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Journal of Gastroenterology

, Volume 54, Issue 4, pp 339–346 | Cite as

TLL1 variant associated with development of hepatocellular carcinoma after eradication of hepatitis C virus by interferon-free therapy

  • Etsuko Iio
  • Kentaro Matsuura
  • Noritomo Shimada
  • Masanori Atsukawa
  • Norio Itokawa
  • Hiroshi Abe
  • Keizo Kato
  • Koichi Takaguchi
  • Tomonori Senoh
  • Yuichiro Eguchi
  • Hideyuki Nomura
  • Kai Yoshizawa
  • Jong-Hon Kang
  • Takeshi Matsui
  • Noboru Hirashima
  • Atsunori Kusakabe
  • Tomokatsu Miyaki
  • Kei Fujiwara
  • Kayoko Matsunami
  • Susumu Tsutsumi
  • Katsuhiko Iwakiri
  • Yasuhito TanakaEmail author
Original Article—Liver, Pancreas, and Biliary Tract
  • 235 Downloads

Abstract

Background

The aim of this study is to ascertain whether the TLL1 variant at rs17047200 is associated with the development of HCC after achieving sustained virological response (SVR) by interferon (IFN)-free therapy for chronic hepatitis C (CHC).

Methods

A total of 1029 Japanese CHC patients with the following inclusion criteria were enrolled: (i) achieved SVR by IFN-free therapy, (ii) followed up at least 1 year from the end of treatment (EOT) (median 104 weeks), (iii) no history of hepatocellular carcinoma (HCC) by 1 year from the EOT.

Results

Nineteen patients developed HCC (HCC group) and 1010 did not (non-HCC group). The proportion of rs17047200 AT/TT was significantly higher in the HCC group than the non-HCC group (47.4% vs. 20.1%, P = 0.008). Multivariate analysis showed that higher levels of α-fetoprotein, FIB-4 and rs17047200 AT/TT were independent risk factors for developing HCC (HR = 3.22, P = 0.021 for α-fetoprotein > 4.6 ng/ml; HR = 3.89, P = 0.036 for FIB-4 > 2.67; HR = 2.80, P = 0.026 for rs17047200 AT/TT). Cumulative incidence of HCC was significantly higher in patients with rs17047200 AT/TT than in those with AA (P = 0.006). Comparing clinical characteristics according to the TLL1 genotypes, patients with rs17047200 AT/TT had significantly lower platelet counts and higher levels of FIB-4 than those with AA (P = 0.011 and 0.032, respectively).

Conclusions

The TLL1 variant was independently associated with HCC development after HCV eradication by IFN-free regimen. It might be involved in hepatic fibrogenesis and thereby carcinogenesis.

Keywords

HCV IFN-free therapy TLL1 SVR HCC DAA 

Abbreviations

AFP

α-Fetoprotein

ALT

Alanine aminotransaminase

AST

Aspartate aminotransferase

CHC

Chronic hepatitis C

DAA

Direct-acting antiviral agent

EOT

End of treatment

HCC

Hepatocellular carcinoma

HCV

Hepatitis C virus

IFN

Interferon

LC

Liver cirrhosis

SNP

Single nucleotide polymorphism

SVR

Sustained virological responses

Notes

Acknowledgements

The authors would like to thank Shintaro Ogawa and Kyoko Ito of Nagoya City University Graduate School of Medical Sciences.

Funding

This research was supported by the Research Program on Hepatitis from the Japan Agency for Medical Research and Development (AMED) to Yasuhito Tanka, project code: JP18fk0210001h0003 and the JSPS KAKENHI Grant-in-Aid for Young Scientists (A) to Etsuko Iio, Grant Number: 17K15960

Compliance with ethical standards

Conflict of interest

Yasuhito Tanaka is currently conducting research sponsored by Chugai Pharmaceutical Co., Ltd and has received honoraria from Janssen Pharmaceutical K.K, and Gilead Sciences. Masanori Atsukawa is currently conducting research sponsored by MSD K.K., and AbbVie Inc., and has received honoraria from MSD K.K. and Gilead Sciences. Koichi Takaguchi has received honoraria from Gilead Sciences, MSD K.K., AbbVie Inc., Bristol-Myers Squibb, and Astrazeneka KK. Hideyuki Nomura has received honoraria from Gilead Sciences. The other authors declare no conflicts of interest.

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Copyright information

© Japanese Society of Gastroenterology 2018

Authors and Affiliations

  • Etsuko Iio
    • 1
  • Kentaro Matsuura
    • 1
  • Noritomo Shimada
    • 2
  • Masanori Atsukawa
    • 3
  • Norio Itokawa
    • 4
  • Hiroshi Abe
    • 5
  • Keizo Kato
    • 5
  • Koichi Takaguchi
    • 6
  • Tomonori Senoh
    • 6
  • Yuichiro Eguchi
    • 7
  • Hideyuki Nomura
    • 8
  • Kai Yoshizawa
    • 9
  • Jong-Hon Kang
    • 10
  • Takeshi Matsui
    • 10
  • Noboru Hirashima
    • 11
  • Atsunori Kusakabe
    • 12
  • Tomokatsu Miyaki
    • 13
  • Kei Fujiwara
    • 1
  • Kayoko Matsunami
    • 1
  • Susumu Tsutsumi
    • 1
  • Katsuhiko Iwakiri
    • 3
  • Yasuhito Tanaka
    • 1
    Email author
  1. 1.Nagoya City University, Graduate School of Medical SciencesNagoyaJapan
  2. 2.Ootakanomori HospitalKashiwaJapan
  3. 3.Nippon Medical School HospitalTokyoJapan
  4. 4.Nippon Medical School Chiba Hokusoh HospitalChibaJapan
  5. 5.Shinmatsudo Central General HospitalChibaJapan
  6. 6.Kagawa Prefectural Central HospitalTakamatsuJapan
  7. 7.Saga University HospitalSagaJapan
  8. 8.Shin-Kokura HospitalKitakyushuJapan
  9. 9.Machida Municipal HospitalTokyoJapan
  10. 10.Teine Keijinkai HospitalSapporoJapan
  11. 11.National Hospital Organization Nagoya Medical CenterNagoyaJapan
  12. 12.Japanese Red Cross Nagoya Daini HospitalNagoyaJapan
  13. 13.Toyokawa City HospitalToyokawaJapan

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