Journal of Gastroenterology

, Volume 48, Issue 4, pp 515–525

Clinicopathological features of liver injury in patients with type 2 diabetes mellitus and comparative study of histologically proven nonalcoholic fatty liver diseases with or without type 2 diabetes mellitus

  • Toshihide Shima
  • Hirofumi Uto
  • Kohjiro Ueki
  • Toshinari Takamura
  • Yutaka Kohgo
  • Sumio Kawata
  • Kohichiroh Yasui
  • Hyohun Park
  • Naoto Nakamura
  • Tatsuaki Nakatou
  • Nobuyoshi Tanaka
  • Atsushi Umemura
  • Masayuki Mizuno
  • Junko Tanaka
  • Takeshi Okanoue
Original Article—Liver, Pancreas, and Biliary Tract

DOI: 10.1007/s00535-012-0653-5

Cite this article as:
Shima, T., Uto, H., Ueki, K. et al. J Gastroenterol (2013) 48: 515. doi:10.1007/s00535-012-0653-5



The Japan Society of Diabetes Mellitus reported that the leading cause of death in patients with diabetes mellitus (DM) was chronic liver disease; however, there are limited studies investigating the cause of liver injury in these patients. Our study aimed to clarify the clinicopathological features of liver injury and the characteristics of nonalcoholic fatty liver disease (NAFLD) in DM patients.


In total, 5,642 DM patients and 365 histologically proven NAFLD patients were enrolled. Clinical and laboratory parameters and liver biopsy results were, respectively, recorded and analyzed for the two sets of patients.


Positivity rates for Hepatitis B surface antigens (HBsAg) and anti-hepatitis C virus antibodies (anti-HCV Ab) were 1.7 and 5.1 %, respectively. The proportion of drinkers consuming 20–59 g and ≥60 g alcohol daily was 14.9 and 4.3 %, respectively. The percentage of DM patients with elevated serum alanine aminotransferase (ALT) levels (≥31 IU/L) was 28.6 %. Alcohol consumption had no significant effect on serum ALT levels. Seventy-two percent of HBsAg-positive patients were serum hepatitis B virus (HBV)-DNA negative, whereas 10 % exhibited high levels of the same (>4.0 log copies/ml). Thirty-eight percent of anti-HCV Ab-positive patients were serum HCV-RNA negative. Among the NAFLD patients, the frequencies of NASH and advanced stage NASH were significantly higher in male DM patients than in male patients without DM.


Although HBsAg- and anti-HCV Ab-positivity rates were high in our Japanese DM patients, a majority of liver injuries could be associated with NAFLD/nonalcoholic steatohepatitis.


Nonalcoholic fatty liver diseaseNonalcoholic steatohepatitisDiabetes mellitusHepatitis virus carrierAlcoholic liver diseaseNationwide study



Hepatocellular carcinoma


Nonalcoholic fatty liver disease


Diabetes mellitus


Nonalcoholic steatohepatitis


Hepatitis B virus


Hepatitis C virus


Aspartate aminotransferase


Alanine aminotransferase


Gamma glutamyl transpeptidase


Fasting plasma glucose


The homeostasis model assessment of insulin resistance index


Hepatitis B surface antigen

anti-HBc Ab

Anti-hepatitis B core antibody

anti-HCV Ab

Anti-hepatitis C virus antibody


Hepatitis B virus-deoxyribonucleic acid


Hepatitis C virus-ribonucleic acid


Odds ratio


Confidence interval

Copyright information

© Springer 2012

Authors and Affiliations

  • Toshihide Shima
    • 1
  • Hirofumi Uto
    • 2
  • Kohjiro Ueki
    • 3
  • Toshinari Takamura
    • 4
  • Yutaka Kohgo
    • 5
  • Sumio Kawata
    • 6
  • Kohichiroh Yasui
    • 7
  • Hyohun Park
    • 8
  • Naoto Nakamura
    • 9
  • Tatsuaki Nakatou
    • 10
  • Nobuyoshi Tanaka
    • 11
  • Atsushi Umemura
    • 1
  • Masayuki Mizuno
    • 1
  • Junko Tanaka
    • 12
  • Takeshi Okanoue
    • 1
  1. 1.Department of Gastroenterology and HepatologySaiseikai Suita HospitalSuitaJapan
  2. 2.Digestive and Life-style Related DiseaseKagoshima University Graduate School of Medical and Dental SciencesKagoshimaJapan
  3. 3.Diabetes and Metabolic Diseases, Graduate School of MedicineThe University of TokyoTokyoJapan
  4. 4.Disease Control and HomeostasisKanazawa University Graduate School of Medical ScienceKanazawaJapan
  5. 5.Gastroenterology and Hematology/Oncology, Department of MedicineAsahikawa Medical CollegeAsahikawaJapan
  6. 6.GastroenterologyYamagata University Faculty of MedicineYamagataJapan
  7. 7.Molecular Gastroenterology and HepatologyKyoto Prefectural University of MedicineKyotoJapan
  8. 8.Diabetes and Metabolic DiseasesSaiseikai Suita HospitalSuitaJapan
  9. 9.Endocrinology and MetabolismKyoto Prefectural University of MedicineKyotoJapan
  10. 10.Diabetes CenterOkayama Saiseikai General HospitalOkayamaJapan
  11. 11.GastroenterologyFukui-ken Saiseikai HospitalFukuiJapan
  12. 12.Department of Epidemiology, Infectious Disease Control and PreventionHiroshima University Graduate School of Biomedical SciencesHiroshimaJapan