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

  • Iio, Etsuko1
  • Matsuura, Kentaro1
  • Shimada, Noritomo2
  • Atsukawa, Masanori3
  • Itokawa, Norio4
  • Abe, Hiroshi5
  • Kato, Keizo5
  • Takaguchi, Koichi6
  • Senoh, Tomonori6
  • Eguchi, Yuichiro7
  • Nomura, Hideyuki8
  • Yoshizawa, Kai9
  • Kang, Jong-Hon10
  • Matsui, Takeshi10
  • Hirashima, Noboru11
  • Kusakabe, Atsunori12
  • Miyaki, Tomokatsu13
  • Fujiwara, Kei1
  • Matsunami, Kayoko1
  • Tsutsumi, Susumu1
  • And 2 more
  • 1 Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan , Nagoya (Japan)
  • 2 Ootakanomori Hospital, Kashiwa, Japan , Kashiwa (Japan)
  • 3 Nippon Medical School Hospital, Tokyo, Japan , Tokyo (Japan)
  • 4 Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan , Chiba (Japan)
  • 5 Shinmatsudo Central General Hospital, Chiba, Japan , Chiba (Japan)
  • 6 Kagawa Prefectural Central Hospital, Takamatsu, Japan , Takamatsu (Japan)
  • 7 Saga University Hospital, Saga, Japan , Saga (Japan)
  • 8 Shin-Kokura Hospital, Kitakyushu, Japan , Kitakyushu (Japan)
  • 9 Machida Municipal Hospital, Tokyo, Japan , Tokyo (Japan)
  • 10 Teine Keijinkai Hospital, Sapporo, Japan , Sapporo (Japan)
  • 11 National Hospital Organization Nagoya Medical Center, Nagoya, Japan , Nagoya (Japan)
  • 12 Japanese Red Cross Nagoya Daini Hospital, Nagoya, Japan , Nagoya (Japan)
  • 13 Toyokawa City Hospital, Toyokawa, Japan , Toyokawa (Japan)
Published Article
Journal of Gastroenterology
Springer Japan
Publication Date
Oct 31, 2018
DOI: 10.1007/s00535-018-1526-3
Springer Nature


BackgroundThe 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).MethodsA 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.ResultsNineteen 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).ConclusionsThe 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.

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