Journal of Gastroenterology

, Volume 47, Issue 7, pp 834–844 | Cite as

IL28B polymorphism is associated with fatty change in the liver of chronic hepatitis C patients

  • Mayu Ohnishi
  • Masataka Tsuge
  • Tomohiko Kohno
  • Yizhou Zhang
  • Hiromi Abe
  • Hideyuki Hyogo
  • Yuki Kimura
  • Daiki Miki
  • Nobuhiko Hiraga
  • Michio Imamura
  • Shoichi Takahashi
  • Hidenori Ochi
  • C. Nelson Hayes
  • Shinji Tanaka
  • Koji Arihiro
  • Kazuaki Chayama
Original Article—Liver, Pancreas, and Biliary Tract

Abstract

Background

Several single nucleotide polymorphisms (SNPs) within the interleukin 28B (IL28B) locus are associated with sustained viral response in chronic hepatitis C (HCV) patients who were treated with pegylated interferon (PEG-IFN) plus ribavirin (RBV) combination therapy. Recently, an association between γ-GTP level and IL28B genotype was identified. In this study, the relationship between IL28B genotype and liver steatosis was analyzed.

Methods

One hundred fifty-three patients who underwent liver biopsy before PEG-IFN plus RBV combination therapy were enrolled. The level of liver steatosis was measured using a BIOREVO BZ-9000 microscope, and the proportion of fatty change and clear cell change were calculated using Dynamic cell count BZ-H1C software. IL28B SNP genotype (rs8099917) was determined using the Invader Assay.

Results

Vesicular change was significantly associated with body mass index (BMI), HCV RNA titer, serum aspartate aminotransferase, γ-GTP, IL28B genotype and liver fibrosis level (P < 0.05). Clear cell change was significantly associated with serum aspartate aminotransferase, γ-GTP and IL28B genotype by univariate logistic regression analysis (P < 0.05). Under multiple logistic regression, IL28B genotype (ORadj = 8.158; 95% CI 2.412–27.589), liver fibrosis (ORadj = 2.541; 95% CI 1.040–6.207) and BMI (ORadj = 1.147; 95% CI 1.011–1.301) were significant independent factors for vesicular change and IL28B genotype (ORadj = 3.000; 95% CI 1.282–7.019) for clear cell change.

Conclusion

In this study, a new quantitative method to objectively evaluate hepatic steatosis was described. IL28B genotypes were significantly associated with both vesicular and clear cell changes of livers in chronic hepatitis C patients.

Keywords

HCV Core substitution IL28B Fatty change SNP 

Abbreviations

HCV

Hepatitis C virus

IFN

Interferon

PEG-IFN

Pegylated interferon

RBV

Ribavirin

ISDR

IFN-sensitivity determining region

IL28

Interleukin 28

SNP

Single nucleotide polymorphism

BMI

Body mass index

γ-GTP

Gamma glutamyl transpeptidase

aa

Amino acid

HOMA-IR

Homeostasis model assessment of insulin resistance

Notes

Acknowledgments

The authors thank Rie Akiyama for technical assistance and Aya Furukawa for clerical assistance. This study was supported by Grants-in-Aid for Scientific Research and Development from the Ministry of Education, Sports, Culture and Technology, and in part by a Grant-in-Aid from the Ministry of Health, Labor and Welfare of Japan, and was carried out at the Research Center for Molecular Medicine, Faculty of Medicine, Hiroshima University, and the Analysis Center of Life Science, Hiroshima University.

Conflict of interest

None.

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Copyright information

© Springer 2012

Authors and Affiliations

  • Mayu Ohnishi
    • 1
    • 2
  • Masataka Tsuge
    • 1
    • 2
    • 3
  • Tomohiko Kohno
    • 1
    • 2
  • Yizhou Zhang
    • 1
    • 2
  • Hiromi Abe
    • 1
    • 2
  • Hideyuki Hyogo
    • 1
    • 2
  • Yuki Kimura
    • 1
    • 2
  • Daiki Miki
    • 1
    • 2
    • 4
  • Nobuhiko Hiraga
    • 1
    • 2
  • Michio Imamura
    • 1
    • 2
  • Shoichi Takahashi
    • 1
    • 2
  • Hidenori Ochi
    • 1
    • 2
    • 4
  • C. Nelson Hayes
    • 1
    • 2
  • Shinji Tanaka
    • 1
  • Koji Arihiro
    • 5
  • Kazuaki Chayama
    • 1
    • 2
    • 4
    • 6
  1. 1.Programs for Biomedical Research, Division of Frontier Medical Science, Department of Gastroenterology and Metabolism, Graduate School of Biomedical SciencesHiroshima UniversityHiroshimaJapan
  2. 2.Liver Research Project CenterHiroshima UniversityHiroshimaJapan
  3. 3.Natural Science Center for Basic Research and DevelopmentHiroshima UniversityHiroshimaJapan
  4. 4.Laboratory for Digestive Diseases, Center for Genomic MedicineRIKENHiroshimaJapan
  5. 5.Department of PathologyHiroshima University HospitalHiroshimaJapan
  6. 6.Programs for Biomedical Research, Division of Frontier Medical Science, Department of Medical and Molecular Science, Graduate School of Biomedical SciencesHiroshima UniversityHiroshimaJapan

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