Molecular characterization of hepatitis B virus (HBV) in African children living in Australia identifies genotypes and variants associated with poor clinical outcome
Molecular characterization of hepatitis B virus (HBV) in African children living in Australia identifies genotypes and variants associated with poor clinical outcome
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DOI：
10.1099/jgv.0.001086
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发表时间：
2018-08-01
影响因子：
3.8
通讯作者：
Revill, Peter A.
中科院分区：
文献类型：
--
作者：
Bannister, Elizabeth G.;Yuen, Lilly;Revill, Peter A.
来自撒哈拉以南非洲的移民导致澳大利亚慢性乙型肝炎 (CHB) 感染及其并发症的发病率不断上升。非洲 CHB 与独特的基因型相关，例如 E 和 A1，它们分别与疫苗功效降低和早发性肝细胞癌相关，尽管非洲以外这些基因型的流行情况知之甚少。墨尔本皇家儿童医院招募了未经治疗的非洲裔慢性乙型肝炎儿童。对完整 HBV 基因组或临床相关的基础核心启动子 (BCP)/前核心 (PC) 区域进行基于群体的测序，并通过系统发育分析分配 HBV 基因型/亚基因型。对 67 名儿童（中位年龄 12.5 岁）的血清进行了 HBV 特征分析。 HBV 基因型 E 最常见 (70%)，基因型 D [25%；亚基因型 D6（以前称为 D7）/D3/D2）] 和亚基因型 A1（5%）也已被鉴定。尽管年龄很小，但超过 50% 的儿童 HBeAg 阴性，并且血清转化为抗 HBe，这在大多数情况下与典型的 BCP/PC 突变有关。居住在澳大利亚的非洲儿童的 HBV 特征是早期 HBeAg 血清转化和与不良临床结果相关的 HBV 变异感染，以及先前与疫苗功效降低或快速进展为肝癌相关的基因型。这些发现对澳大利亚儿科环境中的患者监测和治疗指南具有重要影响。
Migration from sub-Saharan Africa is contributing to the rising incidence of chronic hepatitis B (CHB) infection and its complications in Australia. African CHB is associated with unique genotypes, such as E and A1, which are associated with reduced vaccine efficacy and early-onset hepatocellular carcinoma, respectively, although the prevalence of these genotypes outside Africa is poorly described. Treatment-naive children of African origin with CHB were recruited at the Royal Children's Hospital Melbourne. Population-based sequencing of the complete HBV genome, or the clinically relevant basal core promoter (BCP)/precore (PC) region, was performed, and the HBV genotype/subgenotype assigned by phylogenetic analysis. HBV was characterized in serum from 67 children, median age 12.5 years. HBV genotype E was most frequent (70 %), with genotype D [25 %; subgenotypes D6 (formerly D7)/D3/D2)] and subgenotype A1 (5 %) also being identified. Despite their young age, over 50 % of the children were HBeAg-negative and had seroconverted to anti-HBe, with this being associated with canonical BCP/PC mutations in the majority of cases. The profile of HBV in African children living in Australia was characterized by early HBeAg seroconversion and infection with HBV variants associated with poor clinical outcome, as well as genotypes previously associated with reduced vaccine efficacy or rapid progression to liver cancer. These findings have important ramifications for patient monitoring and treatment guidelines in the Australian paediatric setting.