HLA-DQA1 / DRB1多态性与恩替卡韦治疗期间肝细胞癌的发展有关

StephenW

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.
Author information

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.

This article is protected by copyright. All rights reserved.
KEYWORDS:

Hepatocellular carcinoma; human leukocyte antigen; liver cirrhosis; single-nucleotide polymorphism

PMID:
    30160782
DOI:
    10.1111/jgh.14454

StephenW

J Gastroenterol Hepatol。 2018年8月30日doi：10.1111 / jgh.14454。 [提前打印]
HLA-DQA1 / DRB1多态性与恩替卡韦治疗期间肝细胞癌的发展有关。
Kozuka R1，En本M1，Sato-Matsubara M1，Yoshida K1，Motoyama H1，Hagihara A1，Fujii H1，Uchida-Kobayashi S1，Morikawa H1，Tamori A1，Kawada N1，Murakami Y1。
作者信息

1
    大阪市立大学医学研究科肝病学系，日本大阪。

抽象
背景与目的：

目前尚不清楚单核苷酸多态性（SNPs）与恩替卡韦（ETV）治疗期间核酸（t）类似物（NA） - 慢性乙型肝炎病毒感染患者的肝细胞癌（HCC）发展之间是否存在关联。我们在ETV治疗期间研究了HCC的风险因素，尤其是宿主因子。
方法：

共有127名日本接受ETV治疗的患者参加了本研究。分析了临床因素，肝纤维化标志物和与HCC发展相关的SNP的单变量和多变量分析。
结果：

在随访期间共有10名患者发生HCC（中位数持续时间为3。3年）。 HCC发展的3年，5年和7年累积率分别为4.8％，10.6％和13.6％。肝纤维化（肝硬化; p = 0.0005），年龄（≥49岁; p = 0.0048），血小板计数（≤115×103 / mm3; p = 0.0007），α-胎蛋白（≥8.0ng / ml; p = 0.030） ，IV型胶原（≥200ng/ mL; p = 0.043），纤维化-4指数（≥4.14; p = 0.0006）和人白细胞抗原（HLA）-DQA1 / DRB1-SNP（AA基因型; p = 0.0092）根据对数秩检验，与HCC发展显着相关。在多变量分析中，HLA-DQA1 / DRB1基因的AA基因型（p = 0.013; HR，4.907; 95％CI，1.407 - 17.113）和肝硬化（p = 0.019; HR，4.789; 95％CI，1.296 - 17.689）与HCC发展显着相关。
结论：

我们的研究结果表明，在ETV治疗期间，HLA-DQA1 / DRB1基因或肝硬化的AA基因型患者应该作为可能具有较高HCC风险的人群进行仔细随访。

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关键词：

肝细胞癌;人白细胞抗原;肝硬化;单核苷酸多态性

结论：
    30160782
DOI：
    10.1111 / jgh.14454