AASLD 2013恩替治疗基线和治疗血清HBsAg定量水平预测价值

StephenW

TITLE: Predictive Value of Baseline and On-Treatment Quantitative Serum HBsAg Levels in Therapeutic Outcome to Entecavir in Patients with Chronic Hepatitis B

AUTHORS (FIRST NAME, LAST NAME): Cheng-Yuan Peng1, Hsueh-Chou Lai1, Wen- Pang Su1, Chia-Hsin Lin1, Po-Heng Chuang1, Sheng-Hung Chen1
Institutional Author(s):
INSTITUTIONS (ALL): 1. Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
ABSTRACT BODY: Background: The predictive value of baseline and on-treatment quantitative serum hepatitis B surface antigen (qHBsAg) levels in the therapeutic outcome to entecavir (ETV) in chronic hepatitis B (CHB) patients remains unclear. Patients and Methods: Between June 2006 and May 2013, 321 treatment-naïve compensated CHB patients had been treated with ETV for at least 1 year. Serum HBsAg and HBV DNA levels were quantified using the Abbott Architect HBsAg QT assay and the Cobas Amplicor HBV Monitor Test during therapy, respectively. Results: The baseline features were: median age: 49 years, 75.1% men, 37.4% HBeAg-positive (N=120), 59.1% genotype B infection, median ALT: 79 IU/L, HBV DNA: 6.56 log10copies/mL, and qHBsAg: 3.29 log10IU/mL. Among them, 218, 163 and 81 patients have received ETV therapy for ≧3, 4 and 5 years, respectively, with the mean treatment duration of 45.8 ± 18.3 months. The cumulative rates for virological response (VR, HBV DNA <312 copies/mL) were 90.3%, 97.8% and 99.4% at 1, 2 and 3 years, respectively. The cumulative HBeAg loss rates were 12.5%, 32.9%, 50%, 59% and 77.4% at 1, 2, 3, 4 and 5 years, respectively. Multivariate logistic regression analyses identified baseline HBV DNA <8 log10 copies/mL(OR=5.746, P=0.0044) and qHBsAg decline from baseline ≧50% at 3 months of therapy (OR=4.202, P=0.0207) as predictors of VR at one year for the HBeAg-positive subgroup. Multivariate Cox regression analyses identified ALT ≧120 IU/L (HR=1.881, P=0.0369) and baseline qHBsAg level between 5000 to 16000 IU/mL (HR=4.421, P=0.0008) as predictors of HBeAg loss during treatment. The cumulative HBeAg loss rates after 5 years of therapy in patients with baseline qHBsAg ≧16000, 5000-16000, and <5000 IU/mL were 50%, 100%, and 77.8%, respectively (P=0.005). Multivariate Cox regression analyses showed that baseline qHBsAg level <3.5 log10 IU/mL (HR=4.784, P=0.021) and qHBsAg decline from baseline ≧50% at 3 months of therapy (HR=4.115, P=0.0368) were predictors of achieving qHBsAg level ≦2 log10IU/mL during treatment in HBeAg-positive patients, and that baseline qHBsAg level <2.5 log10 IU/mL (HR=3.965, P=0.0059) and qHBsAg decline from baseline ≧50% at 12 months of therapy (HR=22.355, P<0.0001) were predictors of achieving qHBsAg level ≦2 log10IU/mL during treatment in HBeAg-negative patients. Conclusion: Baseline qHBsAg and ALT levels are predictors of HBeAg loss during ETV therapy in HBeAg-positive patients. Baseline qHBsAg levels and on-treatment qHBsAg decline from baseline are predictors of achieving qHBsAg level ≦2 log10IU/mL during ETV therapy in both HBeAg-positive and -negative patients.

StephenW

背景：基线和治疗的定量血清乙肝表面抗原水平（ qHBsAg ） ，恩替卡韦（ ETV ）在慢性乙型肝炎（ CHB ）患者的治疗结果的预测值仍不清楚。病人与方法： 2006年6月至2013年5月321治疗初治CHB患者补偿已恩替卡韦治疗至少1年。血清HBsAg和HBV DNA水平进行定量分别在治疗过程中，使用雅培Architect HBsAg的QT检测和COBAS AMPLICOR HBV显示器测试。结果：基线特征为：平均年龄：49岁，男性占75.1 ％ ， 37.4 ％， HBeAg阳性（ N = 120 ） ， 59.1％感染B基因型， ALT中位数：79 IU / L， HBV-DNA ：6.56 log10copies/mL qHBsAg ： 3.29 log10IU/mL 。其中， 218 ， 163和81例患者接受ETV治疗≧3年， 4年和5年，分别为45.8 ±18.3个月的平均治疗时间。累计病毒学应答率（ VR ， HBV DNA < 312拷贝/ ml ）分别为90.3 ％ ，97.8 ％和99.4 ％ ，分别在1年， 2年和3年。累积HBeAg转阴率分别为12.5％ ，32.9％ ， 50 ％ ， 59％和77.4 ％，在1 ， 2， 3 ， 4年和5年，分别。多因素Logistic回归分析确定基线HBV DNA < 8个log10拷贝/毫升（ OR = 5.746 ，P = 0.0044 ）和qHBsAg下降，从基线≧50 ％，治疗3个月（ OR = 4.202 ，P = 0.0207 ）作为预测的VR HBeAg阳性亚组为一年。多元回归分析确定ALT ≧ 120 IU / L （ HR = 1.881 ，P = 0.0369 ）和基线qHBsAg的水平介于5000至16000国际单位/毫升（ HR = 4.421 ，P = 0.0008 ） ，在治疗过程中HBeAg消失的预测。经过5年的治疗中患者基线qHBsAg累积HBeAg转阴率≧ 16000 ， 5000-16000 ，和< 5000 IU / mL的分别为50 ％， 100％， 77.8 ％ ，分别为（P = 0.005 ） 。多元回归分析表明，的基线qHBsAg水平< 3.5个log10 IU /毫升（ HR = 4.784 ， P = 0.021 ） ，从基线qHBsAg下降≧50 ％在治疗3个月（ HR = 4.115 ，P = 0.0368 ）预测实现qHBsAg水平≦ 2 log10IU/mL在HBeAg阳性患者在治疗过程中，的基线qHBsAg水平< 2.5个log10 IU /毫升（ HR = 3.965 ，P = 0.0059 ）和12个月的治疗，从基线下降≥ 50 ％ qHBsAg （ HR = 22.355 ，P <0.0001 ）的预测实现qHBsAg级≦ 2 log10IU/mL HBeAg阴性患者治疗期间。结论：的基线qHBsAg和ALT水平是预测在ETV治疗HBeAg阳性患者HBeAg消失。基线qHBsAg水平和治疗qHBsAg的下降，从基线预测实现qHBsAg水平≦ 2 log10IU/mL ;在ETV治疗HBeAg阳性和阴性患者。