AASLD2017 [934] 核酸停止（t）ide模拟治疗 HBeAg血清转换后相关

StephenW

AASLD2017[934]
Cessation of Nucleos(t)ide Analogue treatment
after HBeAg seroconversion is associated
with a 4-fold increased risk of relapse in
cirrhotic compared to non-cirrhotic patients
Stijn Van Hees1,2, Stefan Bourgeois1,3, Hans Van
Vlierberghe4, Thomas Sersté5, Sven Francque1,2,
Peter P. Michielsen1,2, Sprengers Dirk6, Hendrik Reynaert7,
Jean Henrion8, Sergio Negrin Dastis9, Jean Delwaide10,
Luc Lasser11, Jochen Decaestecker12, Hans Orlent13, Filip Janssens14,
Geert Robaeys15,16, Isabelle Colle17, Peter Starkel18,
Christophe Moreno19, Frederik Nevens20, Thomas Vanwolleghem1,2;
1Department of Gastroenterology and Hepatology,
Antwerp University Hospital, Antwerp, Belgium; 2Laboratory
of Experimental Medicine and Pediatrics, Antwerp University,
Antwerp, Belgium; 3Department of Gastroenterology
and Hepatology, ZNA Antwerp, Antwerp, Belgium; 4Department
of Gastroenterology and Hepatology, Ghent University
Hospital, Ghent, Belgium; 5Department of Gastroenterology
and Hepatology, Saint-Pierre University Hospital, Brussels,
Belgium; 6Department of Gastroenterology and Hepatology,
GZA Antwerp, Antwerp, Belgium; 7Department of Gastroenterology
and Hepatology, VUB University Hospital Brussels,
Brussels, Belgium; 8Department of Gastroenterology and
Hepatology, Hôpital de Jolimont, Jolimont, Belgium; 9Department
of Gastroenterology and Hepatology, Grand Hôpital de
Charleroi, Charleroi, Belgium; 10Department of Gastroenterology
and Hepatology, CHU de Liège, Liège, Belgium; 11Department
of Gastroenterology and Hepatology, CHU Brugmann
Brussels, Brussels, Belgium; 12Department of Gastroenterology
and Hepatology, AZ Delta, Roeselare, Belgium; 13Department
of Gastroenterology and Hepatology, AZ Sint-Jan, Brugge,
Belgium; 14Department of Gastroenterology and Hepatology,
Jessa Hospital, Hasselt, Belgium; 15Department of Gastroenterology
and Hepatology, Ziekenhuis Oost-Limburg, Genk,
Belgium; 16Department of Medicine and Life sciences, Hasselt
University, Hasselt, Belgium; 17Department of Gastroenterology
and Hepatology, ASZ Aalst, Aalst, Belgium; 18Department
of Gastroenterology and Hepatology, Cliniques Universitaires
Saint-Luc, Brussels, Belgium; 19Department of Gastroenterology,
Hepatopancreatology and Digestive Oncology,
CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels,
Belgium; 20Department of Hepatology, University Hospitals
KULeuven, Leuven, Belgium
Background: Cessation of Nucleo(s)tide Analogue (NA)
therapy after HBeAg seroconversion is associated with high
relapse rates. Factors predictive for relapse in Caucasian
patients are not well known. We investigated relapse rates
and factors predictive for relapse after NA stop in a large
multicenter cohort of HBeAg positive Chronic Hepatitis
B (CHB) patients. Methods: This is a multicenter, pooled
analysis of non-immune-suppressed HBeAg-positive,
mono-infected CHB patients treated with different NA for
>= 3 months. Data were collected between 1998 and 2017.
Virologic relapse was defined as HBV DNA>2000 IU/mL;
biochemical relapse as ALT>2xULN (with ULN=40 IU/mL).
Metavir score was histologically graded at start of treatment.
Cox regression model was used to identify predictive
factors for HBeAg seroconversion on treatment and
relapse after treatment stop. Follow-up time was calculated
as respectively time from treatment start to HBeAg
seroconversion or last follow-up and time from HBeAg
seroconversion to relapse or last follow-up. Results: A total
of 356 patients (75.3% male; 63% Caucasian; 16% African)
were included; 115 (32%) of whom showed HBeAg seroconversion
after a median treatment time of 17.7 months.
Rapid, persistent HBV DNA suppression was predictive
for HBeAg seroconversion (HR 0.955; p<0.001 per month
increment) when results were adjusted for the presence
of cirrhosis, HBV DNA and ALT levels at start of treatment
in a multivariate Cox regression model. Treatment
was stopped in 70 patients (of whom 11 were cirrhotic at
baseline) after HBeAg seroconversion and a subsequent
median consolidation therapy of 8.8 months. The median
follow-up duration after treatment stop was 3.0 years
during which 30 patients (43%) showed relapse (16 solely
virologic, 14 combined biochemical and virologic), necessitating
retreatment in 22 cases. HBeAg seroreversion was
observed in 6/30 (20%) relapsed patients. Multivariate Cox
regression model showed that the presence of cirrhosis
(HR 4.350; p=0.027) at start of treatment predicted relapse
after NA stop when results were adjusted for ethnicity
and age at NA stop. In addition, relapse after NA stop
was accompanied by liver-related death in two patients.
Conclusion: In a predominant Caucasian population, treatment
cessation after HBeAg seroconversion led to relapse
in 43% of the patients within a median follow-up duration
of 3.0 years. Presence of cirrhosis at start of treatment
was associated with a 4-fold increased risk of relapse after
treatment stop. Two relapsed patients showed severe clinical
events leading to liver-related death.
Disclosures:
Stefan Bourgeois - Advisory Committees or Review Panels: MSD, AbbVie,
Gilead; Speaking and Teaching: BMS
Geert Robaeys - Advisory Committees or Review Panels: MSD, Janssens,
Gilead, Abbvie, BMS
Isabelle Colle - Consulting: Promethera; Grant/Research Support: abbvie;
Patent Held/Filed: Trombogenics; Speaking and Teaching: BMS
Christophe Moreno - Consulting: Abbvie, Janssen, Gilead, BMS, MSD; Grant/
Research Support: Janssen, Gilead, Roche, Astellas, Abbvie
Frederik Nevens - Consulting: MSD, CAF, Intercept, Gore, BMS, Abbvie,
Novartis, Durect, Janssens-Cilag, Ono Pharma, Promethera Biosciences,
Gilead; Grant/Research Support: Ferring, Roche, Astellas, Novartis, Janssen-
Cilag, Abbvie, Gilead
The following people have nothing to disclose: Stijn Van Hees, Hans Van
Vlierberghe, Sven Francque, Peter P. Michielsen, Sprengers Dirk,
Hendrik Reynaert, Jean Henrion, Sergio Negrin Dastis, Jean Delwaide,
Jochen Decaestecker, Hans Orlent, Filip Janssens, Peter Starkel,
Thomas Vanwolleghem
935

StephenW

AASLD2017 [934]
核酸停止（t）ide模拟治疗
HBeAg血清转换后相关
复发风险增加4倍
肝硬化相比非肝硬化患者
Stijn Van Hees1,2，Stefan Bourgeois1,3，Hans Van
Vlierberghe4，ThomasSersté5，Sven Francque1,2，
Peter P. Michielsen1,2，Sprengers Dirk6，Hendrik Reynaert7，
Jean Henrion8，Sergio Negrin Dastis9，Jean Delwaide10，
Luc Lasser11，Jochen Decaestecker12，Hans Orlent13，Filip Janssens14，
Geert Robaeys15,16，Isabelle Colle17，Peter Starkel18，
Christophe Moreno19，Frederik Nevens20，Thomas Vanwolleghem1,2;
1胃肠病学与肝病学，
比利时安特卫普安特卫普大学医院2Laboratory
实验医学与儿科学，安特卫普大学，
比利时安特卫普消化内科
和比利时安特卫普ZNA安特卫普肝病学会; 4Department
根特大学胃肠病学和肝病学
比利时根特市医院胃肠病学
和肝病学，圣皮埃尔大学医院，布鲁塞尔，
比利时; 6胃肠病学与肝病学，
GZA安特卫普，比利时安特卫普; 7胃肠病科
和肝病学，布鲁塞尔VUB大学医院，
布鲁塞尔，比利时; 8胃肠病科
肝病学，Jolimont，Jolimont，比利时; 9Department
胃肠病学与肝病学杂志
Charleroi，Charleroi，Belgium; 10胃肠病科
和比利时列日的CHU deLiège肝病学会; 11Department
的胃肠病学和肝病学，CHU Brugmann
布鲁塞尔，比利时布鲁塞尔12胃肠病科
和肝病学，AZ三角洲，Roeselare，比利时; 13Department
胃肠病学与肝病学杂志，AZ Sint-Jan，Brugge，
比利时; 14胃肠病学与肝病学，
比利时哈塞尔特Jessa医院15胃肠病科
和肝病学，Ziekenhuis Oost-Limburg，Genk，
比利时; 16哈特尔特医学与生命科学系
比利时哈瑟尔特大学; 17胃肠病科
和比利时阿尔斯特，ASZ Aalst肝病学家; 18Department
胃肠病学与肝病学，临床大学
圣卢克，布鲁塞尔，比利时; 19胃肠病学，
肝胰腺消化肿瘤学，
CUBHôpitalErasme，布鲁塞尔自由大学，布鲁塞尔，
比利时; 20大学医院肝病科
比利时鲁汶KULeuven
背景：中止潮汐模拟（NA）
HBeAg血清转换后的治疗与高
复发率。预测白种人复发的因素
患者不了解。我们调查复发率
以及在大型NA停止后预测复发的因素
HBeAg阳性慢性肝炎多中心队列
B（CHB）患者。方法：这是一个多中心，合并
分析非免疫抑制HBeAg阳性，
单次感染的CHB患者用不同的NA治疗
> = 3个月。资料收集于1998年至2017年。
病毒性复发定义为HBV DNA> 2000 IU / mL;
生化复发为ALT> 2xULN（ULN = 40 IU / mL）。
Metavir评分在治疗开始时被组织学分级。
Cox回归模型用于识别预测
HBeAg血清学转换的因素在治疗和
治疗后复发停止。计算后续时间
分别从治疗开始到HBeAg
血清学转换或HBeAg的最后随访和时间
血清学转换为复发或最后随访。结果：共计
356名患者（男性75.3％;高加索人63％;非洲16％）
被包括在内其中115例（32％）显示HBeAg血清学转换
中位数治疗时间17.7个月。
快速，持续的HBV DNA抑制是预测的
HBeAg血清学转换（HR 0.955; p <0.001每月
增加）当结果被调整为存在
的肝硬化，HBV DNA和ALT水平
在多元Cox回归模型中。治疗
70例患者停止（其中11例肝硬化
基线）HBeAg血清学转换后
中位巩固治疗8.8个月。中位数
治疗停止后的随访时间为3.0年
其中30例（43％）显示复发（仅16例）
病毒学，14组合生化和病毒学），必需
再治疗22例。 HBeAg血清转换为
在6/30（20％）复发患者中观察到。多变量Cox
回归模型显示肝硬化的存在
（HR 4.350; p = 0.027），治疗开始时预测复发
NA停止后，结果被调整为种族
和NA停止的年龄。此外，NA停止后复发
两名患者伴有肝相关死亡。
结论：在主要白种人群中，治疗
HBeAg血清转换后停止导致复发
43％的患者在中位随访期内
3.0年开始治疗时出现肝硬化
与复发风险增加4倍相关
两例复发患者临床症状严重
事件导致肝脏相关死亡。
披露：
Stefan Bourgeois - 咨询委员会或审查小组：MSD，AbbVie，
Gilead公司;言语与教学：BMS
Geert Robaeys - 咨询委员会或审查小组：MSD，Janssens，
基列，阿维，BMS
Isabelle Colle - 咨询：Promethera;授予/研究支持：abbvie;
专利申请/提交：Trombogenics;言语与教学：BMS
Christophe Moreno - 咨询：Abbvie，Janssen，Gilead，BMS，MSD;格兰特/
研究支持：扬森，吉利德，罗氏，阿斯特拉斯，阿维
Frederik Nevens - 咨询：MSD，CAF，Intercept，Gore，BMS，Abbvie，
诺华公司，Durect，Janssens-Cilag，Ono Pharma，Promethera Biosciences，
Gilead公司;授予/研究支持：Ferring，Roche，Astellas，Novartis，Janssen-
Cilag，Abbvie，Gilead
以下人士没有什么可以披露的：Stijn Van Hees，Hans Van
Vlierberghe，Sven Francque，Peter P. Michielsen，Sprengers Dirk，
亨德里克·雷纳特，亨·亨里昂，塞尔吉奥·内格林·达斯提斯，让·德沃德，
Jochen Decaestecker，Hans Orlent，Filip Janssens，Peter Starkel，
Thomas Vanwolleghem

antiHBVren

Background: Cessation of Nucleo(s)tide Analogue (NA) therapy after HBeAg seroconversion is associated with high relapse rates. Factors predictive for relapse in Caucasian patients are not well known. We investigated relapse rates and factors predictive for relapse after NA stop in a large multicenter cohort of HBeAg positive Chronic Hepatitis B (CHB) patients.
Methods: This is a multicenter, pooled analysis of non-immune-suppressed HBeAg-positive, mono-infected CHB patients treated with different NA for >= 3 months. Data were collected between 1998 and 2017. Virologic relapse was defined as HBV DNA>2000 IU/mL; biochemical relapse as ALT>2xULN (with ULN=40 IU/mL). Metavir score was histologically graded at start of treatment. Cox regression model was used to identify predictive factors for HBeAg seroconversion on treatment and relapse after treatment stop. Follow-up time was calculated as respectively time from treatment start to HBeAg seroconversion or last follow-up and time from HBeAg seroconversion to relapse or last follow-up.
Results: A total of 356 patients (75.3% male; 63% Caucasian; 16% African) were included; 115 (32%) of whom showed HBeAg seroconversion after a median treatment time of 17.7 months. Rapid, persistent HBV DNA suppression was predictive for HBeAg seroconversion (HR 0.955; p<0.001 per month increment) when results were adjusted for the presence of cirrhosis, HBV DNA and ALT levels at start of treatment in a multivariate Cox regression model. Treatment was stopped in 70 patients (of whom 11 were cirrhotic at baseline) after HBeAg seroconversion and a subsequent median consolidation therapy of 8.8 months. The median follow-up duration after treatment stop was 3.0 years during which 30 patients (43%) showed relapse (16 solely virologic, 14 combined biochemical and virologic), necessitating retreatment in 22 cases. HBeAg seroreversion was observed in 6/30 (20%) relapsed patients. Multivariate Cox regression model showed that the presence of cirrhosis (HR 4.350; p=0.027) at start of treatment predicted relapse after NA stop when results were adjusted for ethnicity and age at NA stop. In addition, relapse after NA stop was accompanied by liver-related death in two patients.
Conclusion: In a predominant Caucasian population, treatment cessation after HBeAg seroconversion led to relapse in 43% of the patients within a median follow-up duration of 3.0 years. Presence of cirrhosis at start of treatment was associated with a 4-fold increased risk of relapse after treatment stop. Two relapsed patients showed severe clinical events leading to liver-related death.

背景：中止潮汐HBeAg血清学转换后的模拟（NA）治疗与高复发率相关。预测高加索患者复发的因素尚不清楚。在HBeAg阳性慢性乙型肝炎（CHB）患者的大型多中心队列中，我们调查了NA停止后复发率和预后因素。
方法：这是一项多中心，汇总分析的非免疫抑制HBeAg阳性，单感染CHB患者治疗不同NA>> 3个月。数据收集于1998年至2017年间。病毒性复发定义为HBV DNA> 2000 IU / mL;生化复发为ALT> 2xULN（ULN = 40 IU / mL）。 Metavir评分在治疗开始时被组织学分级。 Cox回归模型用于鉴定治疗停止后治疗和复发的HBeAg血清学转换的预测因素。随访时间分别计算为治疗开始至HBeAg血清转换的时间，或最后随访时间和HBeAg血清学转换至复发或最后随访的时间。
结果：共纳入356例患者（男性为75.3％，白种人为63％，非洲16％）; 115例（32％）患者在17.7个月的中位治疗时间后出现HBeAg血清学转换。在多因素Cox回归模型中，当治疗开始时肝硬化，HBV DNA和ALT水平的存在结果进行调整时，快速，持续的HBV DNA抑制预测HBeAg血清学转换（HR 0.955; p <0.001每月增量）。 HBeAg血清转换后70例患者（其中11例为基线水硬化），随访中位巩固治疗8.8个月。治疗停止后的中位随访时间为3.0年，其中30例（43％）显示复发（16例单独病毒学，14个联合生化和病毒学），需要再次治疗22例。在6/30（20％）复发患者中观察到HBeAg血清反应。多因素Cox回归模型显示，开始治疗后，肝硬化的存在（HR 4.350; p = 0.027）预测NA停止后的复发，NA停止时的种族和年龄进行调整。此外，NA停止后的复发伴有两例患者肝脏相关的死亡。
结论：在高血压人群中，HBeAg血清学转换后的治疗停止导致43％的患者在3.0年的中位随访期内复发。治疗开始时肝硬化的存在与治疗停止后复发的风险增加4倍。两例复发患者出现严重的临床事件，导致肝脏相关死亡。