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Hepatocellular carcinoma in Japanese patients with nonalcoholic fatty liver disease and alcoholic liver disease: multicenter survey

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background

In Japan, the prevalence of hepatocellular carcinoma (HCC) associated with nonviral liver disease, especially with nonalcoholic fatty liver disease (NAFLD-HCC) and alcoholic liver disease (ALD-HCC), has been increasing. Clarification of the clinical features of NAFLD-HCC and ALD-HCC is needed. We performed a large retrospective multicenter survey to clarify the clinical course of these two types of HCC.

Methods

Clinical characteristics, survival, and recurrence were examined in 532 patients with ALD-HCC and 209 patients with NAFLD-HCC who were diagnosed between January 2000 and December 2013.

Results

The ALD-HCC patients were predominantly male and were younger than the patients with NAFLD-HCC. Lifestyle-related diseases were significantly more common in the NAFLD-HCC group, but the prevalence of cirrhosis was significantly higher in the ALD-HCC group. The histological diagnosis of NAFLD-HCC showed a gender difference (F4; 72.7 % in the females vs. 37.6 % in the males). The characteristic features of HCC including histology, survival rate, and recurrence rate were quite similar in the NAFLD-HCC and ALD-HCC groups: 5-year survival rates 49.1 vs. 43.7 %; 5-year recurrence rates 69.6 vs. 65.4 %, respectively. However, the risk factors for recurrence differed between the two groups: des-gamma-carboxy prothrombin was a risk factor in NAFLD-HCC and α-fetoprotein was a risk factor in ALD-HCC.

Conclusions

Although the characteristic features underlying these two diseases are different, the two HCC groups showed a similar clinical course. The recurrence rates of the two HCC groups were relatively high. We found that critical tumor markers for recurrence differed between the two diseases.

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Abbreviations

ALD:

Alcoholic liver disease

ALD-HCC:

HCC associated with alcoholic liver disease

f-IRI:

Fasting immunoreactive insulin

HBV:

Hepatitis B virus

HCC:

Hepatocellular carcinoma

HCV:

Hepatitis C virus

NAFLD:

Nonalcoholic fatty liver disease

NAFLD-HCC:

HCC associated with nonalcoholic fatty liver disease

DCP:

Des-gamma-carboxy prothrombin

AFP:

α-fetoprotein

References

  1. GLOBOCAN2012: Estimated cancer incidence, mortality and prevalence worldwide 2012. http://globocan.iarc.fr/.

  2. Journal of Health and Welfare Statistics. Health and Welfare Statistics Association 2013 Japan. 60, 51–75.

  3. Ikai I, Arii S, Okazaki M, Okita K, et al. Report of the 17th nationwide follow-up survey of primary liver cancer in Japan. Hepatol Res. 2010;40:1043–59.

    Article  Google Scholar 

  4. Tokushige K, Hashimoto E, Horie Y, et al. Hepatocellular carcinoma in Japanese patients with nonalcoholic fatty liver disease, alcoholic liver disease and chronic liver disease of unknown etiology: report of the nationwide survey. J Gastroenterol. 2011;46:1230–7.

    Article  PubMed  Google Scholar 

  5. Tateishi R, Okanoue T, Fujiwara N, et al. Clinical characteristics, treatment, and prognosis of non-B, non-C hepatocellular carcinoma: a large retrospective multicenter cohort study. J Gastroenterol. 2015;50:350–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Imamura Y, Uto H, Hiramine Y, et al. Increasing prevalence of diabetes mellitus in association with fatty liver in a Japanese population. J Gastroenterol. 2014;49:1406–13.

    Article  CAS  PubMed  Google Scholar 

  7. Völzke H. Multicausality in fatty liver disease: is there a rationale to distinguish between alcoholic and non-alcoholic origin? World J Gastroenterol. 2012;18:3492–501.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Scaglioni F, Ciccia S, Marino M, et al. ASH and NASH. Dig Dis. 2011;29:202–10.

    Article  CAS  PubMed  Google Scholar 

  9. Bralet MP, Régimbeau JM, Pineau P, et al. Hepatocellular carcinoma occurring in nonfibrotic liver: epidemiologic and histopathologic analysis of 80 French cases. Hepatology. 2000;32:200–4.

    Article  CAS  PubMed  Google Scholar 

  10. Michitaka K, Nishiguchi S, Aoyagi Y, et al. Etiology of liver cirrhosis in Japan: a nationwide survey. J Gastroenterol. 2010;45:86–94.

    Article  PubMed  Google Scholar 

  11. 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. 2010;45:960–7.

    Article  CAS  PubMed  Google Scholar 

  12. Kleiner DE, Brunt EM, Van Natta M, et al. Nonalcoholic steatohepatitis clinical research network. Related articles: design and validation of histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41:1313–21.

    Article  PubMed  Google Scholar 

  13. Tobari M, Hashimoto E, Yatsuji S, et al. Imaging of nonalcoholic steatohepatitis: advantages and pitfalls of ultrasonography and computed tomography. Intern Med. 2009;48:739–46.

    Article  PubMed  Google Scholar 

  14. Neuschwander-Tetri BA, Caldwell SH. Nonalcoholic steatohepatitis: summary of an AASLD single topic conference. Hepatology. 2003;37:1202–19.

    Article  PubMed  Google Scholar 

  15. Tsutsumi M. The history of the diagnostic criteria for alcoholic liver disease and current status of alcoholic liver disease in Japan. Nihon Shokakibyo Gakkai Zasshi (in Japanese). 2012;109:1509–17.

    Google Scholar 

  16. Minagawa M, Ikai I, Matsuyama Y, et al. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Arii S, Sata M, Sakamoto M, et al. Management of hepatocellular carcinoma: report of consensus meeting in the 45th annual meeting of the Japan Society of Hepatology. Hepatol Res. 2010;40:667–85.

    Article  PubMed  Google Scholar 

  18. Mannucci E, Bardini G, Ognibene A, et al. Comparison of ADA and WHO screening methods for diabetes mellitus in obese patients. American Diabetes Association. Diabet Med. 1999;16:579–85.

    Article  CAS  PubMed  Google Scholar 

  19. Brunt EM, Janney CG, Di Bisceglie AM, et al. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol. 1999;94:2467–74.

    Article  CAS  PubMed  Google Scholar 

  20. Brunt EM, Kleiner DE, Wilson LA, et al. NASH Clinical Research Network (CRN). Nonalcoholic fatty liver disease (NAFLD) activity score and the histopathologic diagnosis in NAFLD: distinct clinicopathologic meanings. Hepatology. 2011;53:810–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Shimada M, Hashimoto E, Kaneda H, et al. Nonalcoholic steatohepatitis: risk factors for liver fibrosis. Hepatol Res. 2002;24:429–38.

    Article  PubMed  Google Scholar 

  22. Tokushige K, Hashimoto E, Horie Y, et al. Hepatocellular carcinoma based on cryptogenic liver disease: the most common non-viral hepatocellular carcinoma in patients aged over 80 years. Hepatol Res. 2015;45:441–7.

    Article  PubMed  Google Scholar 

  23. Bonafe M, Barbi C, Storci G, et al. What studies on human longevity tell us about the risk for cancer in the oldest old: data and hypotheses on the genetics and immunology of centenarians. Exp Gerontol. 2002;37:1263–71.

    Article  CAS  PubMed  Google Scholar 

  24. Maynard S, Schurman SH, Harboe C, et al. Base excision repair of oxidative DNA damage and association with cancer and aging. Carcinogenesis. 2009;30:2–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Yasui K, Hashimoto E, Komorizono Y, et al. Characteristics of patients with nonalcoholic steatohepatitis who develop hepatocellular carcinoma. Clin Gastroenterol Hepatol. 2011;9:428–33.

    Article  PubMed  Google Scholar 

  26. Marrero JA, Feng Z, Wang Y, et al. Alpha-fetoprotein, des-gamma carboxyprothrombin, and lectin-bound alpha-fetoprotein in early hepatocellular carcinoma. Gastroenterology. 2009;137:110–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Hashimoto E, Tokushige K. Hepatocellular carcinoma in non-alcoholic steatohepatitis: growing evidence of an epidemic? Hepatol Res. 2012;42:1–14.

    Article  PubMed  Google Scholar 

  28. 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 

  29. Ascha MS, Hanouneh IA, Lopez R, et al. The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. Hepatology. 2010;51:1972–8.

    Article  PubMed  Google Scholar 

  30. Poon RT, Fan ST, Ng IO, et al. Different risk factors and prognosis for early and late intrahepatic recurrence after resection of hepatocellular carcinoma. Cancer. 2000;1(89):500–7.

    Article  Google Scholar 

  31. Takuma Y, Nouso K. Nonalcoholic steatohepatitis-associated hepatocellular carcinoma: our case series and literature review. World J Gastroenterol. 2010;28(16):1436–41.

    Article  Google Scholar 

  32. Hashizume H, Sato K, Takagi H, et al. Primary liver cancers with nonalcoholic steatohepatitis. Eur J Gastroenterol Hepatol. 2007;19:827–34.

    Article  PubMed  Google Scholar 

  33. Ariizumi S, Katagiri S, Katsuragawa H, et al. Sectionectomy is suitable for patients with T2 hepatocellular carcinoma according to the modified International Union Against Cancer TNM classification. Dig Surg. 2007;24:342–8.

    Article  PubMed  Google Scholar 

  34. Kamiyama T, Nakanishi K, Yokoo H, et al. Recurrence patterns after hepatectomy of hepatocellular carcinoma: implication of Milan criteria utilization. Ann Surg Oncol. 2009;16:1560–71.

    Article  PubMed  Google Scholar 

  35. Shah SA, Greig PD, Gallinger S, et al. Factors associated with early recurrence after resection for hepatocellular carcinoma and outcomes. J Am Coll Surg. 2006;202:275–83.

    Article  PubMed  Google Scholar 

  36. Kudo A, Tanaka S, Ban D, et al. Alcohol consumption and recurrence of non-B or non-C hepatocellular carcinoma after hepatectomy: a propensity score analysis. J Gastroenterol. 2014;49:1352–61.

    Article  CAS  PubMed  Google Scholar 

  37. Ekstedt M, Franzén LE, Holmqvist M, et al. Alcohol consumption is associated with progression of hepatic fibrosis in non-alcoholic fatty liver disease. Scand J Gastroenterol. 2009;44:366–74.

    Article  CAS  PubMed  Google Scholar 

  38. Zhang XQ, Xu CF, Yu CH, et al. Role of endoplasmic reticulum stress in the pathogenesis of nonalcoholic fatty liver disease. World J Gastroenterol. 2014;20:1768–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Kojima S, Kuo TF, Tatsukawa H, et al. Induction of cross-linking and silencing of Sp1 by transglutaminase during liver injury in ASH and NASH via different ER stress pathways. Dig Dis. 2010;28:715–21.

    Article  PubMed  Google Scholar 

  40. Ohhira M, Ohtake T, Saito H, et al. Increase of serum des-gamma-carboxy prothrombin in alcoholic liver disease without hepatocellular carcinoma. Alcohol Clin Exp Res. 1999;23(4 Suppl):67S–70S.

    Article  CAS  PubMed  Google Scholar 

  41. Ohhira M, Saito H, Suzuki Y, et al. A variant of des-gamma-carboxy prothrombin was increased in alcoholic liver disease without hepatocellular carcinoma. Alcohol Clin Exp Res. 2001;25(6 Suppl):46S–50S.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Dr. Shimizu Satoru (Tokyo Women’s Medical University) supported the statistical analysis.

Author information

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, Tomomi Kogiso & Etsuko Hashimoto

  2. Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, Japan

    Hideyuki Hyogo & Kazuaki Chayama

  3. Department of Hepatology, Sapporo Kosei General Hospital, Hokkaido, Japan

    Tomoaki Nakajima, Yoshiyasu Karino & Joji Toyota

  4. Department of Gastroenterology and Hepatology, Kochi Medical School, Kochi, Japan

    Masafumi Ono, Kensuke Munekage & Toshiji Saibara

  5. Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan

    Takumi Kawaguchi, Ryoko Kuromatsu & Takuji Torimura

  6. Department of Gastroenterology, Faculty of Medicine, Oita University, Oita, Japan

    Koichi Honda & Masataka Seike

  7. Division of Hepatology, Liver Center, Saga Medical School, Saga, Japan

    Yuichiro Eguchi, Satoshi Oeda & Hirokazu Takahashi

  8. Department of Gastroenterology, National Center for Global Health and Medicine, Tokyo, Japan

    Yuichi Nozaki, Mikio Yanase & Naohiko Masaki

  9. General Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan

    Miwa Kawanaka & Ken Nishino

  10. Center for Digestive and Liver Diseases, Nara City Hospital, Nara, Japan

    Saiyu Tanaka, Kohjiro Mori & Kazuyuki Kanemasa

  11. Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Yokohama, Kanagawa, Japan

    Kento Imajo, Yuji Ogawa & Atsushi Nakajima

  12. Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Yoshio Sumida, Yuya Seko & Yoshito Itoh

  13. Department of Gastroenterology and Hepatology, Osaka University, Graduate School of Medicine, Osaka, Japan

    Yoshihiro Kamada & Tetsuo Takehara

  14. Department of Gastroenterology, Osaka City Juso Hospital, Osaka, Japan

    Hideki Fujii

  15. Department of Gastroenterology, Nayoro City General Hospital, Hokkaido, Japan

    Yasuaki Suzuki

Authors
  1. Katsutoshi Tokushige
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Corresponding author

Correspondence to Katsutoshi Tokushige.

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Financial support

The authors state that there is no conflict of interest related to this study. This work was supported in part by a grant-in-aid from the Ministry of Health, Labour and Welfare of Japan.

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

535_2015_1129_MOESM1_ESM.pptx

Supplementary Fig. S1. (A–C) The relationship between survival rate and serum albumin (A), total bilirubin (B), and PT (%) (C) in the ALD-HCC group. These serum makers, factors of the Child-Pugh score, influenced the survival rate. (PPTX 114 kb)

535_2015_1129_MOESM2_ESM.pptx

Supplementary Fig. S2. (A, B) The relationship between the recurrence rate and AFP (A) and DCP (B). According to the grade of AFP, the recurrence rates were markedly different, but this was not clear with DCP. The recurrence of HCC in cases with 40 mAU/ml < DCP ≤ 100 mAU/ml was not so different from that of HCC ≤ 40 mAU/ml (PPTX 63 kb)

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Tokushige, K., Hyogo, H., Nakajima, T. et al. Hepatocellular carcinoma in Japanese patients with nonalcoholic fatty liver disease and alcoholic liver disease: multicenter survey. J Gastroenterol 51, 586–596 (2016). https://doi.org/10.1007/s00535-015-1129-1

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  • DOI: https://doi.org/10.1007/s00535-015-1129-1

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