Choi Han Na, Song Jeong Eun, Lee Hyeon Chul, Jo Hyeong Ho, Lee Chang Hyeong, Kim Byung Seok
Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, Korea.
Clin Mol Hepatol. 2015 Mar;21(1):24-31. doi: 10.3350/cmh.2015.21.1.24. Epub 2015 Mar 25.
BACKGROUND/AIMS: The optimal management of patients exhibiting a partial virologic response (PVR) to entecavir (ETV) has not been determined. The aim of this study was to determine the long-term efficacy of prolonged ETV monotherapy in treatment-naïve chronic hepatitis B (CHB) patients exhibiting a PVR to ETV therapy.
This study included 364 treatment-naïve CHB patients treated with ETV for ≥48 weeks and who received continuous ETV monotherapy for ≥96 weeks. PVR was defined as a decrease in serum hepatitis B virus (HBV) DNA of more than 2 log(10) IU/mL from baseline but with detectable HBV DNA by real-time PCR assay at week 48.
Fifty-two of the 364 patients (14.3%) showed a PVR. Among them, 41 patients received continuous ETV monotherapy for ≥96 weeks (median duration 144 weeks, range 96-312 weeks), and 40 of these patients (95%) achieved a virologic response (VR, HBV DNA <20 IU/mL) during prolonged ETV monotherapy (median duration 78 weeks, range 60-288 weeks). The cumulative probabilities of a VR at weeks 96, 144, and 192 from treatment initiation were 78.0%, 92.7%, and 95.1%, respectively. The VR rate was 97.2% (35/36) in HBeAg-positive patients and 100% (5/5) in HBeAg-negative patients. In multivariate analysis, HBeAg positivity (odds ratio [OR], 9.231; 95% confidence interval [CI], 1.03-82.91; P=0.047) and a high baseline HBV DNA level (OR, 0.170; 95% CI, 0.08-0.37; P=0.000) were independently associated with a delayed virologic response. No patient developed genotypic resistance to ETV during follow-up.
Long-term ETV monotherapy is effective for achieving a VR in treatment-naïve CHB patients exhibiting a PVR to ETV. HBeAg positivity and high baseline HBV DNA level were independently associated with a delayed virologic response.
背景/目的：对于对恩替卡韦（ETV）出现部分病毒学应答（PVR）的患者，最佳治疗方案尚未确定。本研究的目的是确定在初治慢性乙型肝炎（CHB）患者中，延长ETV单药治疗对ETV治疗出现PVR患者的长期疗效。
本研究纳入了364例初治CHB患者，这些患者接受ETV治疗≥48周，并持续接受ETV单药治疗≥96周。PVR定义为血清乙型肝炎病毒（HBV）DNA较基线水平下降超过2 log(10) IU/mL，但在第48周通过实时PCR检测仍可检测到HBV DNA。
364例患者中有52例（14.3%）出现PVR。其中，41例患者持续接受ETV单药治疗≥96周（中位疗程144周，范围96 - 312周），这些患者中有40例（95%）在延长的ETV单药治疗期间（中位疗程78周，范围60 - 288周）实现了病毒学应答（VR，HBV DNA <20 IU/mL）。从治疗开始第96、144和192周时VR的累积概率分别为78.0%、92.7%和95.1%。HBeAg阳性患者的VR率为97.2%（35/36），HBeAg阴性患者的VR率为100%（5/5）。多因素分析显示，HBeAg阳性（比值比[OR]，9.231；95%置信区间[CI]，1.03 - 82.91；P = 0.047）和高基线HBV DNA水平（OR，0.170；95% CI，0.08 - 0.37；P = 0.000）与病毒学应答延迟独立相关。随访期间无患者出现对ETV的基因型耐药。
长期ETV单药治疗对于在初治CHB患者中对ETV出现PVR的患者实现VR是有效的。HBeAg阳性和高基线HBV DNA水平与病毒学应答延迟独立相关。
