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Prospective study of hepatocellular carcinoma in nonalcoholic steatohepatitis in comparison with hepatocellular carcinoma caused by chronic hepatitis C

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

Background

This study was performed to clarify the outcomes and recurrence of hepatocellular carcinoma (HCC) in nonalcoholic steatohepatitis (NASH) in comparison with the data for HCC caused by hepatitis C virus (HCV) infection.

Methods

Data for 34 NASH patients with HCC (NASH-HCC) were analyzed prospectively, and data for 56 age- and sex-matched patients with HCC due to HCV chronic liver disease (HCV-HCC) were collected retrospectively. After the initial treatment for HCC, patients were followed regularly at least every 4 months by performing clinical examinations, serum liver function tests, monitoring alpha-fetoprotein and des-gamma-carboxy prothrombin, and utilizing various imaging modalities.

Results

The five-year survival rate was 55.2% and the cumulative recurrence of HCC at 5 years was 69.8% in treated cases of NASH-HCC. The NASH-HCC and HCV-HCC groups showed similar survival and recurrence rates. Of the 16 NASH-HCC patients curatively treated, recurrence was detected more than 2 years after the initial treatment in 9. Three patients showed intrahepatic recurrences away from the initial HCC, and 3 patients showed a change in tumor marker production after treatment of the initial HCC. The size of the HCC and the stage of fibrosis were significant risk factors for HCC recurrence in NASH-HCC.

Conclusions

HCC recurrence was very high in NASH, and the HCC may be of multicentric origin, similar to HCC based on viral hepatitis. Regular screening for HCC is extremely important for NASH patients with HCC, even after curative treatment. This study confirmed that NASH-HCC has a similar course to that of HCV-HCC.

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Abbreviations

HCC:

Hepatocellular carcinoma

NASH:

Nonalcoholic steatohepatitis

HCV:

Hepatitis C virus

NASH-HCC:

NASH patients with HCC

HCV-HCC:

HCC due to HCV chronic liver disease

References

  1. El-Serag HM, Lenhard RK. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132:2557–76.

    Article  CAS  PubMed  Google Scholar 

  2. Health and Welfare Statistics. Health and Welfare Statistics Association. The analysis of health in Japan. J Health Welf Stat. 2004;51:35–76.

    Google Scholar 

  3. Kudo M, Arii S, Ikari I, Okazaki M, Okita K, Omata M, et al. The nationwide report registered every 2 years by the Liver Cancer Study Group of Japan (in Japanese with English abstract). Kanzo 2007;48:117–140.

    Google Scholar 

  4. Shimada M, Hashimoto E, Taniai M, Hasegawa K, Okuda H, Hayashi N. Hepatocellular carcinoma in patients with non-alcoholic steatohepatitis. J Hepatol. 2002;37:154–60.

    Article  PubMed  Google Scholar 

  5. Hashimoto E, Yatsuji S, Tobari M, Taniai M, Torii N, Tokushige K, et al. Hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. J Gastroenterol. 2009;44:89–95.

    Article  PubMed  Google Scholar 

  6. Yatsuji S, Hashimoto E, Tobari M, Taniai M, Tokushige K, Shiratori K. Clinical features and outcomes of cirrhosis due to non-alcoholic steatohepatitis compared with cirrhosis caused by chronic hepatitis C. J Gastroenterol Hepatol. 2009;24:248–54.

    Article  CAS  PubMed  Google Scholar 

  7. Ekstedt M, Franzen LE, Mathiensen UL, Thorelius L, Holmqvist M, Bodemar G, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology. 2006;44:802–5.

    Article  Google Scholar 

  8. Sanyal AJ, Banas C, Sargeant C, Luketic VA, Sterling RK, Stravitz RT, et al. Similarities and differences in outcomes of cirrhosis due to nonalcoholic steatohepatitis and hepatitis C. Hepatology. 2006;43:682–9.

    Article  PubMed  Google Scholar 

  9. Ratziu V, Bonyhay L, Di Martino V, Charlotte F, Cavallaro L, Sayegh-Tainturier MH, et al. Survival, liver failure, and hepatocellular carcinoma in obesity-related cryptogenic cirrhosis. Hepatology. 2002;35:1485–93.

    Article  PubMed  Google Scholar 

  10. Sanyal AJ, American Gastroenterological Association. AGA technical review on nonalcoholic fatty liver disease. Gastroenterology. 2002;123:1705–25.

    Article  PubMed  Google Scholar 

  11. American Gastroenterological Association. American Gastroenterological Association medical position statement: nonalcoholic fatty liver disease. Gastroenterology. 2002;123:1702–4.

    Article  Google Scholar 

  12. Neuschwander-Tetri BA, Caldwell SH. Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. Hepatology. 2003;37:1202–19.

    Article  PubMed  Google Scholar 

  13. Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41:1313–21.

    Article  PubMed  Google Scholar 

  14. Brunt EM, Janney CG, Di Bisceglie AM, Neuschwander-Tetri BA, Bacon BR. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol. 1999;94:2467–74.

    Article  CAS  PubMed  Google Scholar 

  15. Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R, Burroughs AK. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona 2000 EASL Conference. European Association for the Study of the Liver. J Hepatol. 2001;35:421–30.

    Google Scholar 

  16. Minagawa M, Ikai I, Matsuyama Y, Yamaoka Y, Makuuchi M. Staging of hepatocellular carcinoma assessment of the Japanese TNM and AJCC/UICC TNM systems in a cohort of 13,772 patients in Japan. Ann Surg. 2007;245:909–22.

    Google Scholar 

  17. Edmondson HA, Steiner PE. Primary carcinoma of the liver. A study of 100 cases among 4900 necropsies. Cancer. 1954;7:462–503.

    Article  CAS  PubMed  Google Scholar 

  18. Zen Y, Katayanagi K, Tsuneyama K, Harada K, Araki I, Nakanuma Y. Hepatocellular carcinoma arising in non-alcoholic steatohepatitis. Pathol Int. 2001;51:127–31.

    Article  CAS  PubMed  Google Scholar 

  19. Imamura H, Matsuyama Y, Tanaka E, Ohkubo T, Hasegawa K, Miyagawa S, et al. Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy. J Hepatol. 2003;38:200–7.

    Article  PubMed  Google Scholar 

  20. Koda M, Murawaki Y, Mitsuda A, Ohyama K, Horie Y, Suou T, et al. Predictive factors for intrahepatic recurrence after percutaneous ethanol injection therapy for small hepatocellular carcinoma. Cancer. 2000;88:529–37.

    Article  CAS  PubMed  Google Scholar 

  21. 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 

  22. Toyoda H, Kumada T, Kiriyama S, Sone Y, Tanikawa M, Hisanaga Y, et al. Characteristics and prognosis of patients in Japan with viral marker-negative hepatocellular carcinoma. J Gastroenterol Hepatol. 2008;23:459–66.

    Article  PubMed  Google Scholar 

  23. Taura K, Ikai I, Hatano E, Fujii H, Uyama N, Shimahara Y. Implication of frequent local ablation therapy for intrahepatic recurrence in prolonged survival of patients with hepatocellular carcinoma undergoing hepatic resection. Ann Surg. 2006;244:265–73.

    Article  PubMed  Google Scholar 

  24. Sassa T, Kumada T, Nakano S, Uematsu T. Clinical utility of simultaneous measurement of serum high-sensitivity des-gamma-carboxy prothrombin and Lens culinaris agglutinin A-reactive alpha-fetoprotein in patients with small hepatocellular carcinoma. J Gastroenterol Hepatol. 1999;11:1387–92.

    Article  CAS  Google Scholar 

  25. Okuda H, Nakanishi T, Takatsu K, Saito A, Hayashi N, Takasaki K, et al. Serum levels of des-gamma-carboxy prothrombin measured using the revised enzyme immunoassay kit with increased sensitivity in relation to clinicopathologic features of solitary hepatocellular carcinoma. Cancer. 2000;88:544–9.

    Article  CAS  PubMed  Google Scholar 

  26. Caldwell S, Park SH. The epidemiology of hepatocellular cancer: from the perspectives of public health problem to tumor biology. J Gastroenterol. 2009;44(Suppl 19):96–101.

    Article  PubMed  Google Scholar 

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Acknowledgments

This work was supported in part by a grant-in-aid (200831026A) from the Ministry of Health, Labor and Welfare, Japan.

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Authors and Affiliations

  1. Department of Internal Medicine and Gastroenterology, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan

    Katsutoshi Tokushige, Etsuko Hashimoto, Satoru Yatsuji, Maki Tobari, Makiko Taniai, Nobuyuki Torii & Keiko Shiratori

Authors
  1. Katsutoshi Tokushige
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  2. Etsuko Hashimoto
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  3. Satoru Yatsuji
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  4. Maki Tobari
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  5. Makiko Taniai
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  6. Nobuyuki Torii
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  7. Keiko Shiratori
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Correspondence to Etsuko Hashimoto.

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Tokushige, K., Hashimoto, E., Yatsuji, S. et al. Prospective study of hepatocellular carcinoma in nonalcoholic steatohepatitis in comparison with hepatocellular carcinoma caused by chronic hepatitis C. J Gastroenterol 45, 960–967 (2010). https://doi.org/10.1007/s00535-010-0237-1

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  • DOI: https://doi.org/10.1007/s00535-010-0237-1

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