Fujian Clinical Research Center for Laboratory Medicine of Immunology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Department of Laboratory Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China; Department of Laboratory Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China; Gene Diagnostic Research Center, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Int J Med Microbiol. 2024 Jun;315:151619. doi: 10.1016/j.ijmm.2024.151619. Epub 2024 Mar 27.
To analysis of quasispecies (QS) changes and high-frequency mutations in the BCP/PreC/C region of patients at different phases of hepatitis B virus (HBV) infection and provides novel biomarkers for the diagnosis of chronic hepatitis B (CHB) patients.
With the application of next-generation sequencing technology, we were able to sequence the HBV BCP/PreC/C regions in 40 patients, each at different phases of the HBV infection. The heterogeneity of QS and the frequency of mutations were calculated using MEGA 7 software.
Our results show that the complexity and diversity of the BCP/PreC/C QS in HBeAg-positive CHB patients are significantly higher than those in HBeAg-positive chronic infection patients, while HBeAg-negative chronic infection patients had significantly higher QS complexity and diversity than HBeAg-negative CHB patients. In addition, HBeAg-negative patients showed reduced complexity but increased diversity compared with HBeAg-positive patients. Receiver operating characteristic curves showed that G1764A, C2102T, dN and complexity of QS could be used as potential biomarkers for diagnosing HBeAg-positive CHB, while the A2189C, dS and complexity of QS could be used as potential biomarkers for diagnosing HBeAg-negative chronic hepatitis. Finally, our study also found that G1896A and A2159G may be hotspot mutations affecting HBeAg seroconversion.
Our research elucidates the evolution of HBV by analyzing QS heterogeneity and mutation patterns, offering novel serum biomarkers for enhancing clinical diagnosis and disease prognosis. This comprehensive approach sheds light on the intricate dynamics of HBV progression and paves the way for more precise medical interventions.
分析乙型肝炎病毒(HBV)感染不同阶段患者 BCP/PreC/C 区准种(QS)变化和高频突变,为慢性乙型肝炎(CHB)患者的诊断提供新的生物标志物。
应用下一代测序技术,对 40 例不同 HBV 感染阶段的患者的 HBV BCP/PreC/C 区进行测序。使用 MEGA 7 软件计算 QS 的异质性和突变频率。
结果显示,HBeAg 阳性 CHB 患者的 BCP/PreC/C QS 的复杂性和多样性明显高于 HBeAg 阳性慢性感染患者,而 HBeAg 阴性慢性感染患者的 QS 复杂性和多样性明显高于 HBeAg 阴性 CHB 患者。此外,与 HBeAg 阳性患者相比,HBeAg 阴性患者的复杂性降低而多样性增加。受试者工作特征曲线显示,G1764A、C2102T、dN 和 QS 复杂性可作为诊断 HBeAg 阳性 CHB 的潜在生物标志物,而 A2189C、dS 和 QS 复杂性可作为诊断 HBeAg 阴性慢性肝炎的潜在生物标志物。最后,我们的研究还发现 G1896A 和 A2159G 可能是影响 HBeAg 血清学转换的热点突变。
通过分析 QS 异质性和突变模式,阐明了 HBV 的进化,为增强临床诊断和疾病预后提供了新的血清生物标志物。这种综合方法揭示了 HBV 进展的复杂动态,为更精确的医学干预铺平了道路。