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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 Okanoue
Original Article—Liver, Pancreas, and Biliary Tract
  • 203 Downloads

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Keywords

Type 2 diabetes mellitus Hepatocellular carcinoma Mortality risk Platelet count 

Abbreviations

HCC

Hepatocellular carcinoma

T2D

Type 2 diabetes mellitus

HBV

Hepatitis B virus

HCV

Hepatitis C virus

HBsAg

Hepatitis B surface antigen

Anti-HCV Ab

Anti-hepatitis C virus antibody

HR

Hazard ratio

RR

Risk ratio

SMR

Standardized mortality ratio

95% CI

95% confidence interval

Notes

Acknowledgements

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
  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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