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The transition in the etiologies of hepatocellular carcinoma-complicated liver cirrhosis in a nationwide survey of Japan

  • Enomoto, Hirayuki1
  • Ueno, Yoshiyuki2
  • Hiasa, Yoichi3
  • Nishikawa, Hiroki1, 1
  • Hige, Shuhei4
  • Takikawa, Yasuhiro5
  • Taniai, Makiko6
  • Ishikawa, Toru7
  • Yasui, Kohichiroh8
  • Takaki, Akinobu9
  • Takaguchi, Koichi10
  • Ido, Akio11
  • Kurosaki, Masayuki12
  • Kanto, Tatsuya13
  • Nishiguchi, Shuhei1, 14
  • 1 Hyogo College of Medicine,
  • 2 Yamagata University,
  • 3 Ehime University Graduate School of Medicine,
  • 4 Sapporo Kosei General Hospital,
  • 5 Iwate Medical University,
  • 6 Tokyo Women’s Medical University,
  • 7 Saiseikai Niigata Daini Hospital,
  • 8 Kyoto Prefectural University of Medicine,
  • 9 Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences,
  • 10 Kagawa Prefectural Central Hospital,
  • 11 Kagoshima University Graduate School of Medical and Dental Sciences,
  • 12 Musashino Red Cross Hospital,
  • 13 Hepatitis Information Center, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine,
  • 14 Department of Gastroenterology, Kano General Hospital, 7-5-15, Tenjin-bashi, Kita-ku, Osaka, 531-0041 Japan
Published Article
Journal of Gastroenterology
Springer Singapore
Publication Date
Nov 20, 2020
DOI: 10.1007/s00535-020-01748-x
PMID: 33219410
PMCID: PMC7862502
PubMed Central


Background We recently reported the real-world changes in the etiologies of liver cirrhosis (LC) based on nationwide survey data and assessed the etiologies of LC with hepatocellular carcinoma (HCC). Methods Fifty-five participants from 68 institutions provided data on 23,637 patients with HCC-complicated LC. The changing trends in etiologies were assessed. We further analyzed the data from 29 hospitals that provided the annual number of newly identified HCC-complicated LC patients from 2008 to 2016 ( N = 9362) without any missing years and assessed the transition in the real number of newly identified HCC-complicated LC cases. Results In the overall cohort, hepatitis C virus (HCV) infection (60.3%) and hepatitis B virus (HBV) infection (12.9%) were the leading and third-most common causes of HCC-complicated LC in Japan, respectively. HCV infection was found to be the leading cause throughout Japan. The rate of viral hepatitis-related HCC decreased from 85.3 to 64.4%. Among non-viral etiologies, notable increases were observed in nonalcoholic steatohepatitis (NASH)-related HCC (from 1.5 to 7.2%) and alcoholic liver disease (ALD)-related HCC (from 8.5 to 18.6%). Regarding the real number of newly diagnosed patients, the number of patients with viral hepatitis-related HCC decreased, while the number of patients with non-viral HCC, particularly NASH-related HCC, increased. Conclusions Viral hepatitis has remained the main cause of HCC in Japan. However, the decrease in viral hepatitis-related HCC, particularly HCV-related HCC highly contributed to the etiological changes. In addition, the increased incidence of non-viral HCC, particularly NASH-related HCC, was involved in the changing etiologies of HCC-complicated LC in Japan. Electronic supplementary material The online version of this article (10.1007/s00535-020-01748-x) contains supplementary material, which is available to authorized users.

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