Viral Hepatitis Research Laboratory, Institute of Infectious Diseases, Beijing, China.
J Med Virol. 2013 Oct;85(10):1698-704. doi: 10.1002/jmv.23640. Epub 2013 Jul 12.
This study investigated features and clinical implications of HBV mutations in patients with different clinical manifestations. In total, 516 patients were enrolled in this study, including 131 patients with acute hepatitis B, 239 patients with chronic hepatitis B, and 146 patients with acute-on-chronic liver failure. HBV genotypes and mutations were analyzed by direct sequencing of complete viral genomes. Genotypes B2, C1, C2, and D1 accounted for 22.2%, 1.6%, 74.6%, and 1.6%, respectively. Genotype B was more frequently detected in patients with acute hepatitis B than those with chronic hepatitis B and acute-on-chronic liver failure. Deletion mutations were detected mostly in preS1 and preS2 regions and the detection rates were 3.8%, 19.7%, and 24.7% for acute hepatitis B, chronic hepatitis B and acute-on-chronic liver failure patients, respectively. Incidences of point mutation T53C (preS1F53L), G1613A (polR841K), G1775A and A1762T + G1764A in the basal core promoter region, G1896A and G1899A in precore region and A2189C (coreI97L) in core region increased along with acute hepatitis B, chronic hepatitis B, and acute-on-chronic liver failure. The mutation G1896A was independently associated with poor survival of patients with acute-on-chronic liver failure. The gradual increase of viral mutation incidences was also observed in three HLA-A2-restricted cytotoxic T lymphocyte epitopes from HLA-A2-positive patients, that is env188-196 (5.8%, 10.1%, 22.5%), core107-115 (4.3%, 4.6%, 19.7%), and x92-100 (1.4%, 20.2%, 33.8%). In conclusion, certain viral mutations in various regions of HBV genome are associated with disease progression of HBV infection.
本研究旨在探讨不同临床表现患者乙型肝炎病毒（HBV）突变的特征及其临床意义。共纳入 516 例患者，其中急性乙型肝炎 131 例，慢性乙型肝炎 239 例，慢加急性肝衰竭 146 例。采用直接测序法分析 HBV 基因型和突变。基因型 B2、C1、C2 和 D1 分别占 22.2%、1.6%、74.6%和 1.6%。急性乙型肝炎患者中基因型 B 的检出率高于慢性乙型肝炎和慢加急性肝衰竭患者。缺失突变主要发生在 preS1 和 preS2 区，其检出率分别为急性乙型肝炎、慢性乙型肝炎和慢加急性肝衰竭患者的 3.8%、19.7%和 24.7%。在基础核心启动子区，点突变 T53C（preS1F53L）、G1613A（polR841K）、G1775A 和 A1762T+G1764A，在核心前区 G1896A 和 G1899A，以及核心区 A2189C（coreI97L）的发生率随着急性乙型肝炎、慢性乙型肝炎和慢加急性肝衰竭的进展而增加。G1896A 突变与慢加急性肝衰竭患者的不良预后独立相关。在 HLA-A2 阳性患者的三个 HLA-A2 限制性细胞毒性 T 淋巴细胞表位中，也观察到病毒突变发生率的逐渐增加，即 env188-196（5.8%、10.1%、22.5%）、core107-115（4.3%、4.6%、19.7%）和 x92-100（1.4%、20.2%、33.8%）。总之，HBV 基因组不同区域的某些病毒突变与 HBV 感染的疾病进展有关。
