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Stopping nucleos(t)ide analogue treatment in Caucasian hepatitis B patients after HBeAg seroconversion is associated with high relapse rates and fatal outcomes

Summary Background Stopping nucleos(t)ide analogues (NA) after hepatitis B e antigen (HBeAg) seroconversion is associated with high relapse rates in Asian patients, but data in Caucasian cohorts are scarce. Clinical course, outcomes and immunological aspects of chronic hepatitis B infections differ...

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Published in:Alimentary pharmacology & therapeutics 2018-04, Vol.47 (8), p.1170-1180
Main Authors: Van Hees, S., Bourgeois, S., Van Vlierberghe, H., Sersté, T., Francque, S., Michielsen, P., Sprengers, D., Reynaert, H., Henrion, J., Negrin Dastis, S., Delwaide, J., Lasser, L., Decaestecker, J., Orlent, H., Janssens, F., Robaeys, G., Colle, I., Stärkel, P., Moreno, C., Nevens, F., Vanwolleghem, T., Van Hees, Stijn, Bourgeois, Stefan, Van Vlierberghe, Hans, Sersté, Thomas, Francque, Sven, Michielsen, Peter, Sprengers, Dirk, Reynaert, Hendrik, Henrion, Jean, Negrin‐Dastis, Sergio, Delwaide, Jean, Lasser, Luc, Decaestecker, Jochen, Orlent, Hans, Janssens, Filip, Robaeys, Geert, Colle, Isabelle, Stärkel, Peter, Moreno, Christophe, Nevens, Frederik, Vanwolleghem, Thomas
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container_issue 8
container_start_page 1170
container_title Alimentary pharmacology & therapeutics
container_volume 47
creator Van Hees, S.
Bourgeois, S.
Van Vlierberghe, H.
Sersté, T.
Francque, S.
Michielsen, P.
Sprengers, D.
Reynaert, H.
Henrion, J.
Negrin Dastis, S.
Delwaide, J.
Lasser, L.
Decaestecker, J.
Orlent, H.
Janssens, F.
Robaeys, G.
Colle, I.
Stärkel, P.
Moreno, C.
Nevens, F.
Vanwolleghem, T.
Van Hees, Stijn
Bourgeois, Stefan
Van Vlierberghe, Hans
Sersté, Thomas
Francque, Sven
Michielsen, Peter
Sprengers, Dirk
Reynaert, Hendrik
Henrion, Jean
Negrin‐Dastis, Sergio
Delwaide, Jean
Lasser, Luc
Decaestecker, Jochen
Orlent, Hans
Janssens, Filip
Robaeys, Geert
Colle, Isabelle
Stärkel, Peter
Moreno, Christophe
Nevens, Frederik
Vanwolleghem, Thomas
description Summary Background Stopping nucleos(t)ide analogues (NA) after hepatitis B e antigen (HBeAg) seroconversion is associated with high relapse rates in Asian patients, but data in Caucasian cohorts are scarce. Clinical course, outcomes and immunological aspects of chronic hepatitis B infections differ substantially between distinct ethnicities. Aim The aim of this study was to determine relapse rates, factors predicting relapse and clinical outcomes after nucleos(t)ide analogue cessation in a large, predominantly Caucasian cohort of chronic hepatitis B patients with nucleos(t)ide analogue‐induced HBeAg seroconversion. Methods This is a nationwide observational cohort study including HBeAg positive, mono‐infected chronic hepatitis B patients with nucleos(t)ide analogue‐induced HBeAg seroconversion from 18 centres in Belgium. Results A total of 98 patients with nucleo(s)tide analogue‐induced HBeAg seroconversion were included in the study. Of the 62 patients who stopped treatment after a median consolidation treatment of 8 months, 30 relapsed. Higher gamma‐glutamyl transferase levels at both treatment initiation (HR 1.004; P = 0.001 per unit increment) and HBeAg seroconversion (HR 1.006; P = 0.013 per unit increment) were associated with an increased risk of clinically significant relapse in a multivariate Cox regression model. Treatment cessation led to liver‐related death in 2 patients, of whom one showed a severe flare. Of the patients who continued treatment after HBeAg seroconversion, none relapsed or developed severe hepatic outcomes. Conclusion Treatment withdrawal in Caucasian chronic hepatitis B patients after nucleos(t)ide analogue‐induced HBeAg seroconversion results in viral relapses in more than half of patients with potential fatal outcomes. These real‐world data further lend support to preferentially continue NA treatment after HBeAg seroconversion until HBsAg loss. Linked ContentThis article is linked to Ingiliz and Canbay paper. To view this article visit https://doi.org/10.1111/apt.14649.
doi_str_mv 10.1111/apt.14560
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Clinical course, outcomes and immunological aspects of chronic hepatitis B infections differ substantially between distinct ethnicities. Aim The aim of this study was to determine relapse rates, factors predicting relapse and clinical outcomes after nucleos(t)ide analogue cessation in a large, predominantly Caucasian cohort of chronic hepatitis B patients with nucleos(t)ide analogue‐induced HBeAg seroconversion. Methods This is a nationwide observational cohort study including HBeAg positive, mono‐infected chronic hepatitis B patients with nucleos(t)ide analogue‐induced HBeAg seroconversion from 18 centres in Belgium. Results A total of 98 patients with nucleo(s)tide analogue‐induced HBeAg seroconversion were included in the study. Of the 62 patients who stopped treatment after a median consolidation treatment of 8 months, 30 relapsed. Higher gamma‐glutamyl transferase levels at both treatment initiation (HR 1.004; P = 0.001 per unit increment) and HBeAg seroconversion (HR 1.006; P = 0.013 per unit increment) were associated with an increased risk of clinically significant relapse in a multivariate Cox regression model. Treatment cessation led to liver‐related death in 2 patients, of whom one showed a severe flare. Of the patients who continued treatment after HBeAg seroconversion, none relapsed or developed severe hepatic outcomes. Conclusion Treatment withdrawal in Caucasian chronic hepatitis B patients after nucleos(t)ide analogue‐induced HBeAg seroconversion results in viral relapses in more than half of patients with potential fatal outcomes. These real‐world data further lend support to preferentially continue NA treatment after HBeAg seroconversion until HBsAg loss. Linked ContentThis article is linked to Ingiliz and Canbay paper. To view this article visit https://doi.org/10.1111/apt.14649.</description><identifier>ISSN: 0269-2813</identifier><identifier>EISSN: 1365-2036</identifier><identifier>DOI: 10.1111/apt.14560</identifier><identifier>PMID: 29498078</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Adult ; Analogs ; Antibodies, Viral - blood ; Antiviral Agents - therapeutic use ; Cohort Studies ; Consolidation ; Fatal Outcomes from Stopping Nucleoside Analogues in Hepatitis B ; Female ; Hepatitis ; Hepatitis B ; Hepatitis B e antigen ; Hepatitis B e Antigens - immunology ; Hepatitis B surface antigen ; Hepatitis B virus - immunology ; Hepatitis B, Chronic - blood ; Hepatitis B, Chronic - drug therapy ; Hepatitis B, Chronic - immunology ; Humans ; Immunology ; Interferon ; Liver ; Male ; Middle Aged ; Nucleosides - therapeutic use ; Original ; Patients ; Recurrence ; Seroconversion ; Treatment Outcome ; White people ; Withholding Treatment</subject><ispartof>Alimentary pharmacology &amp; therapeutics, 2018-04, Vol.47 (8), p.1170-1180</ispartof><rights>2018 The Authors. published by John Wiley &amp; Sons Ltd.</rights><rights>2018 The Authors. Alimentary Pharmacology &amp; Therapeutics published by John Wiley &amp; Sons Ltd.</rights><rights>Copyright © 2018 John Wiley &amp; Sons Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><orcidid>0000-0003-4296-8493</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29498078$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Van Hees, S.</creatorcontrib><creatorcontrib>Bourgeois, S.</creatorcontrib><creatorcontrib>Van Vlierberghe, H.</creatorcontrib><creatorcontrib>Sersté, T.</creatorcontrib><creatorcontrib>Francque, S.</creatorcontrib><creatorcontrib>Michielsen, P.</creatorcontrib><creatorcontrib>Sprengers, D.</creatorcontrib><creatorcontrib>Reynaert, H.</creatorcontrib><creatorcontrib>Henrion, J.</creatorcontrib><creatorcontrib>Negrin Dastis, S.</creatorcontrib><creatorcontrib>Delwaide, J.</creatorcontrib><creatorcontrib>Lasser, L.</creatorcontrib><creatorcontrib>Decaestecker, J.</creatorcontrib><creatorcontrib>Orlent, H.</creatorcontrib><creatorcontrib>Janssens, F.</creatorcontrib><creatorcontrib>Robaeys, G.</creatorcontrib><creatorcontrib>Colle, I.</creatorcontrib><creatorcontrib>Stärkel, P.</creatorcontrib><creatorcontrib>Moreno, C.</creatorcontrib><creatorcontrib>Nevens, F.</creatorcontrib><creatorcontrib>Vanwolleghem, T.</creatorcontrib><creatorcontrib>Van Hees, Stijn</creatorcontrib><creatorcontrib>Bourgeois, Stefan</creatorcontrib><creatorcontrib>Van Vlierberghe, Hans</creatorcontrib><creatorcontrib>Sersté, Thomas</creatorcontrib><creatorcontrib>Francque, Sven</creatorcontrib><creatorcontrib>Michielsen, Peter</creatorcontrib><creatorcontrib>Sprengers, Dirk</creatorcontrib><creatorcontrib>Reynaert, Hendrik</creatorcontrib><creatorcontrib>Henrion, Jean</creatorcontrib><creatorcontrib>Negrin‐Dastis, Sergio</creatorcontrib><creatorcontrib>Delwaide, Jean</creatorcontrib><creatorcontrib>Lasser, Luc</creatorcontrib><creatorcontrib>Decaestecker, Jochen</creatorcontrib><creatorcontrib>Orlent, Hans</creatorcontrib><creatorcontrib>Janssens, Filip</creatorcontrib><creatorcontrib>Robaeys, Geert</creatorcontrib><creatorcontrib>Colle, Isabelle</creatorcontrib><creatorcontrib>Stärkel, Peter</creatorcontrib><creatorcontrib>Moreno, Christophe</creatorcontrib><creatorcontrib>Nevens, Frederik</creatorcontrib><creatorcontrib>Vanwolleghem, Thomas</creatorcontrib><creatorcontrib>Belgian NA Stop Study Group</creatorcontrib><title>Stopping nucleos(t)ide analogue treatment in Caucasian hepatitis B patients after HBeAg seroconversion is associated with high relapse rates and fatal outcomes</title><title>Alimentary pharmacology &amp; therapeutics</title><addtitle>Aliment Pharmacol Ther</addtitle><description>Summary Background Stopping nucleos(t)ide analogues (NA) after hepatitis B e antigen (HBeAg) seroconversion is associated with high relapse rates in Asian patients, but data in Caucasian cohorts are scarce. Clinical course, outcomes and immunological aspects of chronic hepatitis B infections differ substantially between distinct ethnicities. Aim The aim of this study was to determine relapse rates, factors predicting relapse and clinical outcomes after nucleos(t)ide analogue cessation in a large, predominantly Caucasian cohort of chronic hepatitis B patients with nucleos(t)ide analogue‐induced HBeAg seroconversion. Methods This is a nationwide observational cohort study including HBeAg positive, mono‐infected chronic hepatitis B patients with nucleos(t)ide analogue‐induced HBeAg seroconversion from 18 centres in Belgium. Results A total of 98 patients with nucleo(s)tide analogue‐induced HBeAg seroconversion were included in the study. Of the 62 patients who stopped treatment after a median consolidation treatment of 8 months, 30 relapsed. Higher gamma‐glutamyl transferase levels at both treatment initiation (HR 1.004; P = 0.001 per unit increment) and HBeAg seroconversion (HR 1.006; P = 0.013 per unit increment) were associated with an increased risk of clinically significant relapse in a multivariate Cox regression model. Treatment cessation led to liver‐related death in 2 patients, of whom one showed a severe flare. Of the patients who continued treatment after HBeAg seroconversion, none relapsed or developed severe hepatic outcomes. Conclusion Treatment withdrawal in Caucasian chronic hepatitis B patients after nucleos(t)ide analogue‐induced HBeAg seroconversion results in viral relapses in more than half of patients with potential fatal outcomes. These real‐world data further lend support to preferentially continue NA treatment after HBeAg seroconversion until HBsAg loss. Linked ContentThis article is linked to Ingiliz and Canbay paper. 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Bourgeois, S. ; Van Vlierberghe, H. ; Sersté, T. ; Francque, S. ; Michielsen, P. ; Sprengers, D. ; Reynaert, H. ; Henrion, J. ; Negrin Dastis, S. ; Delwaide, J. ; Lasser, L. ; Decaestecker, J. ; Orlent, H. ; Janssens, F. ; Robaeys, G. ; Colle, I. ; Stärkel, P. ; Moreno, C. ; Nevens, F. ; Vanwolleghem, T. ; Van Hees, Stijn ; Bourgeois, Stefan ; Van Vlierberghe, Hans ; Sersté, Thomas ; Francque, Sven ; Michielsen, Peter ; Sprengers, Dirk ; Reynaert, Hendrik ; Henrion, Jean ; Negrin‐Dastis, Sergio ; Delwaide, Jean ; Lasser, Luc ; Decaestecker, Jochen ; Orlent, Hans ; Janssens, Filip ; Robaeys, Geert ; Colle, Isabelle ; Stärkel, Peter ; Moreno, Christophe ; Nevens, Frederik ; Vanwolleghem, Thomas</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p3690-bd952214a757c975acd78f7fb8d78575b4af90e83f99d950648f5fed3d870ac43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adult</topic><topic>Analogs</topic><topic>Antibodies, Viral - blood</topic><topic>Antiviral Agents - therapeutic use</topic><topic>Cohort Studies</topic><topic>Consolidation</topic><topic>Fatal Outcomes from Stopping Nucleoside Analogues in Hepatitis B</topic><topic>Female</topic><topic>Hepatitis</topic><topic>Hepatitis B</topic><topic>Hepatitis B e antigen</topic><topic>Hepatitis B e Antigens - immunology</topic><topic>Hepatitis B surface antigen</topic><topic>Hepatitis B virus - immunology</topic><topic>Hepatitis B, Chronic - blood</topic><topic>Hepatitis B, Chronic - drug therapy</topic><topic>Hepatitis B, Chronic - immunology</topic><topic>Humans</topic><topic>Immunology</topic><topic>Interferon</topic><topic>Liver</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Nucleosides - therapeutic use</topic><topic>Original</topic><topic>Patients</topic><topic>Recurrence</topic><topic>Seroconversion</topic><topic>Treatment Outcome</topic><topic>White people</topic><topic>Withholding Treatment</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Van Hees, S.</creatorcontrib><creatorcontrib>Bourgeois, S.</creatorcontrib><creatorcontrib>Van Vlierberghe, H.</creatorcontrib><creatorcontrib>Sersté, T.</creatorcontrib><creatorcontrib>Francque, S.</creatorcontrib><creatorcontrib>Michielsen, P.</creatorcontrib><creatorcontrib>Sprengers, D.</creatorcontrib><creatorcontrib>Reynaert, H.</creatorcontrib><creatorcontrib>Henrion, J.</creatorcontrib><creatorcontrib>Negrin Dastis, S.</creatorcontrib><creatorcontrib>Delwaide, J.</creatorcontrib><creatorcontrib>Lasser, L.</creatorcontrib><creatorcontrib>Decaestecker, J.</creatorcontrib><creatorcontrib>Orlent, H.</creatorcontrib><creatorcontrib>Janssens, F.</creatorcontrib><creatorcontrib>Robaeys, G.</creatorcontrib><creatorcontrib>Colle, I.</creatorcontrib><creatorcontrib>Stärkel, P.</creatorcontrib><creatorcontrib>Moreno, C.</creatorcontrib><creatorcontrib>Nevens, F.</creatorcontrib><creatorcontrib>Vanwolleghem, T.</creatorcontrib><creatorcontrib>Van Hees, Stijn</creatorcontrib><creatorcontrib>Bourgeois, Stefan</creatorcontrib><creatorcontrib>Van Vlierberghe, Hans</creatorcontrib><creatorcontrib>Sersté, Thomas</creatorcontrib><creatorcontrib>Francque, Sven</creatorcontrib><creatorcontrib>Michielsen, Peter</creatorcontrib><creatorcontrib>Sprengers, Dirk</creatorcontrib><creatorcontrib>Reynaert, Hendrik</creatorcontrib><creatorcontrib>Henrion, Jean</creatorcontrib><creatorcontrib>Negrin‐Dastis, Sergio</creatorcontrib><creatorcontrib>Delwaide, Jean</creatorcontrib><creatorcontrib>Lasser, Luc</creatorcontrib><creatorcontrib>Decaestecker, Jochen</creatorcontrib><creatorcontrib>Orlent, Hans</creatorcontrib><creatorcontrib>Janssens, Filip</creatorcontrib><creatorcontrib>Robaeys, Geert</creatorcontrib><creatorcontrib>Colle, Isabelle</creatorcontrib><creatorcontrib>Stärkel, Peter</creatorcontrib><creatorcontrib>Moreno, Christophe</creatorcontrib><creatorcontrib>Nevens, Frederik</creatorcontrib><creatorcontrib>Vanwolleghem, Thomas</creatorcontrib><creatorcontrib>Belgian NA Stop Study Group</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Alimentary pharmacology &amp; therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Van Hees, S.</au><au>Bourgeois, S.</au><au>Van Vlierberghe, H.</au><au>Sersté, T.</au><au>Francque, S.</au><au>Michielsen, P.</au><au>Sprengers, D.</au><au>Reynaert, H.</au><au>Henrion, J.</au><au>Negrin Dastis, S.</au><au>Delwaide, J.</au><au>Lasser, L.</au><au>Decaestecker, J.</au><au>Orlent, H.</au><au>Janssens, F.</au><au>Robaeys, G.</au><au>Colle, I.</au><au>Stärkel, P.</au><au>Moreno, C.</au><au>Nevens, F.</au><au>Vanwolleghem, T.</au><au>Van Hees, Stijn</au><au>Bourgeois, Stefan</au><au>Van Vlierberghe, Hans</au><au>Sersté, Thomas</au><au>Francque, Sven</au><au>Michielsen, Peter</au><au>Sprengers, Dirk</au><au>Reynaert, Hendrik</au><au>Henrion, Jean</au><au>Negrin‐Dastis, Sergio</au><au>Delwaide, Jean</au><au>Lasser, Luc</au><au>Decaestecker, Jochen</au><au>Orlent, Hans</au><au>Janssens, Filip</au><au>Robaeys, Geert</au><au>Colle, Isabelle</au><au>Stärkel, Peter</au><au>Moreno, Christophe</au><au>Nevens, Frederik</au><au>Vanwolleghem, Thomas</au><aucorp>Belgian NA Stop Study Group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Stopping nucleos(t)ide analogue treatment in Caucasian hepatitis B patients after HBeAg seroconversion is associated with high relapse rates and fatal outcomes</atitle><jtitle>Alimentary pharmacology &amp; therapeutics</jtitle><addtitle>Aliment Pharmacol Ther</addtitle><date>2018-04</date><risdate>2018</risdate><volume>47</volume><issue>8</issue><spage>1170</spage><epage>1180</epage><pages>1170-1180</pages><issn>0269-2813</issn><eissn>1365-2036</eissn><abstract>Summary Background Stopping nucleos(t)ide analogues (NA) after hepatitis B e antigen (HBeAg) seroconversion is associated with high relapse rates in Asian patients, but data in Caucasian cohorts are scarce. Clinical course, outcomes and immunological aspects of chronic hepatitis B infections differ substantially between distinct ethnicities. Aim The aim of this study was to determine relapse rates, factors predicting relapse and clinical outcomes after nucleos(t)ide analogue cessation in a large, predominantly Caucasian cohort of chronic hepatitis B patients with nucleos(t)ide analogue‐induced HBeAg seroconversion. Methods This is a nationwide observational cohort study including HBeAg positive, mono‐infected chronic hepatitis B patients with nucleos(t)ide analogue‐induced HBeAg seroconversion from 18 centres in Belgium. Results A total of 98 patients with nucleo(s)tide analogue‐induced HBeAg seroconversion were included in the study. Of the 62 patients who stopped treatment after a median consolidation treatment of 8 months, 30 relapsed. Higher gamma‐glutamyl transferase levels at both treatment initiation (HR 1.004; P = 0.001 per unit increment) and HBeAg seroconversion (HR 1.006; P = 0.013 per unit increment) were associated with an increased risk of clinically significant relapse in a multivariate Cox regression model. Treatment cessation led to liver‐related death in 2 patients, of whom one showed a severe flare. Of the patients who continued treatment after HBeAg seroconversion, none relapsed or developed severe hepatic outcomes. Conclusion Treatment withdrawal in Caucasian chronic hepatitis B patients after nucleos(t)ide analogue‐induced HBeAg seroconversion results in viral relapses in more than half of patients with potential fatal outcomes. These real‐world data further lend support to preferentially continue NA treatment after HBeAg seroconversion until HBsAg loss. Linked ContentThis article is linked to Ingiliz and Canbay paper. To view this article visit https://doi.org/10.1111/apt.14649.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>29498078</pmid><doi>10.1111/apt.14560</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0003-4296-8493</orcidid><oa>free_for_read</oa></addata></record>
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identifier ISSN: 0269-2813
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issn 0269-2813
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language eng
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source Wiley-Blackwell Read & Publish Collection
subjects Adult
Analogs
Antibodies, Viral - blood
Antiviral Agents - therapeutic use
Cohort Studies
Consolidation
Fatal Outcomes from Stopping Nucleoside Analogues in Hepatitis B
Female
Hepatitis
Hepatitis B
Hepatitis B e antigen
Hepatitis B e Antigens - immunology
Hepatitis B surface antigen
Hepatitis B virus - immunology
Hepatitis B, Chronic - blood
Hepatitis B, Chronic - drug therapy
Hepatitis B, Chronic - immunology
Humans
Immunology
Interferon
Liver
Male
Middle Aged
Nucleosides - therapeutic use
Original
Patients
Recurrence
Seroconversion
Treatment Outcome
White people
Withholding Treatment
title Stopping nucleos(t)ide analogue treatment in Caucasian hepatitis B patients after HBeAg seroconversion is associated with high relapse rates and fatal outcomes
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