Precore and Basal Core Promoter Hepatitis B Virus (HBV) Variants Are Present From a Young Age and Differ Across HBV Genotypes.
Precore and Basal Core Promoter Hepatitis B Virus (HBV) Variants Are Present From a Young Age and Differ Across HBV Genotypes.
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DOI：
10.1002/hep.31506
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发表时间：
2021-05
期刊：
影响因子：
--
通讯作者：
Hepatitis B Research Network
中科院分区：
文献类型：
--
作者：
Lau DTY;Ganova-Raeva L;Wang J;Mogul D;Chung RT;Lisker-Melman M;Chang KM;Shaikh OS;Janssen HLA;Wahed AS;Lok AS;Hepatitis B Research Network
B型肝炎病毒（HBV）前C区（PC）和双基底核心启动子（BCP）突变分别停止和下调B e抗原（HBeAg）的产生。HBV基因型A与PC突变很少相关。我们试图在北美不同种族的人群中研究这些变异与HBV基因型、年龄和HBeAg状态的关系。前瞻性研究包括B型肝炎研究网络的1,036名参与者（808名成人，228名儿童）。通过桑格测序确定PC和BCP变体，并报告了优势HBV种类（>50%）。中位年龄为36.3岁（范围，2-80岁），44.6% HBeAg（+），74.2%亚洲人，13.3%黑人和9.7%白色人。29.4%的受试者存在显性PC变异，包括20例A1或A2亚型。20例基因型A和PC的参与者中有17例有补偿性C1858 T突变。在HBeAg（+）队列中，PC和/或BCP变异的患病率从前20年的14.4%增加到40岁后的51%。在2-18岁的人群中，52%和83%的PC和BCP显性变异体为HBeAg（+），而在>40岁的人群中为3.8%和29%。携带显性PC或BCP变异的患者HBeAg清除率显著高于野生型HBV患者：24.4和15.0/100人-年，而野生型HBV患者为6.0/100人-年（P < 0.0001）。PC变异体可以存在于HBV基因型A中，并且通常与C1858 T相关，其保留了前基因组重排序列。PC和BCP变异体的选择发生在年轻时，各年龄组的患病率不断增加。具有主导PC和BCP变体的HBeAg（+）参与者进入慢性HBV感染的HBeAg（-）阶段的速度明显更快。这一发现具有潜在的临床和治疗意义。
Hepatitis B virus (HBV) precore (PC) and dual basal core promoter (BCP) mutations halt and down-regulate hepatitis B e antigen (HBeAg) production respectively. PC mutation is rarely associated with HBV genotype A. We sought to examine the association of these variants with HBV genotypes, age, and HBeAg status in a racially diverse population in North America. Prospective study included 1,036 (808 adults, 228 children) participants in the Hepatitis B Research Network. PC and BCP variants were determined by Sanger sequencing, and dominant HBV species (>50%) were reported. Median age was 36.3 years (range, 2–80), 44.6% HBeAg(+), 74.2% Asians, 13.3% black, and 9.7% white. The dominant PC variant was present in 29.4% participants, including 20 with subgenotype A1 or A2. Seventeen of 20 participants with genotype A and PC had a compensatory C1858T mutation. In the HBeAg(+) cohort, the prevalence of PC and/or BCP variants increased from 14.4% in the first two decades to 51% after 40 years of age. Among those aged 2–18, 52% and 83% with dominant PC and BCP variants were HBeAg(+) compared to 3.8% and 29% in the >40 years age group. HBeAg clearance rates were significantly higher for those with dominant PC or BCP variants: 24.4 and 15.0 per 100 person-years compared to 6.0 in wild-type HBV (P < 0.0001). PC variants can be present in HBV genotype A and are usually associated with C1858T, which preserves the pregenome encapsidation sequence. Selection of PC and BCP variants occurred at a young age, with increasing prevalence across age groups. HBeAg(+) participants with dominant PC and BCP variants progressed to the HBeAg(−) phase of chronic HBV infection significantly faster. This finding has potential clinical and therapeutic implications.
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