AASLD2014:长期的核苷（酸）类似物IDE巩固治疗减少复发的慢性

StephenW

1856
Long-term Nucleos(t)ide Analogue Consolidation Therapy Reduces Risk of Relapse in Chronic Hepatitis B
Heng Chi1, Bettina E. Hansen1, Pauline Arends1, Mahmoud Abu-Amara2, Colina Yim2, Jordan J. Feld2, Robert J. de Knegt1, David K. Wong2, Harry L. Janssen1,2;
1Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands; 2Toronto Centre for Liver Disease, Toronto Western & General Hospital, University of Toronto, Toronto, ON, Canada

BACKGROUND: The sustainability of response after stopping nucleos(t)ide analogue (NA) therapy in chronic hepatitis B (CHB) patients remains largely unknown. According to international guidelines, 6-12 months of consolidation therapy before stopping NA is associated with increased sustained response. There is however limited evidence whether this is the ideal duration of consolidation therapy.
METHODS: We analyzed 94 patients who stopped NA after at least one year of therapy. Patients could be HBeAg-positive or HBeAg-negative at start-of-therapy, but all were HBeAg-negative and had undetectable HBV DNA (<200 IU/mL) at time of discontinuation. Consolidation therapy was defined as treatment duration between the first undetectable HBV DNA (in case of HBeAg-positive patients after HBeAg loss) and NA discontinuation. Relapse was defined as HBV DNA >2,000 IU/mL measured twice 6 months apart within one year, or retreatment after an initial HBV DNA elevation. RESULTS: Median follow-up was 19.4 months with a median consolidation therapy duration of 2.5 years. At start-of-therapy, 35 patients were HBeAg-positive and 59 were HBeAg-negative. The cumulative relapse rate was 33 %at 6 months, 42.7 %at 1 year, and 64.4 %at 5 years. Start-of-therapy HBeAg-status did not have significant effect on post-treatment relapse even after extensive multivariable analysis. Prolonged consolidation therapy was independently associated with a reduced risk of relapse (Hazard ratio 0.48; 95 %CI 0.24-0.96 for 3 vs. 1 year). Patients with at least 3 years of consolidation therapy (n=37) had a one-year relapse rate of 23.2 %compared to 57.2 %for 1-3 years of consolidation therapy (n=32), and 55.5 %for <1 year of consolidation therapy (n=20)(P=0.002). After NA stop, nine patients lost HBsAg resulting in a five-year cumulative HBsAg loss rate of 15.1%. For each additional year of consolidation therapy, patients were 1.3-fold more likely to lose HBsAg (Hazard ratio 1.34; 95 %CI 1.02-1.75). Two cirrhotic patients developed hepatic decompensation, but there were no deaths.
CONCLUSIONS: Regardless of start-of-therapy HBeAg-status, 64 %of CHB patients experienced a relapse within 5 years after stopping NA. Consolidation therapy of at least 3 years decreased the rate of relapse and increased the rate of HBsAg loss significantly. This study suggests that prolongation of the currently recommended 6-12 months consolidation therapy is needed.

Disclosures:

Colina Yim - Advisory Committees or Review Panels: Merck Canada, Gilead, Janssen

Jordan J. Feld - Advisory Committees or Review Panels: Idenix, Merck, Janssen, Gilead, AbbVie, Merck, Theravance, Bristol Meiers Squibb; Grant/Research Support: AbbVie, Boehringer Ingelheim, Janssen, Gilead, Merck

Robert J. de Knegt - Advisory Committees or Review Panels: MSD, Roche, Norgine, Janssen Cilag; Grant/Research Support: Gilead, MSD, Roche, Janssen Cilag, BMS; Speaking and Teaching: Gilead, MSD, Roche, Janssen Cilag

David K. Wong - Grant/Research Support: Gilead, BMS, Vertex, BI

Harry L. Janssen - Consulting: Abbott, Bristol Myers Squibb, Debio, Gilead Sciences, Merck, Medtronic, Novartis, Roche, Santaris; Grant/Research Support: Anadys, Bristol Myers Squibb, Gilead Sciences, Innogenetics, Kirin, Merck, Medtronic, Novartis, Roche, Santaris

The following people have nothing to disclose: Heng Chi, Bettina E. Hansen, Pauline Arends, Mahmoud Abu-Amara

StephenW

1856
长期的核苷（酸）类似物IDE巩固治疗减少复发的慢性乙型肝炎风险
恒Chi1，贝蒂娜大肠杆菌Hansen1，宝莲Arends1马哈茂德·阿布 -  Amara2，科利纳Yim2，约旦J. Feld2，罗伯特·德Knegt1，大卫K. Wong2，哈利属Janssen1,2;
1Gastroenterology和肝病，伊拉兹马斯MC大学医学中心鹿特丹，荷兰鹿特丹; 2Toronto中心肝病，多伦多西部及综合医院，多伦多大学，多伦多，加拿大

背景：停止核苷（酸）类似物的IDE（NA）治疗慢性乙型肝炎后，响应的可持续性（CHB）患者在很大程度上仍然是未知之数。根据国际准则，巩固治疗停止不适用前6-12个月是增加的持续性反应有关。然而，有证据有限，这是否是巩固治疗的理想时间。
方法：我们分析谁至少一年的治疗后停止不适用94例。患者可能是HBeAg阳性或HBeAg阴性启动时的疗法，但都为HBeAg阴性，并有检测不到HBV DNA（<200 IU/ mL）中的中断时间。巩固治疗被定义为第一个检测不到HBV DNA的治疗时间（在HBeAg阳性患者HBeAg消失后）和NA停药。最初的HBV-DNA升高后一年，或复治内两次测量间隔6个月复发被定义为HBV DNA>2000 IU/ mL的。结果：中位随访时间为19.4个月，2.5年的中位数巩固治疗时间。在启动的疗法，35例HBeAg阳性和59例HBeAg阴性。累积复发率为6个月时为33％，在1年的42.7％，并在5年时64.4％。启动的，治疗的HBeAg状态，即使经过广泛的多变量分析中并没有对治疗后复发显著效果。长期巩固治疗是独立与复发风险降低有关（风险比0.48，95％CI0.24-0.963与1年）。患者至少3年的巩固治疗组（n =37）的有23.2％，一年的复发率相比，57.2％为1-3年的巩固治疗组（n =32），55.5％为<1年巩固治疗组（n =20）（P = 0.002）。 NA停止后，9例失访的HBsAg导致15.1％的五年累计HBsAg消失率。为了巩固治疗每增加一年，患者分别为1.3倍，更容易失去乙肝表面抗原（危险比1.34，95％CI为1.02-1.75）。二肝硬化患者发展为肝功能失代偿，但没有人死亡。
结论：无论起动，治疗的HBeAg状态，64％的慢性乙肝患者出现复发，5年内停止不适用了。在至少3年的巩固治疗，降低复发率和显著增加HBsAg消失率。这项研究表明，需要对目前推荐6-12个月的巩固治疗期延长。

披露：

科利纳炎 - 咨询委员会或审查小组：加拿大默克，吉利德，扬森

乔丹J·费尔德 - 咨询委员会或审查小组：Idenix公司，默克，杨森，基列，AbbVie，默克，Theravance公司，布里斯托尔Meiers施贵宝;格兰特/研究支持：AbbVie，勃林格殷格翰，扬森，Gilead公司，默克公司

罗伯特·德Knegt - 咨询委员会或审查小组：默沙东，罗氏，Norgine，扬森Cilag公司;格兰特/研究支持：Gilead公司，默沙东，罗氏，杨森Cilag公司，拜耳;口语和教学：Gilead公司，默沙东，罗氏，杨森Cilag公司

大卫K.皇 - 格兰特/研究支持：Gilead公司，拜耳，顶点，毕

哈里L.詹森 - 咨询：雅培，施贵宝公司，德彪，Gilead Sciences公司，默克公司，美敦力公司，诺华，罗氏，Santaris;格兰特/研究支持：Anadys公司，施贵宝公司，Gilead科学，Innogenetics公司，麒麟，默克公司，美敦力公司，诺华，罗氏，Santaris

下面的人都没有透露：恒智，贝蒂娜汉森，保罗ARENDS马哈茂德·阿布·阿马拉