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Journal of Gastroenterology

, Volume 51, Issue 6, pp 586–596 | Cite as

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

  • Katsutoshi TokushigeEmail author
  • Hideyuki Hyogo
  • Tomoaki Nakajima
  • Masafumi Ono
  • Takumi Kawaguchi
  • Koichi Honda
  • Yuichiro Eguchi
  • Yuichi Nozaki
  • Miwa Kawanaka
  • Saiyu Tanaka
  • Kento Imajo
  • Yoshio Sumida
  • Yoshihiro Kamada
  • Hideki Fujii
  • Yasuaki Suzuki
  • Tomomi Kogiso
  • Yoshiyasu Karino
  • Kensuke Munekage
  • Ryoko Kuromatsu
  • Satoshi Oeda
  • Mikio Yanase
  • Kohjiro Mori
  • Yuji Ogawa
  • Yuya Seko
  • Tetsuo Takehara
  • Yoshito Itoh
  • Atsushi Nakajima
  • Kazuyuki Kanemasa
  • Ken Nishino
  • Naohiko Masaki
  • Hirokazu Takahashi
  • Masataka Seike
  • Takuji Torimura
  • Toshiji Saibara
  • Joji Toyota
  • Kazuaki Chayama
  • Etsuko Hashimoto
Original Article—Liver, Pancreas, and Biliary Tract

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.

Keywords

Alcoholic liver disease Nonalcoholic fatty liver disease Hepatocellular carcinoma Survival Recurrence 

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

Notes

Acknowledgments

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

Compliance with ethical standards

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.

Supplementary material

535_2015_1129_MOESM1_ESM.pptx (115 kb)
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 (63 kb)
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)

References

  1. 1.
    GLOBOCAN2012: Estimated cancer incidence, mortality and prevalence worldwide 2012. http://globocan.iarc.fr/.
  2. 2.
    Journal of Health and Welfare Statistics. Health and Welfare Statistics Association 2013 Japan. 60, 51–75.Google Scholar
  3. 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.CrossRefGoogle Scholar
  4. 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.CrossRefPubMedGoogle Scholar
  5. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 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.CrossRefPubMedGoogle Scholar
  7. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Scaglioni F, Ciccia S, Marino M, et al. ASH and NASH. Dig Dis. 2011;29:202–10.CrossRefPubMedGoogle Scholar
  9. 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.CrossRefPubMedGoogle Scholar
  10. 10.
    Michitaka K, Nishiguchi S, Aoyagi Y, et al. Etiology of liver cirrhosis in Japan: a nationwide survey. J Gastroenterol. 2010;45:86–94.CrossRefPubMedGoogle Scholar
  11. 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.CrossRefPubMedGoogle Scholar
  12. 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.CrossRefPubMedGoogle Scholar
  13. 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.CrossRefPubMedGoogle Scholar
  14. 14.
    Neuschwander-Tetri BA, Caldwell SH. Nonalcoholic steatohepatitis: summary of an AASLD single topic conference. Hepatology. 2003;37:1202–19.CrossRefPubMedGoogle Scholar
  15. 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. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 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.CrossRefPubMedGoogle Scholar
  18. 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.CrossRefPubMedGoogle Scholar
  19. 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.CrossRefPubMedGoogle Scholar
  20. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Shimada M, Hashimoto E, Kaneda H, et al. Nonalcoholic steatohepatitis: risk factors for liver fibrosis. Hepatol Res. 2002;24:429–38.CrossRefPubMedGoogle Scholar
  22. 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.CrossRefPubMedGoogle Scholar
  23. 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.CrossRefPubMedGoogle Scholar
  24. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 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.CrossRefPubMedGoogle Scholar
  26. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Hashimoto E, Tokushige K. Hepatocellular carcinoma in non-alcoholic steatohepatitis: growing evidence of an epidemic? Hepatol Res. 2012;42:1–14.CrossRefPubMedGoogle Scholar
  28. 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.CrossRefPubMedGoogle Scholar
  29. 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.CrossRefPubMedGoogle Scholar
  30. 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.CrossRefGoogle Scholar
  31. 31.
    Takuma Y, Nouso K. Nonalcoholic steatohepatitis-associated hepatocellular carcinoma: our case series and literature review. World J Gastroenterol. 2010;28(16):1436–41.CrossRefGoogle Scholar
  32. 32.
    Hashizume H, Sato K, Takagi H, et al. Primary liver cancers with nonalcoholic steatohepatitis. Eur J Gastroenterol Hepatol. 2007;19:827–34.CrossRefPubMedGoogle Scholar
  33. 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.CrossRefPubMedGoogle Scholar
  34. 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.CrossRefPubMedGoogle Scholar
  35. 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.CrossRefPubMedGoogle Scholar
  36. 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.CrossRefPubMedGoogle Scholar
  37. 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.CrossRefPubMedGoogle Scholar
  38. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 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.CrossRefPubMedGoogle Scholar
  40. 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.CrossRefPubMedGoogle Scholar
  41. 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.PubMedGoogle Scholar

Copyright information

© Japanese Society of Gastroenterology 2015

Authors and Affiliations

  • Katsutoshi Tokushige
    • 1
    Email author
  • Hideyuki Hyogo
    • 2
  • Tomoaki Nakajima
    • 3
  • Masafumi Ono
    • 4
  • Takumi Kawaguchi
    • 5
  • Koichi Honda
    • 6
  • Yuichiro Eguchi
    • 7
  • Yuichi Nozaki
    • 8
  • Miwa Kawanaka
    • 9
  • Saiyu Tanaka
    • 10
  • Kento Imajo
    • 11
  • Yoshio Sumida
    • 12
  • Yoshihiro Kamada
    • 13
  • Hideki Fujii
    • 14
  • Yasuaki Suzuki
    • 15
  • Tomomi Kogiso
    • 1
  • Yoshiyasu Karino
    • 3
  • Kensuke Munekage
    • 4
  • Ryoko Kuromatsu
    • 5
  • Satoshi Oeda
    • 7
  • Mikio Yanase
    • 8
  • Kohjiro Mori
    • 10
  • Yuji Ogawa
    • 11
  • Yuya Seko
    • 12
  • Tetsuo Takehara
    • 13
  • Yoshito Itoh
    • 12
  • Atsushi Nakajima
    • 11
  • Kazuyuki Kanemasa
    • 10
  • Ken Nishino
    • 9
  • Naohiko Masaki
    • 8
  • Hirokazu Takahashi
    • 7
  • Masataka Seike
    • 6
  • Takuji Torimura
    • 5
  • Toshiji Saibara
    • 4
  • Joji Toyota
    • 3
  • Kazuaki Chayama
    • 2
  • Etsuko Hashimoto
    • 1
  1. 1.Department of Internal Medicine and GastroenterologyTokyo Women’s Medical UniversityTokyoJapan
  2. 2.Department of Gastroenterology and MetabolismHiroshima UniversityHiroshimaJapan
  3. 3.Department of HepatologySapporo Kosei General HospitalHokkaidoJapan
  4. 4.Department of Gastroenterology and HepatologyKochi Medical SchoolKochiJapan
  5. 5.Division of Gastroenterology, Department of MedicineKurume University School of MedicineFukuokaJapan
  6. 6.Department of Gastroenterology, Faculty of MedicineOita UniversityOitaJapan
  7. 7.Division of HepatologyLiver Center, Saga Medical SchoolSagaJapan
  8. 8.Department of GastroenterologyNational Center for Global Health and MedicineTokyoJapan
  9. 9.General Internal Medicine 2Kawasaki Hospital, Kawasaki Medical SchoolOkayamaJapan
  10. 10.Center for Digestive and Liver Diseases, Nara City HospitalNaraJapan
  11. 11.Department of Gastroenterology and HepatologyYokohama City University School of MedicineYokohamaJapan
  12. 12.Department of Gastroenterology and HepatologyKyoto Prefectural University of MedicineKyotoJapan
  13. 13.Department of Gastroenterology and HepatologyOsaka University, Graduate School of MedicineOsakaJapan
  14. 14.Department of GastroenterologyOsaka City Juso HospitalOsakaJapan
  15. 15.Department of GastroenterologyNayoro City General HospitalHokkaidoJapan

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