EASL 2013:恩替卡韦治疗5年期间,血清乙肝表面抗原水平

StephenW

Abstract 772
   
SERUM HEPATITIS B SURFACE ANTIGEN LEVELS DURING FIVE YEARS ENTECAVIR THERAPY IN ASIAN CHRONIC HEPATITIS B PATIENTS   
     
W.-K. Seto*, Y.-F. Lam, J. Fung, D.K.-H. Wong, C.-L. Lai, M.-F. Yuen
Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong S.A.R.. *[email protected]

Background: Change in hepatitis B surface antigen (HBsAg) levels during long-term nucleoside analogue therapy in chronic hepatitis B (CHB) has not been well investigated.
Aim: To determine the serologic, biochemical, virologic responses and resistance profile of continuous entecavir up to 5 years.
Methods: 222 (70.7% male, median age 45 years) CHB patients started on entecavir between July 2005 and November 2007 were recruited. The rates of HBV DNA detectability, hepatitis B e antigen (HBeAg) seroconversion, alanine aminotransferase (ALT) normalization, and entecavir signature mutations up to year 5 were determined. Serum HBV DNA and HBsAg levels were measured by Cobas Taqman and Elecsys II assay respectively. Resistance profile was determined by a line probe assay (LiPA) for patients with detectable HBV DNA.
Results: 222, 188, 173, 170 and 156 patients were followed up for 1, 2, 3, 4 and 5 years respectively. The rates of HBV DNA undetectability, HBeAg seroconversion for HBeAg-positive patients and ALT normalization (for patients with elevated baseline ALT) at year 5 were 97.4%, 55.7% and 91.4% respectively. 1 patient developed HBsAg seroclearance at year 2. 2 patients developed entecavir signature mutations at years 3 and 5 (rt180M, rt204V, rt184S/C/G/A and rt180M, rt204V, rt184I/L/F/M, rt202G, rt250V respectively), resulting in a cumulative resistance of 1.2% up to year 5. Among patients with 5 years of follow-up (n=156), the median annual HBsAg decline was 0.116 (range -0.176 to 0.980) log IU/mL/year with HBeAg-positive patients having a greater median HBsAg decline when compared to HBeAg-negative patients (0.141 and 0.097 log IU/mL/year respectively, p=0.021). Patients with significant HBsAg decline, defined as >0.25 log IU/mL/year (n=31), when compared to patients without significant HBsAg decline, was associated with younger median age (43.5 and 49.3 years respectively, p=0.014), HBeAg-positivity (54.8% and 34.7% respectively, p=0.039), and higher median baseline HBV DNA levels (7.99 and 6.22 log IU/mL respectively, p< 0.001).
Conclusion: Entecavir for 5 years achieved excellent rates of virologic suppression and low rates of resistance. Serum HBsAg levels decreased gradually during treatment, with a higher rate of decline seen in younger HBeAg-positive patients.
Acknowledgement: This study was supported by an unrestricted grant from Bristol-Myers Squibb.


Assigned speakers:
Dr. Wai-Kay Seto, The University of Hong Kong, Queen Mary Hospital , Hong Kong , Hong Kong S.A.R.

Assigned in sessions:
26.04.2013, 09:00-18:00, Poster Session, P02-07c, Category 07c: Viral Hepatitis B & D: Clinical (therapy, new compounds, resistance), Poster Area

StephenW

背景：乙肝表面抗原（HBsAg）水平在长期的核苷类似物治疗慢性乙型肝炎（CHB）的变动一直没有得到很好的调查。
目的：确定血清学，生物化学，病毒学反应和电阻档连续长达5年的恩替卡韦。
方法：222（70.7％为男性，平均年龄45岁）慢性乙肝患者，恩替卡韦在2005年7月和2007年11月开始招募。 HBV DNA可探测，乙肝e抗原（HBeAg）血清学转换，谷丙转氨酶（ALT）正常化，以及高达5年的恩替卡韦签名突变率进行测定。科瓦斯TaqMan和ELECSYS的II分别检测血清HBV DNA和HBsAg水平测定。电阻档被确定为患者检测到HBV DNA探针检测线（LIPA）。
分别为1，2，3，4，5年随访结果：222，188，173，170和156例。 HBV DNA不可检测率，HBeAg血清转换的HBeAg阳性患者和ALT正常化（患者基线ALT升高）在5年分别为97.4％，55.7％和91.4％。第2年，1例患者出现乙肝表面抗原转阴。 2例3年和5（rt180M，rt204V，rt184S/C/G/A rt180M rt204V rt184I/L/F/M rt202G，分别rt250V），恩替卡韦签名突变造成的累积阻力为1.2％长达5年。在5年的随访组（n = 156）的患者，平均年薪为乙肝表面抗原下降为0.116（-0.176 0.980）日志IU /毫升/年的HBeAg阳性患者具有更大的HBsAg下降中位数相比大三阳阴性的患者（0.141和0.097日志IU /毫升/年，P = 0.021）。患者具有显着的HBsAg下降，定义为> 0.25日志IU /毫升/年组（n = 31）相比，当患者没有明显的HBsAg下降，是与年轻的年龄中位数（分别为43.5和49.3岁，P = 0.014），HBeAg的阳性（分别为54.8％和34.7％，P = 0.039）和较高的平均基线HBV DNA水平（7.99和6.22日志IU /毫升，P <0.001）。
结论：5年取得了优异的恩替卡韦的病毒学抑制率和低的电阻率。血清HBsAg水平逐渐下降，在治疗过程中，看到年轻的HBeAg阳性患者具有较高的下降率。
鸣谢：这项研究是由百时美施贵宝公司不受限制的资金支持。