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
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。