Journal of Gastroenterology

, 44:1190 | Cite as

Hepatocellular carcinoma arising from non-cirrhotic nonalcoholic steatohepatitis

  • Natsuko Kawada
  • Kazuho Imanaka
  • Tsukasa Kawaguchi
  • Chie Tamai
  • Ryu Ishihara
  • Takashi Matsunaga
  • Kunihito Gotoh
  • Terumasa Yamada
  • Yasuhiko Tomita
Original Article—Liver, Pancreas, and Biliary Tract

Abstract

Purpose

Characteristics of hepatocellular carcinoma (HCC) complicating nonalcoholic steatohepatitis (NASH) are still controversial. Most NASH related HCCs are believed to develop from cirrhotic liver, but case reports about HCC arising from non-cirrhotic NASH have been accumulating recently. This study is designed to elucidate characteristics of NASH related HCC diagnosed with high accuracy by using surgically resected specimens that contain larger areas to validate than biopsy specimens.

Methods

For this study, 1168 patients who underwent hepatic resection at Osaka Medical Center for Cancer and Cardiovascular Diseases were enrolled. Patients who had clinically obvious causes of chronic liver dysfunction, such as viral and alcoholic hepatitis, were excluded. Histological diagnosis of NASH was confirmed according to Brunt’s criterion.

Results

Eight (1%) patients were diagnosed with NASH. Six (75%) of them showed non-cirrhosis in non-cancerous areas. Stages of fibrosis in the non-cirrhotic patients were mild fibrosis (F2) in five and moderate fibrosis (F3) in one. All patients complicated with metabolic diseases. Although all these patients without cirrhosis were evaluated pathologically at tumor-node-metastasis stages I or II, three (50%) had multiple recurrences of tumor within a short time after surgery.

Conclusion

This study indicates HCC might arise frequently from non-cirrhotic NASH. While further studies are needed to confirm this observation, both cirrhotic and non-cirrhotic NASH warrant regular screening for HCC.

Keywords

Non-alcoholic steatohepatitis Hepatocellular carcinoma Cirrhosis 

References

  1. 1.
    Ludwig J, Viggiano TR, McGill DB, Oh BJ. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc. 1980;55:434–8.PubMedGoogle Scholar
  2. 2.
    Powell EE, Cooksley WG, Hanson R, Searle J, Halliday JW, Powell LW. The natural history of nonalcoholic steatohepatitis: a follow-up study of forty-two patients for up to 21 years. Hepatology. 1990;11:74–80.CrossRefPubMedGoogle Scholar
  3. 3.
    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;38:420–7.CrossRefPubMedGoogle Scholar
  4. 4.
    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;33:72–6.CrossRefPubMedGoogle Scholar
  5. 5.
    Hashizume H, Sato K, Takagi H, Hirokawa T, Kojima A, Sohara N, et al. Primary liver cancers with nonalcoholic steatohepatitis. Eur J Gatroenterol Hepatol. 2007;19:827–34.CrossRefGoogle Scholar
  6. 6.
    Shimada M, Hashimoto E, Taniai M, Hasegawa K, Okuda H, Hayashi N, et al. Hepatocellular carcinoma in patients with non-alcoholic steatohepatitis. J Hepatol. 2002;37:154–60.CrossRefPubMedGoogle Scholar
  7. 7.
    Bugianesi E, Leone N, Vanni E, Marchesini G, Brunello F, Carucci P, et al. Expanding the natural history of nonalcoholic steatohepatitis from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology. 2002;123:134–40.CrossRefPubMedGoogle Scholar
  8. 8.
    Guzman G, Brunt EM, Petrovic M, Chejfec G, Layden TJ, Cotler SJ. Does nonalcoholic fatty liver disease predispose patients to hepatocellular carcinoma in the absence of cirrhosis? Arch Pathol Lab Med. 2008;132:1761–6.PubMedGoogle Scholar
  9. 9.
    Ichikawa T, Yanagi K, Motoyoshi Y, Hamasaki K, Nakao K, Toriyama K, et al. Two cases of non-alcoholic steatohepatitis with development of hepatocellular carcinoma without cirrhosis. J Gastroenterol Hepatol. 2006;21:1865–6.CrossRefPubMedGoogle Scholar
  10. 10.
    Bullock RE, Zaitoun AM, Aithal GP, Ryder SD, Beckingham IB, Lobo DN. Association of non-alcoholic steatohepatitis without significant fibrosis with hepatocellular carcinoma. J Hepatol. 2004;41:685–90.CrossRefPubMedGoogle Scholar
  11. 11.
    Manning DS, Afdhal NN. Diagnosis and quantitation of fibrosis. Gastroenterology. 2008;134:1670–81.CrossRefPubMedGoogle Scholar
  12. 12.
    Ratziu V, Charlotte F, Heurtier A, Gombert S, Giral P, Bruckert E, et al. Sampling variability of liver biopsy in nonalcoholic fatty liver disease. Gastroenterology. 2005;128:1898–906.CrossRefPubMedGoogle Scholar
  13. 13.
    Regev A, Berho M, Jeffers LJ, Milikowski C, Molina EG, Pyrsopoulos NT, et al. Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV infection. Am J Gatstroenterol. 2002;97:2614–8.CrossRefGoogle Scholar
  14. 14.
    Brunt EM, Janney CG, Di Biscegli AM, Neuschwander-Tetri BA, Bacon BR. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol. 1999;94:2467–74.CrossRefPubMedGoogle Scholar
  15. 15.
    Liver Cancer Study Group of Japan. The general rules for the clinical and pathological study of primary liver cancer (in Japanese). 5th ed. Tokyo: Kanehara Press; 2007.Google Scholar
  16. 16.
    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.CrossRefPubMedGoogle Scholar
  17. 17.
    Kumada T, Nakano S, Takeda I, Sugiyama K, Osada T, Kiriyama S, et al. Patterns of recurrence after initial treatment in patients with small hepatocellular carcinoma. Hepatology. 1997;25:87–92.CrossRefPubMedGoogle Scholar

Copyright information

© Springer 2009

Authors and Affiliations

  • Natsuko Kawada
    • 1
  • Kazuho Imanaka
    • 1
  • Tsukasa Kawaguchi
    • 1
  • Chie Tamai
    • 1
  • Ryu Ishihara
    • 1
  • Takashi Matsunaga
    • 2
  • Kunihito Gotoh
    • 3
  • Terumasa Yamada
    • 3
  • Yasuhiko Tomita
    • 4
  1. 1.Department of Gastrointestinal OncologyOsaka Medical Center for Cancer and Cardiovascular DiseasesOsakaJapan
  2. 2.Department of Medical InformaticsOsaka Medical Center for Cancer and Cardiovascular DiseasesOsakaJapan
  3. 3.Department of SurgeryOsaka Medical Center for Cancer and Cardiovascular DiseasesOsakaJapan
  4. 4.Department of PathologyOsaka Medical Center for Cancer and Cardiovascular DiseasesOsakaJapan

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