PMID- 30160782
OWN - NLM
STAT- MEDLINE
DCOM- 20191126
LR  - 20191126
IS  - 1440-1746 (Electronic)
IS  - 0815-9319 (Linking)
VI  - 34
IP  - 5
DP  - 2019 May
TI  - Association between HLA-DQA1/DRB1 polymorphism and development of hepatocellular 
      carcinoma during entecavir treatment.
PG  - 937-946
LID - 10.1111/jgh.14454 [doi]
AB  - BACKGROUND AND AIMS: It remains unclear whether there is an association between 
      single-nucleotide polymorphisms (SNPs) and development of hepatocellular 
      carcinoma (HCC) during entecavir (ETV) treatment in nucleos(t)ide analog-naive 
      patients with chronic hepatitis B virus infection. We investigated the risk 
      factors for HCC, especially host factors, during ETV treatment. METHODS: A total 
      of 127 Japanese patients undergoing ETV treatment were enrolled in this study. 
      Univariate and multivariate analyses for clinical factors, hepatic fibrosis 
      markers, and SNPs associated with HCC development were analyzed. RESULTS: A total 
      of 10 patients developed HCC during the follow-up period (median duration, 
      3.3 years). The 3-, 5-, and 7-year cumulative rates of HCC development were 4.8%, 
      10.6%, and 13.6%, respectively. Liver fibrosis (cirrhosis; P = 0.0005), age 
      (>/= 49 years; P = 0.0048), platelet count (</= 115 x 10/mm(3) ; P = 0.0007), 
      alpha-fetoprotein (>/= 8.0 ng/mL; P = 0.030), type IV collagen (>/= 200 ng/mL; 
      P = 0.043), fibrosis-4 index (>/= 4.14; P = 0.0006), and human leukocyte antigen 
      (HLA)-DQA1/DRB1-SNP (AA genotype; P = 0.0092) were significantly associated with 
      HCC development according to the log-rank test. In multivariate analysis, AA 
      genotype in the HLA-DQA1/DRB1 gene (P = 0.013; hazard ratio 4.907; 95% confidence 
      interval 1.407-17.113) and cirrhosis (P = 0.019; hazard ratio 4.789; 95% 
      confidence interval 1.296-17.689) were significantly associated with HCC 
      development. CONCLUSIONS: Our findings suggested that patients with AA genotype 
      in the HLA-DQA1/DRB1 gene or cirrhosis should be carefully followed up as a 
      population potentially at higher risk of HCC during ETV treatment.
CI  - (c) 2018 Journal of Gastroenterology and Hepatology Foundation and John Wiley & 
      Sons Australia, Ltd.
FAU - Kozuka, Ritsuzo
AU  - Kozuka R
AUID- ORCID: 0000-0002-0763-6760
AD  - Department of Hepatology, Osaka City University Graduate School of Medicine, 
      Osaka, Japan.
FAU - Enomoto, Masaru
AU  - Enomoto M
AD  - Department of Hepatology, Osaka City University Graduate School of Medicine, 
      Osaka, Japan.
FAU - Sato-Matsubara, Misako
AU  - Sato-Matsubara M
AD  - Department of Hepatology, Osaka City University Graduate School of Medicine, 
      Osaka, Japan.
FAU - Yoshida, Kanako
AU  - Yoshida K
AD  - Department of Hepatology, Osaka City University Graduate School of Medicine, 
      Osaka, Japan.
FAU - Motoyama, Hiroyuki
AU  - Motoyama H
AD  - Department of Hepatology, Osaka City University Graduate School of Medicine, 
      Osaka, Japan.
FAU - Hagihara, Atsushi
AU  - Hagihara A
AD  - Department of Hepatology, Osaka City University Graduate School of Medicine, 
      Osaka, Japan.
FAU - Fujii, Hideki
AU  - Fujii H
AD  - Department of Hepatology, Osaka City University Graduate School of Medicine, 
      Osaka, Japan.
FAU - Uchida-Kobayashi, Sawako
AU  - Uchida-Kobayashi S
AD  - Department of Hepatology, Osaka City University Graduate School of Medicine, 
      Osaka, Japan.
FAU - Morikawa, Hiroyasu
AU  - Morikawa H
AD  - Department of Hepatology, Osaka City University Graduate School of Medicine, 
      Osaka, Japan.
FAU - Tamori, Akihiro
AU  - Tamori A
AD  - Department of Hepatology, Osaka City University Graduate School of Medicine, 
      Osaka, Japan.
FAU - Kawada, Norifumi
AU  - Kawada N
AD  - Department of Hepatology, Osaka City University Graduate School of Medicine, 
      Osaka, Japan.
FAU - Murakami, Yoshiki
AU  - Murakami Y
AD  - Department of Hepatology, Osaka City University Graduate School of Medicine, 
      Osaka, Japan.
LA  - eng
GR  - 15K19345/Japan Society for the Promotion of Science/
GR  - JP 15K19345/JSPS KAKENHI/
PT  - Journal Article
DEP - 20180926
PL  - Australia
TA  - J Gastroenterol Hepatol
JT  - Journal of gastroenterology and hepatology
JID - 8607909
RN  - 0 (HLA-DQ alpha-Chains)
RN  - 0 (HLA-DQA1 antigen)
RN  - 0 (HLA-DRB1 Chains)
RN  - 5968Y6H45M (entecavir)
RN  - 5Z93L87A1R (Guanine)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Carcinoma, Hepatocellular/etiology/*genetics
MH  - Female
MH  - Fibrosis
MH  - *Genome-Wide Association Study
MH  - Genotype
MH  - Guanine/*analogs & derivatives/therapeutic use
MH  - HLA-DQ alpha-Chains/*genetics
MH  - HLA-DRB1 Chains/*genetics
MH  - Hepatitis B, Chronic/complications/*drug therapy/pathology
MH  - Humans
MH  - Liver/pathology
MH  - Liver Neoplasms/etiology/*genetics
MH  - Male
MH  - Middle Aged
MH  - Multivariate Analysis
MH  - Polymorphism, Single Nucleotide/*genetics
MH  - Risk Factors
MH  - Young Adult
OTO - NOTNLM
OT  - hepatocellular carcinoma
OT  - human leukocyte antigen
OT  - liver cirrhosis
OT  - single-nucleotide polymorphism
EDAT- 2018/08/31 06:00
MHDA- 2019/11/27 06:00
CRDT- 2018/08/31 06:00
PHST- 2018/04/21 00:00 [received]
PHST- 2018/08/14 00:00 [revised]
PHST- 2018/08/16 00:00 [accepted]
PHST- 2018/08/31 06:00 [pubmed]
PHST- 2019/11/27 06:00 [medline]
PHST- 2018/08/31 06:00 [entrez]
AID - 10.1111/jgh.14454 [doi]
PST - ppublish
SO  - J Gastroenterol Hepatol. 2019 May;34(5):937-946. doi: 10.1111/jgh.14454. Epub 
      2018 Sep 26.