EASL2019 PS-056 起病的患者复发率和再治疗率较高 停止长期核后

StephenW

PS-056
Higher relapse and retreatment rates in patients who started as
HBeAg positive than negative after stopping long-term nucleos (t)
ide analogue therapy: results from the randomized controlled
STOP study
Seng Liem1,2, Scott Fung1, David Wong1, Colina Yim1, Jenny Chen1,
Seham Noureldin1, Jordan Feld1,3, Bettina Hansen1,2,4, Harry Janssen1.
1University Health Network, Toronto Centre for Liver Disease, Toronto,
Canada; 2Erasmus University Medical Center Rotterdam, Department of
Gastroenterology and Hepatology, Rotterdam, Netherlands;
3McLaughlin-Rotman Centre for Global Health, Toronto, Canada;
4University of Toronto, Institute of Health Policy, Management and
Evaluation, Toronto, Canada
Email: [email protected]
Background and aims: Patients with chronic hepatitis B (CHB) often
receive long-term nucleos (t)ide analogue (NA) therapy. We compared
outcomes after stopping NA therapy between patients who
started therapy HBeAg positive or negative.
Method: In this prospective single-center randomized controlled
trial, patients were included if they had received tenofovir/entecavir
therapy for ≥ 12 months and achieved virologic suppression (HBeAg
seroconversion and undetectable HBV DNA ≥ 12 months in HBeAg
positive patients, or undetectable HBV DNA ≥ 36 months in HBeAg
negative patients). Patients were randomized 2:1 to either stop or
continue NA therapy for 72 weeks. Retreatment criteriawere: HBeAg
seroreversion, HBV DNA > 20, 000IU/ml twice or HBV DNA > 2, 000
with ALT > 5xULN twice. Sustained response (HBeAg negative, HBV
DNA < 2, 000 IU/ml and normal ALT) was determined at week 72.Results: Of 67 patients (60% male, 97% Asian), 45 (67%) patientswere
assigned to stop and 22 (33%) to continue NA therapy. At start of
therapy, 18/45 (40%) stop patients were HBeAg positive. At randomization
the mean duration of NA therapy was 8 (3) vs. 7 (3) years, 82%
vs. 100% was anti-HBe positive and HBsAg level was 3.2 (0.9) vs. 3.0
(0.6) log IU/ml in HBeAg positive vs. negative patients. Time since
HBeAg loss was 3.8 (2.3) in patients who started therapy as HBeAg
positive. Sustained response was observed in 3/18 (17%) HBeAg
positive vs. 7/27 (26%) negative patients (p = 0.35) (Table). HBsAg loss
occurred in 1 HBeAg-negative patient.
Among patients who stopped, the mean HBsAg change from
randomization to week 72 was −0.1 (0.4) vs. 0.2 (0.2) log IU/ml in
HBeAg positive vs. negative patients (p = 0.10). 11/18 (61%) of the
HBeAg positive vs. 5/27 (19%) HBeAg negative patientswere retreated
by week 72 (p < 0.005). ALT > 1/2/5/10xULN occurred in 89/72/61/
50% vs. 70/48/37/15 % of HBeAg positive vs. negative stop patients.
One HBeAg positive patient developed a bilirubin of 68umol/L, but
none decompensated or died.
Start of therapy
Week 72 outcomes (%)
HBeAg
positiven = 27
HBeAg
negativen = 18 P
Sustained response 17 26 0.35
HBsAg loss 0 4 -
ALT > 5xULN 61 37 0.26
ALT > 10xULN 50 15 0.03
Virologic reactivation (lone
HBV DNA > 20, 000 IU/ml)
83 56 0.14
Clinical relapse (HBV DNA >
2, 000 IU/ml +ALT > 1.5xULN)
6 19 0.10
Conclusion: Start of therapy HBeAg positive patients were more
likely to relapse and receive retreatment than HBeAg negative
patients. These findings in an Asian majority cohort suggest that
patients do not benefit from stopping long-term NA therapy,
particularly those who are HBeAg positive at the start of therapy.

StephenW

PS-056
起病的患者复发率和再治疗率较高
停止长期核后HBeAg阳性比阴性（t）
ide模拟疗法：来自随机对照的结果
停止学习
Seng Liem1,2，Scott Fung1，David Wong1，Colina Yim1，Jenny Chen1，
Seham Noureldin1，Jordan Feld1,3，Bettina Hansen1,2,4，Harry Janssen1。
多伦多多伦多肝脏病中心1大学健康网络，
加拿大; 2鹿特丹伊拉斯姆斯大学医学中心
荷兰鹿特丹的消化内科和肝脏病学;
加拿大多伦多3McLaughlin-Rotman全球健康中心;
4多伦多大学卫生政策，管理和研究所
评价，加拿大多伦多
电子邮件：[email protected]
背景和目的：经常患有慢性乙型肝炎（CHB）的患者
接受长期核苷（酸）类似物（NA）治疗。我们比较了
阻止NA治疗的患者之间的结果
开始治疗HBeAg阳性或阴性。
方法：在这个预期的单中心随机对照
试验，如果他们接受了替诺福韦/恩替卡韦，则纳入患者
治疗≥12个月，实现病毒学抑制（HBeAg
血清转化和HBeAg检测不到HBVDNA≥12个月
阳性患者，或HBeAg检测不到HBVDNA≥36个月
消极的病人）。患者按2：1随机分组至停止或
继续NA治疗72周。再治疗标准是：HBeAg
血清转化，HBV DNA> 20,000IU / ml两次或HBV DNA> 2,000
ALT> 5xULN两次。持续反应（HBeAg阴性，HBV
在第72周测定DNA <2,000IU / ml和正常ALT）。结果：67名患者（60％男性，97％亚洲人），45名（67％）患者
分配停止和22（33％）继续NA治疗。一开始
治疗，18/45（40％）停止患者HBeAg阳性。在随机化
NA治疗的平均持续时间为8（3）vs。7（3）年，82％
相对于100％，抗HBe阳性，HBsAg水平为3.2（0.9）对3.0
（0.6）HBeAg阳性与阴性患者的log IU / ml。时间以来
开始接受HBeAg治疗的患者HBeAg损失为3.8（2.3）
正。在3/18（17％）HBeAg中观察到持续反应
阳性对比7/27（26％）阴性患者（p = 0.35）（表）。 HBsAg丢失
发生于1例HBeAg阴性患者。
停止的患者中，HBsAg的平均值发生变化
随机化至第72周为-0.1（0.4）对0.2（0.2）log IU / ml
HBeAg阳性与阴性患者（p = 0.10）。 11/18（61％）的
HBeAg阳性对比5/27（19％）HBeAg阴性患者复发
到第72周（p <0.005）。 ALT> 1/2/5 / 10xULN发生在89/72/61 /
50％与70/48/37/15％的HBeAg阳性与阴性停止患者相比。
一名HBeAg阳性患者发生了68umol / L的胆红素，但是
没有失代偿或死亡。
开始治疗
第72周结果（％）
大三阳
positiven = 27
大三阳
negativen = 18 P.
持续反应17 26 0.35
HBsAg损失0 4  -
ALT> 5xULN 61 37 0.26
ALT> 10xULN 50 15 0.03
病毒学再激活（孤独的
HBV DNA> 20,000 IU / ml）
83 56 0.14
临床复发（HBV DNA>
2,000 IU / ml + ALT> 1.5xULN）
6 19 0.10
结论：开始治疗的HBeAg阳性患者更多
可能复发并接受再治疗而不是HBeAg阴性
耐心。亚洲多数人群中的这些发现表明
患者不能停止长期NA治疗，
特别是那些在治疗开始时HBeAg阳性的人。