Journal of Gastroenterology

, Volume 49, Issue 4, pp 748–754

IL28B minor allele is associated with a younger age of onset of hepatocellular carcinoma in patients with chronic hepatitis C virus infection

  • Masaya Sato
  • Naoya Kato
  • Ryosuke Tateishi
  • Ryosuke Muroyama
  • Norie Kowatari
  • Wenwen Li
  • Kaku Goto
  • Motoyuki Otsuka
  • Shuichiro Shiina
  • Haruhiko Yoshida
  • Masao Omata
  • Kazuhiko Koike
Original Article—Liver, Pancreas, and Biliary Tract

Abstract

Background

IL28B polymorphisms were shown to be associated with a response to peg-interferon-based treatment in chronic hepatitis C (CHC) and spontaneous clearance. However, little is known about how this polymorphism affects the course of CHC, including the development of hepatocellular carcinoma (HCC). We evaluated the influence of IL28B polymorphisms on hepatocarcinogenesis in CHC patients.

Methods

We genotyped the rs8099917 single-nucleotide polymorphism in 351 hepatitis C-associated HCC patients without history of IFN-based treatment, and correlated the age at onset of HCC in patients with each genotype.

Results

Frequencies of TT, TG, and GG genotypes were 74.3 % (261/351), 24.8 % (87/351), and 0.9 % (3/351), respectively. The mean ages at onset of HCC for TT, TG, and GG genotypes were 69.9, 67.5 and 66.8, respectively. In multivariate analysis, IL28B minor allele (TG and GG genotypes) was an independent risk factor for younger age at onset of HCC (P = 0.02) in males (P < 0.001) with higher body mass index (BMI; P = 0.009). The IL28B minor allele was also associated with a lower probability of having aspartate aminotransferase-to-platelet ratio index (APRI) >1.5 (minor vs. major, 46.7 vs. 58.6 %; P = 0.01), lower AST (69.1 vs. 77.7 IU/L, P = 0.02), lower ALT (67.8 vs. 80.9 IU/L, P = 0.002), higher platelet count (12.8 vs. 11.2 × 104/μL, P = 0.002), and higher prothrombin time (79.3 vs. 75.4 %, P = 0.002).

Conclusions

The IL28B minor allele was associated with lower inflammatory activity and less progressed fibrosis of the liver; however, it constituted a risk factor for younger-age onset of HCC in CHC patients.

Keywords

rs8099917 Hepatocarcinogenesis Interferon-λ Risk allele Fibrosis 

Abbreviations

AFP

α-Fetoprotein

APRI

Aminotransferase platelet ratio index

CHC

Chronic hepatitis C

GWAS

Genome-wide association study

HCC

Hepatocellular carcinoma

HCV

Hepatitis C virus

IL28B

Interleukin 28B

PCR

Polymerase chain reaction

peg-IFN

peg-Interferon

RIG- I

Retinoic acid-inducible gene-I

SNP

Single-nucleotide polymorphism

SVR

Sustained viral response

TLR3

Toll-like receptor 3

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Copyright information

© Springer Japan 2013

Authors and Affiliations

  • Masaya Sato
    • 1
  • Naoya Kato
    • 2
  • Ryosuke Tateishi
    • 1
  • Ryosuke Muroyama
    • 2
  • Norie Kowatari
    • 2
  • Wenwen Li
    • 2
  • Kaku Goto
    • 2
  • Motoyuki Otsuka
    • 1
  • Shuichiro Shiina
    • 1
  • Haruhiko Yoshida
    • 1
  • Masao Omata
    • 3
  • Kazuhiko Koike
    • 1
  1. 1.Department of Gastroenterology, Graduate School of MedicineThe University of TokyoTokyoJapan
  2. 2.Unit of Disease Control Genome Medicine, Institute of Medical ScienceThe University of TokyoTokyoJapan
  3. 3.Yamanashi Prefectural Hospital OrganizationKofuJapan

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