Ribeiro Ruy M, Germanidis Georgios, Powers Kimberly A, Pellegrin Bertrand, Nikolaidis Paul, Perelson Alan S, Pawlotsky Jean-Michel
Los Alamos National Laboratory, Los Alamos, New Mexico, USA.
J Infect Dis. 2010 Nov 1;202(9):1309-18. doi: 10.1086/656528.
Hepatitis B e antigen (HBeAg)–negative chronic hepatitis B infection has a presentation and clinical course that is divergent from that of HBeAg‐positive infection. The former usually presents with lower viral levels but faster progression to liver disease. We sought to better understand the balance between replication and the immune response against hepatitis B virus (HBV).
Viral kinetics in 50 HBeAg‐negative patients under various treatment protocols with interferon α and/or nucleoside or nucleotide analogs was analyzed. HBV DNA level was measured frequently and the data fitted to a viral dynamic model. A meta‐analysis of all published studies of viral kinetics in HBeAg‐positive and HBeAg‐negative infection was also conducted.
We found that the clearance of both HBV virions and infected cells was significantly faster in HBeAg‐negative infection than in HBeAg‐positive infection. In HBeAg‐negative infection, there was also a negative correlation between baseline HBV DNA levels and infected cell half‐life, suggesting that the higher the viral load the faster the turnover of infected cells.
These results reveal the dual role played by the immune response in maintaining lower viral levels and inducing faster turnover of infected cells, the latter of which may be responsible for the more aggressive nature of HBeAg‐negative infection.
乙肝e抗原（HBeAg）阴性的慢性乙型肝炎感染的表现和临床病程与HBeAg阳性感染不同。前者通常病毒水平较低，但肝病进展较快。我们试图更好地理解乙肝病毒（HBV）复制与免疫反应之间的平衡。
分析了50例HBeAg阴性患者在使用干扰素α和/或核苷或核苷酸类似物的各种治疗方案下的病毒动力学。频繁测量HBV DNA水平，并将数据拟合到病毒动力学模型。还对所有已发表的关于HBeAg阳性和HBeAg阴性感染的病毒动力学研究进行了荟萃分析。
我们发现，HBeAg阴性感染中HBV病毒颗粒和受感染细胞的清除明显快于HBeAg阳性感染。在HBeAg阴性感染中，基线HBV DNA水平与受感染细胞半衰期之间也存在负相关，这表明病毒载量越高，受感染细胞的更新速度越快。
这些结果揭示了免疫反应在维持较低病毒水平和诱导受感染细胞更快更新方面所起的双重作用，后者可能是HBeAg阴性感染更具侵袭性的原因。
