurrence of hepatocellular carcinoma after hepatectomy. Surgery 1994;115: 303–309

    PubMed  CAS  Google Scholar 

  41. 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: 661–665

    PubMed  CAS  Google Scholar 

  42. Kuhns M, McNamara A, Mason A, Campbell C, Perrillo R. Serum and liver hepatitis B virus DNA in chronic hepatitis B after sustained loss of surface antigen. Gastroenterology 1992;103: 1649–56

    PubMed  CAS  Google Scholar 

  43. Fong TL, Di Bisceglie AM, Gerber MA, Waggoner JG, Hoofnagle JH. Persistence of hepatitis B virus DNA in the liver after loss of HBsAg in chronic hepatitis B. Hepatology 1993;18: 1313–8

    PubMed  CAS  Google Scholar 

  44. Fattovich G, Stroffolini T, Zagni I, Donato F. Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology 2004;127: S35–S50

    Article  PubMed  Google Scholar 

  45. Marrero JA, Fontana RJ, Su GL, Conjeevaram HS, Emick DM, Lok AS. NAFLD may be a common underlying liver disease in patients with hepatocellular carcinoma in the United States. Hepatology 2002;36: 1349–1354

    Article  PubMed  Google Scholar 

  46. Clark JM. The epidemiology of nonalcoholic fatty liver disease in adults. J Clin Gastroenterol 2006;40: S5–S10

    PubMed  Google Scholar 

  47. Reid AE. Nonalcoholic steatohepatitis. Gastroenterology 2001;121: 710–723

    Article  PubMed  CAS  Google Scholar 

  48. Paterlini P, Gerken G, Nakajima E, et al. Polymerase chain reaction to detect hepatitis B virus DNA and RNA sequences in primary liver cancers from patients negative for hepatitis B surface antigen. N Engl J Med 1990;323: 80–85

    Article  PubMed  CAS  Google Scholar 

  49. Allain JP. Occult hepatitis B virus infection. Transfus Clin Biol 2004;11: 18–25

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan

    Hiroshi Shimada MD, PhD, Kenichi Matsuo MD, Yasuhiko Nagano MD, Itaru Endo MD, PhD & Shinji Togo MD, PhD

  2. Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan

    Kuniya Tanaka MD, PhD

Authors
  1. Kuniya Tanaka MD, PhD
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  2. Hiroshi Shimada MD, PhD
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  3. Kenichi Matsuo MD
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  4. Yasuhiko Nagano MD
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  5. Itaru Endo MD, PhD
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  6. Shinji Togo MD, PhD
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Correspondence to Kuniya Tanaka MD, PhD.

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Tanaka, K., Shimada, H., Matsuo, K. et al. Clinical Characteristics and Surgical Outcome in Hepatocellular Carcinoma without Hepatitis B Virus Surface Antigen or Hepatitis C Virus Antibody. Ann Surg Oncol 14, 1170–1181 (2007). https://doi.org/10.1245/s10434-006-9299-y

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  • DOI: https://doi.org/10.1245/s10434-006-9299-y

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