TLL1 variant associated with development of hepatocellular carcinoma after eradication of hepatitis C virus by interferon-free therapy
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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).
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.
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).
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.
KeywordsHCV IFN-free therapy TLL1 SVR HCC DAA
Chronic hepatitis C
Direct-acting antiviral agent
End of treatment
Hepatitis C virus
Single nucleotide polymorphism
Sustained virological responses
The authors would like to thank Shintaro Ogawa and Kyoko Ito of Nagoya City University Graduate School of Medical Sciences.
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
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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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