Journal of Gastroenterology

, Volume 54, Issue 1, pp 64–77 | Cite as

Hepatocellular carcinoma as a leading cause of cancer-related deaths in Japanese type 2 diabetes mellitus patients

  • Toshihide Shima
  • Hirofumi Uto
  • Kohjiro Ueki
  • Yutaka Kohgo
  • Kohichiroh Yasui
  • Naoto Nakamura
  • Tatsuaki Nakatou
  • Toshinari Takamura
  • Sumio Kawata
  • Kazuo Notsumata
  • Kyoko Sakai
  • Ryosuke Tateishi
  • Takeshi OkanoueEmail author
Original Article—Liver, Pancreas, and Biliary Tract



We reported a cross-sectional study on causes of liver injury in Japanese type 2 diabetes mellitus (T2D) patients (JG 2013). We assessed overall and cause-specific mortality risk during follow-up of patients enrolled in JG 2013.


This was a longitudinal, multicenter cohort study. Of the 5642 Japanese T2D patients who visited T2D clinics of nine hospitals in the original study, 3,999 patients were followed up for an average of 4.5 years. Expected deaths in T2D patients were estimated using age-specific mortality rates in the general population (GP) of Japan. Standardized mortality ratios (SMRs) were calculated to compare mortality between T2D patients and GP.


All-cancer mortality was significantly higher in T2D patients than in the GP [SMR 1.58, 95% confidence interval (CI) 1.33–1.87]. Among malignancies, hepatocellular carcinoma (HCC) conferred the highest mortality risk in T2D patients (SMR 3.57, 95% CI 2.41–5.10). HCC-associated mortality risk in T2D patients remained significantly high (SMR 2.56, 95% CI 1.64–3.97) after adjusting for high positivity rates of hepatitis B surface antigen (1.7%) and anti-hepatitis C virus (5.3%). In T2D patients with platelet counts < 200 × 103/μl, SMR of HCC increased from 3.57 to 6.58 (95% CI 4.34–9.58). T2D patients with platelet count > 200 × 103/μl showed no increase in mortality risk (SMR 0.68) of HCC.


HCC-associated mortality risk was the highest among all cancers in Japanese T2D patients. Regular follow-up may be important for T2D patients with platelet counts < 200 × 103/μl for early detection of HCC.


Type 2 diabetes mellitus Hepatocellular carcinoma Mortality risk Platelet count 



Hepatocellular carcinoma


Type 2 diabetes mellitus


Hepatitis B virus


Hepatitis C virus


Hepatitis B surface antigen

Anti-HCV Ab

Anti-hepatitis C virus antibody


Hazard ratio


Risk ratio


Standardized mortality ratio

95% CI

95% confidence interval



This work was supported by a Grant-in-Aid from the Ministry of Health, Labor, and Welfare, Japan (T. O., H20-Hepatitis-general-008) and the Research Program on Hepatitis from Japan Agency for Medical Research and Development, AMED (T.O.).

Compliance with ethical standards

Conflict of interest

N. Nakamura has received lecture fees from Ono Pharmaceutical Co., Taisho Pharmaceutical Co., and Astra Zeneka. All other authors have no conflicts to report.

Supplementary material

535_2018_1494_MOESM1_ESM.docx (82 kb)
Supplementary material 1 (DOCX 82 kb)


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Copyright information

© Japanese Society of Gastroenterology 2018

Authors and Affiliations

  • Toshihide Shima
    • 1
  • Hirofumi Uto
    • 2
  • Kohjiro Ueki
    • 3
  • Yutaka Kohgo
    • 4
  • Kohichiroh Yasui
    • 5
  • Naoto Nakamura
    • 6
  • Tatsuaki Nakatou
    • 7
  • Toshinari Takamura
    • 8
  • Sumio Kawata
    • 9
  • Kazuo Notsumata
    • 10
  • Kyoko Sakai
    • 11
    • 12
  • Ryosuke Tateishi
    • 13
  • Takeshi Okanoue
    • 1
    Email author
  1. 1.Department of Gastroenterology and HepatologySaiseikai Suita HospitalSuitaJapan
  2. 2.Department of Digestive and Lifestyle DiseasesKagoshima University Graduate School of Medical and Dental SciencesKagoshimaJapan
  3. 3.Department of Diabetes and Metabolic Diseases, Graduate School of MedicineThe University of TokyoTokyoJapan
  4. 4.Division of Gastroenterology and Hematology/Oncology, Department of MedicineAsahikawa Medical CollegeAsahikawaJapan
  5. 5.Department of Molecular Gastroenterology and HepatologyKyoto Prefectural University of MedicineKyotoJapan
  6. 6.Department of Endocrinology Diabetes and MetabolismKyoto Prefectural University of MedicineKyotoJapan
  7. 7.Diabetes CenterOkayama Saiseikai General HospitalOkayamaJapan
  8. 8.Department of Endocrinology and MetabolismKanazawa University Graduate School of Medical ScienceKanazawaJapan
  9. 9.Department of GastroenterologyYamagata University Faculty of MedicineYamagataJapan
  10. 10.Department of GastroenterologyFukui-ken Saiseikai HospitalFukuiJapan
  11. 11.Department of Clinical LaboratorySaiseikai Suita HospitalSuitaJapan
  12. 12.Department of Health InformaticsKyoto University School of Public HealthKyotoJapan
  13. 13.Department of Gastroenterology, Graduate School of MedicineThe University of TokyoTokyoJapan

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