J Gastroenterol Hepatol. 2018 Aug 30. doi: 10.1111/jgh.14454. [Epub ahead of print]
HLA-DQA1/DRB1 Polymorphism is Associated with the Development of Hepatocellular Carcinoma during Entecavir Treatment.
Kozuka R1, Enomoto M1, Sato-Matsubara M1, Yoshida K1, Motoyama H1, Hagihara A1, Fujii H1, Uchida-Kobayashi S1, Morikawa H1, Tamori A1, Kawada N1, Murakami Y1.
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1
Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Abstract
BACKGROUND & 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 (NA)-naïve 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 × 103 /mm3 ; p = 0.0007), α-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; HR, 4.907; 95% CI, 1.407 - 17.113) and cirrhosis (p = 0.019; HR, 4.789; 95% CI, 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.
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KEYWORDS:
Hepatocellular carcinoma; human leukocyte antigen; liver cirrhosis; single-nucleotide polymorphism