Li Xinyan, Li Fahong, Zhang Yao, Kang Yaoyue, Yu Jie, Yang Feifei, Liu Hongyan, Qin Yanli, Huang Yuxian, Mao Richeng, Zhang Jiming
Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China; Department of Hepatitis Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
Biochem Biophys Res Commun. 2015 Sep 4;464(4):1185-1191. doi: 10.1016/j.bbrc.2015.07.101. Epub 2015 Jul 23.
Some patients with chronic hepatitis B (CHB) receiving entecavir (ETV) exhibit partial virological response (PVR) to ETV and the mechanism is not clear. In this study, we aim to investigate the in vitro susceptibility of residual clinical strains isolated from the sera of nucleos(t)ide-naïve hepatitis B virus e antigen (HBeAg)-positive patients with CHB and PVR to ETV, and to evaluate the clinical and virological responses to prolonged ETV monotherapy in these patients. We followed 69 nucleos(t)ide-naïve HBeAg-positive CHB patients receiving ETV treatment, with 13 partial responders to ETV. And we found that no genotypic resistance mutants were detected among the 13 PVR patients. Phenotypic analysis revealed that the residual HBV strains had normal replication capacity, and were as susceptible to ETV as wild-type HBV. All PVR patients continued to receive ETV monotherapy, and serum HBV DNA of the majority became undetectable after prolonged treatment. However, none of these patients achieved HBeAg loss. In contrast, 25.6% and 23.2% of the patients with virological response achieved HBeAg loss (P < 0.001) and HBeAg seroconversion (P < 0.001) at week 144, respectively. Thus, we conclude suboptimal response to ETV might not be due to reduced HBV susceptibility to ETV, and prolonging ETV monotherapy in patients with PVR is recommended.
一些接受恩替卡韦（ETV）治疗的慢性乙型肝炎（CHB）患者对ETV表现出部分病毒学应答（PVR），其机制尚不清楚。在本研究中，我们旨在调查从初治的乙型肝炎病毒e抗原（HBeAg）阳性CHB且有PVR的患者血清中分离出的残留临床毒株对ETV的体外敏感性，并评估这些患者延长ETV单药治疗后的临床和病毒学应答。我们随访了69例接受ETV治疗的初治HBeAg阳性CHB患者，其中13例为ETV部分应答者。我们发现，在这13例PVR患者中未检测到基因型耐药突变体。表型分析显示，残留的HBV毒株具有正常的复制能力，对ETV的敏感性与野生型HBV相同。所有PVR患者继续接受ETV单药治疗，延长治疗后大多数患者的血清HBV DNA检测不到。然而，这些患者均未实现HBeAg消失。相比之下，病毒学应答患者在第144周时分别有25.6%和23.2%实现了HBeAg消失（P<0.001）和HBeAg血清学转换（P<0.001）。因此，我们得出结论，对ETV反应欠佳可能并非由于HBV对ETV的敏感性降低，建议对PVR患者延长ETV单药治疗。
