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

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 th...

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Published in:Journal of gastroenterology 2019-04, Vol.54 (4), p.339-346
Main Authors: Iio, Etsuko, Matsuura, Kentaro, Shimada, Noritomo, Atsukawa, Masanori, Itokawa, Norio, Abe, Hiroshi, Kato, Keizo, Takaguchi, Koichi, Senoh, Tomonori, Eguchi, Yuichiro, Nomura, Hideyuki, Yoshizawa, Kai, Kang, Jong-Hon, Matsui, Takeshi, Hirashima, Noboru, Kusakabe, Atsunori, Miyaki, Tomokatsu, Fujiwara, Kei, Matsunami, Kayoko, Tsutsumi, Susumu, Iwakiri, Katsuhiko, Tanaka, Yasuhito
Format: Article
Language:English
Subjects:
Abdominal Surgery
Adult
Aged
Aged, 80 and over
Antiviral Agents - administration & dosage
Biliary Tract
Biological response modifiers
Carcinogenesis
Carcinoma, Hepatocellular - epidemiology
Carcinoma, Hepatocellular - genetics
Care and treatment
Colorectal Surgery
Female
Follow-Up Studies
Gastroenterology
Genotype
Genotypes
Glycoproteins
Hepatitis
Hepatitis C
Hepatitis C virus
Hepatitis C, Chronic - drug therapy
Hepatitis C, Chronic - virology
Hepatocellular carcinoma
Hepatology
Hepatoma
Humans
Incidence
Interferon
Japan
Liver cancer
Liver Neoplasms - epidemiology
Liver Neoplasms - genetics
Male
Medicine
Medicine & Public Health
Middle Aged
Multivariate analysis
Original Article—Liver
Pancreas
Patients
Risk factors
Surgical Oncology
Tolloid-Like Metalloproteinases - genetics
Young Adult
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Summary: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.
ISSN:0944-1174
1435-5922
DOI:10.1007/s00535-018-1526-3