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Hepatocellular carcinoma in patients with nonalcoholic steatohepatitis

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Abstract

Background

There have been few reports on hepatocellular carcinoma (HCC) in nonalcoholic steatohepatitis (NASH) and the natural history of NASH. Accordingly, we assessed the clinical features of HCC in NASH, the risk factors for HCC, and natural history of NASH with advanced fibrosis.

Patients and methods

There were 34 NASH patients with HCC and 348 NASH patients without HCC. To clarify the clinical features of NASH patients with HCC and to determine the risk factors for HCC, we compared NASH patients with HCC with those without HCC. Univariate and multivariate logistic regression models were used for statistical analysis. A prospective cohort study of the outcomes of 137 NASH with advanced fibrosis was started in 1990. The impact of baseline risk factors on the development of HCC and survival was evaluated by Cox regression analysis.

Results

In total, 88% of patients with HCC had advanced fibrosis, with a median age of 70 years. Older age, low level of AST, low grade of histological activity, and advanced stage of fibrosis were risk factors for HCC. A prospective cohort study showed that the 5-year cumulative incidence of HCC was 7.6%, and the 5-year survival rate was 82.8%. HCC was the leading cause of death.

Conclusions

The present study confirmed that older age and advanced fibrosis were important risk factors for HCC, and that HCC was the major cause of mortality in NASH patients with advanced fibrosis. Regular screening for HCC is thus extremely important for NASH patients with advanced fibrosis.

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References

  1. Amarapurkar DN, Hashimoto E, Lesmana LA, Sollano JD, Chen PJ, Goh KL, et al. How common is non-alcoholic fatty liver disease in the Asia-Pacific region and are there local differences? J Gastroenterol Hepatol 2007;22:788–793.

    Article  PubMed  Google Scholar 

  2. Chitturi S, Farrell GC, Hashimoto E, Saibara T, Lau GK, Sollano JD, et al. Non-alcoholic fatty disease in Asia-Pacific region: definitions and overview of proposed guidelines. J Gastroenterol Hepatol 2007;22:778–787.

    Article  PubMed  Google Scholar 

  3. Jimba S, Nakagami T, Takahashi M, Wakamatsu T, Hirota Y, Iwamoto Y, et al. Prevalence of non-alcoholic fatty liver disease and its association with impaired glucose metabolism in Japanese adults. Diabet Med 2005;22:1141–1145.

    Article  PubMed  CAS  Google Scholar 

  4. Kojima S, Watanabe N, Numata M, Ogawa T, Matsuzaki S. Increase in the prevalence of fatty liver in Japan over the past 12 years: analysis of clinical background. J Gastroenterol 2003;38:954–961.

    Article  PubMed  Google Scholar 

  5. Liou I, Kowdley KV. Natural history of nonalcoholic steatohepatitis. J Clin Gastrotenterol 2006;40(suppl 1):S11–S16.

    Google Scholar 

  6. Bugianesi E. Non-alcoholic steatohepatitis and cancer. Clin Liver Dis 2007;11:191–207.

    Article  PubMed  CAS  Google Scholar 

  7. De Alwis N, Day CP. Non-alcoholic fatty liver disease: The mist gradually clears. J Hepatol 2008;48:S104–S112.

    PubMed  Google Scholar 

  8. Shimada M, Hashimoto E, Taniai M, Hasegawa K, Okuda H, Hayashi N. Hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. J Hepatol 2002;37:154–160.

    Article  PubMed  Google Scholar 

  9. Yoshioka Y, Hashimoto E, Yatsuji S, Kaneda H, Taniai M, Tokushige K, et al. Nonalcoholic steatohepatitis: cirrhosis, hepatocellular carcinoma, and burnt-out NASH. J Gastroenterol 2004;39:1215–1218.

    Article  PubMed  Google Scholar 

  10. Atsumi Y, Yatsuji S, Torii N, Tokushige K, Hashimoto E, Yamamoto M, et al. Hepatocellular carcinoma arising in nonalcoholic steatohepatitis (NASH) without advanced fibrosis (in Japanese with English abstract). Kanzo 2007;48:604–609.

    Article  Google Scholar 

  11. Hashimoto E, Taniai M, Kaneda H, Tokushige K, Hasegawa K, Okuda H, et al. Comparison of hepatocellular carcinoma patients with alcoholic liver disease and nonalcoholic steatohepatitis. Alcohol Clin Exp Res 2004;28:164S–168S.

    PubMed  Google Scholar 

  12. Hashimoto E, Yatsuji S, Kaneda H, Yoshioka Y, Taniai M, Tokushige K, et al. The characteristics and natural history of Japanese patients with nonalcoholic fatty liver disease. Hepatol Res 2005;33:72–76.

    Article  PubMed  Google Scholar 

  13. Hui JM, Kench JG, Chitturi S, Sud A, Farrell GC, Byth K, et al. Long-term outcomes of cirrhosis in nonalcoholic steatohepatitis compared with hepatitis C. Hepatology 2003;38:420–427.

    Article  PubMed  Google Scholar 

  14. 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;43:682–689.

    Article  PubMed  Google Scholar 

  15. 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;35:1485–1493.

    Article  PubMed  Google Scholar 

  16. 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;44:802–805.

    Article  Google Scholar 

  17. Sanyal AJ. American Gastroenterological Association. AGA technical review on nonalcoholic fatty liver disease. Gastroenterology 2002;123:1705–1725.

    Article  PubMed  Google Scholar 

  18. American Gastroenterological Association. American Gastroenterological Association medical position statement: nonalcoholic fatty liver disease. Gastroenterology 2002;123:1702–1704.

    Article  Google Scholar 

  19. Neuschwander-Tetri BA, Caldwell SH. Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. Hepatology 2003;37:1202–1219.

    Article  PubMed  Google Scholar 

  20. 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;41:1313–1321.

    Article  PubMed  Google Scholar 

  21. 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;94:2467–2474.

    Article  PubMed  CAS  Google Scholar 

  22. Brunt EM. Nonalcoholic steatohepatitis. Semin Liver Dis 2004;24:3–20.

    PubMed  Google Scholar 

  23. 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;35:421–430

    Article  PubMed  CAS  Google Scholar 

  24. El-Serag HM, Lenhard RK. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 2007;132:2557–2576.

    Article  PubMed  CAS  Google Scholar 

  25. Journal of Health and Welfare Statistics. Health and Welfare Statistics Association Japan; 2004.

  26. 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 

  27. 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;348:1625–1638.

    Article  PubMed  Google Scholar 

  28. Caldwell SH, Crespo DM, Kang HS, Al-Osaimi AM. Obesity and hepatocellular carcinoma. Gastroenterology 2004;127(suppl 1):S97–S103.

    Article  PubMed  CAS  Google Scholar 

  29. Ohki T, Tateishi R, Sato T, Masuzaki R, Imamura J, Goto T, et al. Obesity in an independent risk factor for hepatocellular carcinoma development in chronic hepatitis C patients. Clin Gastroenterol Hepatol 2008;6:459–464.

    Article  PubMed  Google Scholar 

  30. Inoue M, Iwasaki M, Otani T, Sasazuk S, Noda M, Tusgane S, et al. Diabetes mellitus and the risk of cancer. Result from a largescale population-based cohort study in Japan. Arch Intern Med 2006;166:1871–1877.

    Article  PubMed  Google Scholar 

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Hashimoto, E., Yatsuji, S., Tobari, M. et al. Hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. J Gastroenterol 44 (Suppl 19), 89–95 (2009). https://doi.org/10.1007/s00535-008-2262-x

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  • DOI: https://doi.org/10.1007/s00535-008-2262-x

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