Journal of Gastroenterology

, Volume 48, Issue 11, pp 1249–1258

Increased hepatic oxidative DNA damage in patients with nonalcoholic steatohepatitis who develop hepatocellular carcinoma

  • Shingo Tanaka
  • Koji Miyanishi
  • Masayoshi Kobune
  • Yutaka Kawano
  • Toshifumi Hoki
  • Tomohiro Kubo
  • Tsuyoshi Hayashi
  • Tsutomu Sato
  • Yasushi Sato
  • Rishu Takimoto
  • Junji Kato
Original Article—Liver, Pancreas, and Biliary Tract

DOI: 10.1007/s00535-012-0739-0

Cite this article as:
Tanaka, S., Miyanishi, K., Kobune, M. et al. J Gastroenterol (2013) 48: 1249. doi:10.1007/s00535-012-0739-0

Abstract

Background

The rate of onset of hepatocellular carcinoma (HCC) in patients with nonalcoholic steatohepatitis (NASH) has been reported recently to be comparable to that of patients with chronic hepatitis C. However, the precise mechanism contributing to carcinogenesis in the former remains unclear. Although increased oxidative stress is presumed to play a role in carcinogenesis in patients with NASH, this relationship remains to be directly proven. In this study, we investigated the involvement of oxidative DNA damage in hepatocarcinogenesis in patients with NASH.

Methods

Patients with nonalcoholic fatty liver disease who were treated at our university hospital were eligible for enrolment in the study(n = 49). The study cohort included 30 patients with NASH without HCC (NASH without HCC), six HCC patients with NASH (NASH–HCC), and 13 patients with simple steatosis. Quantitative immunohistochemistry with a KS-400 image analyzing system was used for 8-hydroxy-2′-deoxyguanosine (8-OHdG) detection.

Results

The 8-OHdG content in the liver tissue of NASH–HCC patients was significantly different from that in the other patients. The median immunostaining intensity was 8.605 in the NASH–HCC cases, which was significantly higher than that in the cases of NASH without HCC (4.845; P = 0.003). Multivariate analysis using hepatic 8-OHdG content as a factor in addition to age and fasting blood sugar revealed a significant difference in clinicopathological factors between NASH–HCC and NASH without HCC cases. Old age (P = 0.015) and high relative immunostaining intensity for intrahepatic 8-OHdG (P = 0.037) were identified as independent factors.

Conclusions

8-OHdG content in liver tissue may serve a marker of oxidative stress and could be a particularly useful predictor of hepatocarcinogenesis.

Keywords

Nonalcoholic steatohepatitisNonalcoholic fatty liver diseaseHepatocellular carcinomaOxidative DNA damage8-Hydroxy-2′-deoxyguanosine

Abbreviations

ALD

Alcoholic liver disease

APRI

Aspartate aminotransferase to platelet ratio index

4-HNE

4-Hydroxy-2-nonenal

NAFLD

Nonalcoholic fatty liver disease

NAS

NAFLD activity score

NASH

Nonalcoholic steatohepatitis

NBNC-HCC

Non-B non-C hepatocellular carcinoma

8-OHdG

8-Hydroxy-2′-deoxyguanosine

ROS

Reactive oxygen species

SS

Simple steatosis

Copyright information

© Springer Japan 2013

Authors and Affiliations

  • Shingo Tanaka
    • 1
  • Koji Miyanishi
    • 1
  • Masayoshi Kobune
    • 1
  • Yutaka Kawano
    • 1
  • Toshifumi Hoki
    • 1
  • Tomohiro Kubo
    • 1
  • Tsuyoshi Hayashi
    • 1
  • Tsutomu Sato
    • 1
  • Yasushi Sato
    • 1
  • Rishu Takimoto
    • 1
  • Junji Kato
    • 1
  1. 1.Fourth Department of Internal MedicineSapporo Medical University School of MedicineChuo-kuJapan