Division of Infectious Disease Pathology, Department of Microbiology and Infectious Disease, Kobe University Graduate School of Medicine, 7-5-1 Chuo-ku, Kobe, 650-0017, Japan.
Division of Gastroenterohepatology, Department of Internal Medicine, Dr. Sardjito Hospital, Faculty of Medicine, Gadjah Mada University/ Dr. Sardjito Hospital, Kesehatan Street No. 1, Sekip, Yogyakarta, 55281, Indonesia.
Virol J. 2017 Oct 23;14(1):201. doi: 10.1186/s12985-017-0865-7.
Occult hepatitis B infection (OBI) is defined as the presence of hepatitis B virus (HBV) DNA in the serum and/or liver in HBsAg-negative individuals. OBI is associated with the risk of viral transmission, especially in developing countries, and with progressive liver disease and reactivation in immunosuppressive patients. The objective of this study was to evaluate the relation of OBI to HLA-DP single nucleotide polymorphisms (SNPs) encoding antigen-binding sites for the immune response to HBV infection. As HLA-DP variants affect the mRNA expression of HLA-DPA1 and HLA-DPB1 in the liver, we hypothesised that high levels of HLA-DPA1 and HLA-DPB1 expression favour OBI development.
The study enrolled 456 Indonesian healthy blood donors (HBsAg negative). OBI was defined as the presence of HBV-DNA in at least two of four open reading frames (ORFs) of the HBV genome detected by nested PCR. SNPs in HLA-DPA1 (rs3077) and HLA-DPB1 (rs3135021, rs9277535, and rs2281388) were genotyped using real-time Taqman® genotyping assays.
Of 122 samples positive for anti-HBs and/or anti-HBc, 17 were determined as OBI. The minor allele in rs3077 was significantly correlated with OBI [odds ratio (OR) = 3.87, 95% confidence interval (CI) = 1.58-9.49, p = 0.0015]. The prevalence of the minor allele (T) was significantly higher in subjects with OBI than in those without (59% and 33%, respectively). The combination of haplotype markers (TGA for rs3077-rs3135021-rs9277535) was associated with increased risk of OBI (OR = 4.90, 95%CI = 1.12-21.52 p = 0.038). The prevalence of OBI was highest in the isolated anti-HBc group among the three seropositive categories: anti-HBs <500 mIU/ml, anti-HBs ≥500 mIU/ml, and isolated anti-HBc (29.41%, p = 0.014).
Genetic variants of HLA-DP and the presence of anti-HBc are important predictors of OBI in Indonesian blood donors.
Ref: KE/FK/194/EC; registered 01 March 2013. Continuing approval Ref: KE/FK/536/EC; registered 12 May 2014.
隐匿性乙型肝炎病毒感染（OBI）定义为乙型肝炎表面抗原（HBsAg）阴性个体血清和/或肝脏中存在乙型肝炎病毒（HBV）DNA。OBI与病毒传播风险相关，尤其是在发展中国家，并且与免疫抑制患者的进行性肝病和再激活相关。本研究的目的是评估 OBI 与 HLA-DP 单核苷酸多态性（SNP）之间的关系，这些 SNP 编码针对乙型肝炎病毒感染的免疫反应的抗原结合位点。由于 HLA-DP 变体影响 HBV 基因组的四个开放阅读框（ORF）中至少两个的 HBV-DNA 的 mRNA 表达，我们假设 HLA-DPA1 和 HLA-DPB1 的高表达水平有利于 OBI 的发展。
本研究纳入了 456 名印度尼西亚健康献血者（HBsAg 阴性）。OBI 定义为通过巢式 PCR 检测到 HBV 基因组的四个 ORF 中的至少两个中存在 HBV-DNA。使用实时 Taqman®基因分型测定法对 HLA-DPA1（rs3077）和 HLA-DPB1（rs3135021、rs9277535 和 rs2281388）中的 SNP 进行基因分型。
在 122 份抗-HBs 和/或抗-HBc 阳性的样本中，有 17 份被确定为 OBI。rs3077 的次要等位基因与 OBI 显著相关[比值比（OR）=3.87，95%置信区间（CI）=1.58-9.49，p=0.0015]。在 OBI 患者中，次要等位基因（T）的发生率明显高于无 OBI 患者（分别为 59%和 33%）。HLA-DP 单倍型标记物（rs3077-rs3135021-rs9277535 的 TGA）的组合与 OBI 的风险增加相关（OR=4.90，95%CI=1.12-21.52，p=0.038）。在三个血清阳性类别中的抗-HBc 阳性组中，OBI 的发生率最高：抗-HBs<500 mIU/ml、抗-HBs≥500 mIU/ml 和孤立性抗-HBc（29.41%，p=0.014）。
HLA-DP 的遗传变异和抗-HBc 的存在是印度尼西亚献血者 OBI 的重要预测因子。
Ref：KE/FK/194/EC；于 2013 年 3 月 1 日注册。持续批准 Ref：KE/FK/536/EC；于 2014 年 5 月 12 日注册。
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