AASLD2016[1847扰素联合治疗后高HBsAg损失率5年随访结果

StephenW

1847
High Rate of HBsAg Loss After Peginterferon Based
Combination Treatment for Chronic Hepatitis B Patients:
Results After 5 Years of Follow-up
Femke Stelma1, Meike H. van der Ree1, Martine W. Peters1, Louis
Jansen1, Annikki de Niet1, Harry L. Janssen2,3, Hans L. Zaaijer4, R
B. Takkenberg4, Hendrik W. Reesink4; 1Department of Gastroenterology
and Hepatology, Academic Medical Center, Amsterdam,
Netherlands; 2Department of Gastroenterology and Hepatology,
Erasmus Medical Centre, Amsterdam, Netherlands; 3Toronto Centre
for Liver Disease, Toronto Western & General Hospital, University
Health Network, Toronto, ON, Canada; 4Department of
Virology, Academic Medical Center, Amsterdam, Netherlands

Background and aims Combining peginterferon alfa-2a
(pegIFN) with a nucleotide analogue can result in higher rates
of HBsAg loss than either therapy given alone. However, the
long term sustainability of HBsAg loss upon such treatment
regimens is not well known. In this study we investigated the
5-year outcome in chronic hepatitis B (CHB) patients treated
with pegIFN and adefovir combination therapy. Methods In
the initial study, 92 CHB patients were included. At baseline,
patients (44 HBeAg positive, 48 HBeAg negative) had HBV
DNA levels > 100,000 c/mL (17,182 IU/mL) and elevated
ALT levels or histological signs of active hepatitis. Patients were
treated for 48 weeks with pegIFN alfa-2a 180 mcg/week and
10 mg adefovir dipivoxil daily. During long term follow-up, routine
check-up and laboratory testing was performed yearly. At
year 5 of follow-up 70 (32 HBeAg positive, 38 HBeAg negative)
patients were still included. Results At year 5, 19% (6/32)
of HBeAg positive patients and 16% (6/38) of HBeAg negative
patients had HBsAg loss, no sero-reversion was observed.
The 5-year cumulative Kaplan-Meier estimate for HBsAg loss
was 17.2% for HBeAg positive patients and 19.3% for HBeAg
negative patients (Figure). Of the 16 patients who lost HBsAg,
12 patients reached end of follow-up; 2 died and 2 were lost
to follow up. 14/16 patients who lost HBsAg had positive anti-
HBs antibodies (>10 IU/L). At the end of 5 years follow-up,
2/32 HBeAg positive patients and 5/38 HBeAg negative
patients had a durable combined response (HBV DNA <2,000
IU/mL with ALT normalization and HBeAg negativity excluding
retreated patients and patients with HBsAg loss). The cumulative
Kaplan-Meier estimate for retreatment was 60% of patients
at year 5. Conclusion At year 5 of follow-up, 17-19% of CHB
patients treated with pegIFN based combination therapy had
HBsAg loss and 88% of these had developed anti-HBs antibodies.
PegIFN based combination treatment can lead to a durable
functional cure in patients with chronic hepatitis B.

StephenW

AASLD2016 [1847扰素联合治疗后高HBsAg损失率5年随访结果
聚乙二醇干扰素后高HBsAg损失率高
慢性乙型肝炎患者的联合治疗：
5年随访结果
Femke Stelma1，Meike H.van der Ree1，Martine W. Peters1，Louis
Jansen1，Annikki de Niet1，Harry L.Janssen2,3，Hans L.Zaaijer4，R
B. Takkenberg4，Hendrik W. Reesink4;消化内科
和Hepatology，Academic Medical Center，Amsterdam，
荷兰; 2胃肠病与肝病，
Erasmus医疗中心，荷兰阿姆斯特丹; 3多伦多中心
为肝病，多伦多西部和总医院，大学
健康网络，多伦多，ON，加拿大; 4
Virology，Academic Medical Center，Amsterdam，Netherlands

背景和目的组合聚乙二醇干扰素α-2a
（pegIFN）与核苷酸类似物可导致更高的速率
的HBsAg损失比任何单独治疗。但是，
这种治疗后HBsAg损失的长期可持续性
方案不是众所周知的。在这项研究中我们调查了
治疗的慢性乙型肝炎（CHB）患者的5年结果
与pegIFN和阿德福韦联合治疗。方法
初步研究，包括92例CHB患者。在基线，
患者（44 HBeAg阳性，48 HBeAg阴性）有HBV
DNA水平> 100,000 c / mL（17,182 IU / mL）并升高
ALT水平或活动性肝炎的组织学体征。病人是
用pegIFNα-2a 180mcg /周治疗48周
每日10毫克阿德福韦酯。在长期随访期间，常规
每年进行检查和实验室测试。在
第5年随访70（32 HBeAg阳性，38 HBeAg阴性）
患者仍包括在内。结果在第5年，19％（6/32）
的HBeAg阳性患者和16％（6/38）的HBeAg阴性
患者出现HBsAg缺失，未观察到血清阳转。
HBsAg损失的5年累积Kaplan-Meier估计
HBeAg阳性患者为17.2％，HBeAg为19.3％
阴性患者（图）。在16例失去HBsAg的患者中，
12例患者达到随访结束; 2人死亡，2人失踪
去跟随。 14/16例失去HBsAg的患者，
HBs抗体（> 10IU / L）。在5年随访结束时，
2/32 HBeAg阳性患者和5/38 HBeAg阴性
患者具有持久的联合应答（HBV DNA <2,000
IU / mL，ALT标准化和HBeAg阴性排除
退出的患者和HBsAg消失的患者）。累积
Kaplan-Meier评估的再治疗是60％的患者
。结论在随访的5年，CHB的17-19％
基于pegIFN的联合治疗患者
HBsAg消失，其中88％发展为抗HBs抗体。
基于PegIFN的组合治疗可以导致耐久性
功能性治愈慢性乙型肝炎患者。