Stopping nucleot(s)ide analogues in non‐cirrhotic HBeAg‐negative chronic hepatitis B patients: HBsAg loss at 96 weeks is associated with low baseline HBsAg levels
Summary Background and Aims Current guidelines recommend long‐term nucleot(s)ide analogue (NA) therapy for patients with HBeAg‐negative chronic hepatitis B (CHB). However, disease remission has been described after stopping NA therapy, as well as HBsAg loss. Methods We performed a prospective multi‐...
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| Veröffentlicht in: | Alimentary pharmacology & therapeutics 2022-07, Vol.56 (2), p.310-320 |
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| creator | Hall, Samuel A. L. Burns, Gareth S. Anagnostou, Despina Vogrin, Sara Sundararajan, Vijaya Ratnam, Dilip Levy, Miriam T. Lubel, John S. Nicoll, Amanda J. Strasser, Simone I. Sievert, William Desmond, Paul V. Ngu, Meng C. Angus, Peter Sinclair, Marie Meredith, Christopher Matthews, Gail Revill, Peter A. Jackson, Kathy Littlejohn, Margaret Bowden, D. Scott Locarnini, Stephen A. Visvanathan, Kumar Thompson, Alexander J. |
| description | Summary
Background and Aims
Current guidelines recommend long‐term nucleot(s)ide analogue (NA) therapy for patients with HBeAg‐negative chronic hepatitis B (CHB). However, disease remission has been described after stopping NA therapy, as well as HBsAg loss.
Methods
We performed a prospective multi‐centre cohort study of stopping NA therapy. Inclusion criteria were HBeAg‐negative CHB, the absence of cirrhosis and HBVDNA |
| doi_str_mv | 10.1111/apt.16968 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2661077823</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2661077823</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3258-dcf284f7aeaee8f79693c900c5c0df692c965dd090f06411bda4d92a0a6d15e83</originalsourceid><addsrcrecordid>eNp1kbtOBCEUhonR6HopfAFDqcUoMDvMYLcab4mJJmo9YeHMLMrCOLBu7GztfAyfyycRXbWTBvKfjy85-RHapmSfpnMgu7hPueDVEhrQnBcZIzlfRgPCuMhYRfM1tB7CPSGEl4StorW8KBgVgg3Q-030XWdci91MWfBxN-wZDVg6aX07g4CNw867j5c3Zfp-4qNR-PwIRm1KHLQymifAatJ7lwYT6FIQTcBH-OsFLobDhIdRi60PAcuIBf94eZ0DPCR1CkLwysgIGs9NnCRqjscygDUOfj_CE9iwiVYaaQNs_dwb6O705Pb4PLu8Ors4Hl1mKmdFlWnVsGrYlBIkQNWUgotcCUJUoYhuuGBK8EJrIkhD-JDSsZZDLZgkkmtaQJVvoN2Ft-v9Y9o_1lMTFFgrHfhZqBnnlJRlxfKE7i1Q1afdemjqrjdT2T_XlNRfxdSpmPq7mMTu_Ghn4ynoP_K3iQQcLIC5sfD8v6keXd8ulJ8QTZ0V</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2661077823</pqid></control><display><type>article</type><title>Stopping nucleot(s)ide analogues in non‐cirrhotic HBeAg‐negative chronic hepatitis B patients: HBsAg loss at 96 weeks is associated with low baseline HBsAg levels</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Wiley Online Library Free Content</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><creator>Hall, Samuel A. L. ; Burns, Gareth S. ; Anagnostou, Despina ; Vogrin, Sara ; Sundararajan, Vijaya ; Ratnam, Dilip ; Levy, Miriam T. ; Lubel, John S. ; Nicoll, Amanda J. ; Strasser, Simone I. ; Sievert, William ; Desmond, Paul V. ; Ngu, Meng C. ; Angus, Peter ; Sinclair, Marie ; Meredith, Christopher ; Matthews, Gail ; Revill, Peter A. ; Jackson, Kathy ; Littlejohn, Margaret ; Bowden, D. Scott ; Locarnini, Stephen A. ; Visvanathan, Kumar ; Thompson, Alexander J.</creator><creatorcontrib>Hall, Samuel A. L. ; Burns, Gareth S. ; Anagnostou, Despina ; Vogrin, Sara ; Sundararajan, Vijaya ; Ratnam, Dilip ; Levy, Miriam T. ; Lubel, John S. ; Nicoll, Amanda J. ; Strasser, Simone I. ; Sievert, William ; Desmond, Paul V. ; Ngu, Meng C. ; Angus, Peter ; Sinclair, Marie ; Meredith, Christopher ; Matthews, Gail ; Revill, Peter A. ; Jackson, Kathy ; Littlejohn, Margaret ; Bowden, D. Scott ; Locarnini, Stephen A. ; Visvanathan, Kumar ; Thompson, Alexander J.</creatorcontrib><description><![CDATA[Summary
Background and Aims
Current guidelines recommend long‐term nucleot(s)ide analogue (NA) therapy for patients with HBeAg‐negative chronic hepatitis B (CHB). However, disease remission has been described after stopping NA therapy, as well as HBsAg loss.
Methods
We performed a prospective multi‐centre cohort study of stopping NA therapy. Inclusion criteria were HBeAg‐negative CHB, the absence of cirrhosis and HBVDNA<lower limit of quantification for ≥18 months. We assessed virological and biochemical outcomes including HBsAg loss, as well as NA restart rates, over 96 weeks.
Results
In total, 110 patients [62% entecavir (ETV); 28% tenofovir (TDF), 10% other] were enrolled. Median age was 56 years, 57% were male, 85% were Asian, median baseline HBsAg level was 705 (214–2325) IU/ml. Virological reactivation occurred in 109/110 patients, median time to detection was 8 (4–12) weeks, and occurred earlier after stopping TDF versus ETV (median 4 vs. 12 weeks p < 0.001). At week 96, 77 (70%) remained off‐treatment, 65 (59%) had ALT <2× ULN, 31 (28%) patients were in disease remission with HBVDNA <2000 IU/ml plus ALT <2× ULN and 7 (6%) patients had lost HBsAg. Baseline HBsAg ≤10 IU/ml was associated with HBsAg loss (6/9 vs. 1/101 p < 0.001). ALT >5× ULN occurred in 35 (32%); ALT flares were not associated with HBsAg loss. There were no unexpected safety issues.
Conclusion
Virological reactivation was very common after stopping NA therapy and occurred earlier after stopping TDF versus ETV. The majority of patients had ALT <2× ULN at week 96, but only one‐third achieved disease remission and HBsAg loss was rare. Very low HBsAg levels at baseline were uncommon but predicted for HBsAg loss and disease remission.
Clinical outcomes over time—Intention to treat analysis of clinical outcomes in 110 patients who stopped NA therapy. Patients were classified into the following groups: HBsAg loss, Biochemical Remission (ALT <2× ULN), Virological Remission (HBV DNA <2000), or NA treatment restarted (Figure 1); Low baseline HBsAg levels were associated with higher likelihood of HBsAg loss and lower rates of Virological and Biochemical Relapse—(A) Baseline HBsAg level ≤10 IU/ml was associated with HBsAg loss – 6 of 7 patients who lost HBsAg had a baseline HBsAg level ≤10 IU/ml [HBsAg ≤10 IU/ml, HBsAg loss = 6/9 (67%) versus HBsAg >10 IU/ml, HBsAg loss = 1/101 (1%), p < 0.001, Figure 5]. Low baseline HBsAg levels were also associated with a lower rate of (B) virological relapse [HBsAg level ≤10 IU/ml, 3/9 vs. HBsAg level >10, 95/101, HR 0.15 (0.05, 0.47) p = 0.001] and (C) biochemical relapse [HBsAg level ≤10 IU/ml, 1/9 vs. HBsAg level >10, 54/101, HR 0.16 (0.02, 1.13) p = 0.066] through 96 weeks of follow‐up (Figure 2).]]></description><identifier>ISSN: 0269-2813</identifier><identifier>EISSN: 1365-2036</identifier><identifier>DOI: 10.1111/apt.16968</identifier><identifier>PMID: 35521992</identifier><language>eng</language><publisher>England</publisher><subject>Antiviral Agents - therapeutic use ; Cohort Studies ; DNA, Viral ; Female ; Hepatitis B e Antigens ; Hepatitis B Surface Antigens ; Hepatitis B virus - genetics ; Hepatitis B, Chronic - diagnosis ; Hepatitis B, Chronic - drug therapy ; Humans ; Male ; Middle Aged ; Prospective Studies ; Treatment Outcome</subject><ispartof>Alimentary pharmacology & therapeutics, 2022-07, Vol.56 (2), p.310-320</ispartof><rights>2022 John Wiley & Sons Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3258-dcf284f7aeaee8f79693c900c5c0df692c965dd090f06411bda4d92a0a6d15e83</citedby><cites>FETCH-LOGICAL-c3258-dcf284f7aeaee8f79693c900c5c0df692c965dd090f06411bda4d92a0a6d15e83</cites><orcidid>0000-0003-0657-3048 ; 0000-0001-7158-585X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fapt.16968$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fapt.16968$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,1427,27901,27902,45550,45551,46384,46808</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35521992$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hall, Samuel A. L.</creatorcontrib><creatorcontrib>Burns, Gareth S.</creatorcontrib><creatorcontrib>Anagnostou, Despina</creatorcontrib><creatorcontrib>Vogrin, Sara</creatorcontrib><creatorcontrib>Sundararajan, Vijaya</creatorcontrib><creatorcontrib>Ratnam, Dilip</creatorcontrib><creatorcontrib>Levy, Miriam T.</creatorcontrib><creatorcontrib>Lubel, John S.</creatorcontrib><creatorcontrib>Nicoll, Amanda J.</creatorcontrib><creatorcontrib>Strasser, Simone I.</creatorcontrib><creatorcontrib>Sievert, William</creatorcontrib><creatorcontrib>Desmond, Paul V.</creatorcontrib><creatorcontrib>Ngu, Meng C.</creatorcontrib><creatorcontrib>Angus, Peter</creatorcontrib><creatorcontrib>Sinclair, Marie</creatorcontrib><creatorcontrib>Meredith, Christopher</creatorcontrib><creatorcontrib>Matthews, Gail</creatorcontrib><creatorcontrib>Revill, Peter A.</creatorcontrib><creatorcontrib>Jackson, Kathy</creatorcontrib><creatorcontrib>Littlejohn, Margaret</creatorcontrib><creatorcontrib>Bowden, D. Scott</creatorcontrib><creatorcontrib>Locarnini, Stephen A.</creatorcontrib><creatorcontrib>Visvanathan, Kumar</creatorcontrib><creatorcontrib>Thompson, Alexander J.</creatorcontrib><title>Stopping nucleot(s)ide analogues in non‐cirrhotic HBeAg‐negative chronic hepatitis B patients: HBsAg loss at 96 weeks is associated with low baseline HBsAg levels</title><title>Alimentary pharmacology & therapeutics</title><addtitle>Aliment Pharmacol Ther</addtitle><description><![CDATA[Summary
Background and Aims
Current guidelines recommend long‐term nucleot(s)ide analogue (NA) therapy for patients with HBeAg‐negative chronic hepatitis B (CHB). However, disease remission has been described after stopping NA therapy, as well as HBsAg loss.
Methods
We performed a prospective multi‐centre cohort study of stopping NA therapy. Inclusion criteria were HBeAg‐negative CHB, the absence of cirrhosis and HBVDNA<lower limit of quantification for ≥18 months. We assessed virological and biochemical outcomes including HBsAg loss, as well as NA restart rates, over 96 weeks.
Results
In total, 110 patients [62% entecavir (ETV); 28% tenofovir (TDF), 10% other] were enrolled. Median age was 56 years, 57% were male, 85% were Asian, median baseline HBsAg level was 705 (214–2325) IU/ml. Virological reactivation occurred in 109/110 patients, median time to detection was 8 (4–12) weeks, and occurred earlier after stopping TDF versus ETV (median 4 vs. 12 weeks p < 0.001). At week 96, 77 (70%) remained off‐treatment, 65 (59%) had ALT <2× ULN, 31 (28%) patients were in disease remission with HBVDNA <2000 IU/ml plus ALT <2× ULN and 7 (6%) patients had lost HBsAg. Baseline HBsAg ≤10 IU/ml was associated with HBsAg loss (6/9 vs. 1/101 p < 0.001). ALT >5× ULN occurred in 35 (32%); ALT flares were not associated with HBsAg loss. There were no unexpected safety issues.
Conclusion
Virological reactivation was very common after stopping NA therapy and occurred earlier after stopping TDF versus ETV. The majority of patients had ALT <2× ULN at week 96, but only one‐third achieved disease remission and HBsAg loss was rare. Very low HBsAg levels at baseline were uncommon but predicted for HBsAg loss and disease remission.
Clinical outcomes over time—Intention to treat analysis of clinical outcomes in 110 patients who stopped NA therapy. Patients were classified into the following groups: HBsAg loss, Biochemical Remission (ALT <2× ULN), Virological Remission (HBV DNA <2000), or NA treatment restarted (Figure 1); Low baseline HBsAg levels were associated with higher likelihood of HBsAg loss and lower rates of Virological and Biochemical Relapse—(A) Baseline HBsAg level ≤10 IU/ml was associated with HBsAg loss – 6 of 7 patients who lost HBsAg had a baseline HBsAg level ≤10 IU/ml [HBsAg ≤10 IU/ml, HBsAg loss = 6/9 (67%) versus HBsAg >10 IU/ml, HBsAg loss = 1/101 (1%), p < 0.001, Figure 5]. Low baseline HBsAg levels were also associated with a lower rate of (B) virological relapse [HBsAg level ≤10 IU/ml, 3/9 vs. HBsAg level >10, 95/101, HR 0.15 (0.05, 0.47) p = 0.001] and (C) biochemical relapse [HBsAg level ≤10 IU/ml, 1/9 vs. HBsAg level >10, 54/101, HR 0.16 (0.02, 1.13) p = 0.066] through 96 weeks of follow‐up (Figure 2).]]></description><subject>Antiviral Agents - therapeutic use</subject><subject>Cohort Studies</subject><subject>DNA, Viral</subject><subject>Female</subject><subject>Hepatitis B e Antigens</subject><subject>Hepatitis B Surface Antigens</subject><subject>Hepatitis B virus - genetics</subject><subject>Hepatitis B, Chronic - diagnosis</subject><subject>Hepatitis B, Chronic - drug therapy</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Prospective Studies</subject><subject>Treatment Outcome</subject><issn>0269-2813</issn><issn>1365-2036</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kbtOBCEUhonR6HopfAFDqcUoMDvMYLcab4mJJmo9YeHMLMrCOLBu7GztfAyfyycRXbWTBvKfjy85-RHapmSfpnMgu7hPueDVEhrQnBcZIzlfRgPCuMhYRfM1tB7CPSGEl4StorW8KBgVgg3Q-030XWdci91MWfBxN-wZDVg6aX07g4CNw867j5c3Zfp-4qNR-PwIRm1KHLQymifAatJ7lwYT6FIQTcBH-OsFLobDhIdRi60PAcuIBf94eZ0DPCR1CkLwysgIGs9NnCRqjscygDUOfj_CE9iwiVYaaQNs_dwb6O705Pb4PLu8Ors4Hl1mKmdFlWnVsGrYlBIkQNWUgotcCUJUoYhuuGBK8EJrIkhD-JDSsZZDLZgkkmtaQJVvoN2Ft-v9Y9o_1lMTFFgrHfhZqBnnlJRlxfKE7i1Q1afdemjqrjdT2T_XlNRfxdSpmPq7mMTu_Ghn4ynoP_K3iQQcLIC5sfD8v6keXd8ulJ8QTZ0V</recordid><startdate>202207</startdate><enddate>202207</enddate><creator>Hall, Samuel A. L.</creator><creator>Burns, Gareth S.</creator><creator>Anagnostou, Despina</creator><creator>Vogrin, Sara</creator><creator>Sundararajan, Vijaya</creator><creator>Ratnam, Dilip</creator><creator>Levy, Miriam T.</creator><creator>Lubel, John S.</creator><creator>Nicoll, Amanda J.</creator><creator>Strasser, Simone I.</creator><creator>Sievert, William</creator><creator>Desmond, Paul V.</creator><creator>Ngu, Meng C.</creator><creator>Angus, Peter</creator><creator>Sinclair, Marie</creator><creator>Meredith, Christopher</creator><creator>Matthews, Gail</creator><creator>Revill, Peter A.</creator><creator>Jackson, Kathy</creator><creator>Littlejohn, Margaret</creator><creator>Bowden, D. Scott</creator><creator>Locarnini, Stephen A.</creator><creator>Visvanathan, Kumar</creator><creator>Thompson, Alexander J.</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-0657-3048</orcidid><orcidid>https://orcid.org/0000-0001-7158-585X</orcidid></search><sort><creationdate>202207</creationdate><title>Stopping nucleot(s)ide analogues in non‐cirrhotic HBeAg‐negative chronic hepatitis B patients: HBsAg loss at 96 weeks is associated with low baseline HBsAg levels</title><author>Hall, Samuel A. L. ; Burns, Gareth S. ; Anagnostou, Despina ; Vogrin, Sara ; Sundararajan, Vijaya ; Ratnam, Dilip ; Levy, Miriam T. ; Lubel, John S. ; Nicoll, Amanda J. ; Strasser, Simone I. ; Sievert, William ; Desmond, Paul V. ; Ngu, Meng C. ; Angus, Peter ; Sinclair, Marie ; Meredith, Christopher ; Matthews, Gail ; Revill, Peter A. ; Jackson, Kathy ; Littlejohn, Margaret ; Bowden, D. Scott ; Locarnini, Stephen A. ; Visvanathan, Kumar ; Thompson, Alexander J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3258-dcf284f7aeaee8f79693c900c5c0df692c965dd090f06411bda4d92a0a6d15e83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Antiviral Agents - therapeutic use</topic><topic>Cohort Studies</topic><topic>DNA, Viral</topic><topic>Female</topic><topic>Hepatitis B e Antigens</topic><topic>Hepatitis B Surface Antigens</topic><topic>Hepatitis B virus - genetics</topic><topic>Hepatitis B, Chronic - diagnosis</topic><topic>Hepatitis B, Chronic - drug therapy</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Prospective Studies</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hall, Samuel A. L.</creatorcontrib><creatorcontrib>Burns, Gareth S.</creatorcontrib><creatorcontrib>Anagnostou, Despina</creatorcontrib><creatorcontrib>Vogrin, Sara</creatorcontrib><creatorcontrib>Sundararajan, Vijaya</creatorcontrib><creatorcontrib>Ratnam, Dilip</creatorcontrib><creatorcontrib>Levy, Miriam T.</creatorcontrib><creatorcontrib>Lubel, John S.</creatorcontrib><creatorcontrib>Nicoll, Amanda J.</creatorcontrib><creatorcontrib>Strasser, Simone I.</creatorcontrib><creatorcontrib>Sievert, William</creatorcontrib><creatorcontrib>Desmond, Paul V.</creatorcontrib><creatorcontrib>Ngu, Meng C.</creatorcontrib><creatorcontrib>Angus, Peter</creatorcontrib><creatorcontrib>Sinclair, Marie</creatorcontrib><creatorcontrib>Meredith, Christopher</creatorcontrib><creatorcontrib>Matthews, Gail</creatorcontrib><creatorcontrib>Revill, Peter A.</creatorcontrib><creatorcontrib>Jackson, Kathy</creatorcontrib><creatorcontrib>Littlejohn, Margaret</creatorcontrib><creatorcontrib>Bowden, D. Scott</creatorcontrib><creatorcontrib>Locarnini, Stephen A.</creatorcontrib><creatorcontrib>Visvanathan, Kumar</creatorcontrib><creatorcontrib>Thompson, Alexander J.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Alimentary pharmacology & therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hall, Samuel A. L.</au><au>Burns, Gareth S.</au><au>Anagnostou, Despina</au><au>Vogrin, Sara</au><au>Sundararajan, Vijaya</au><au>Ratnam, Dilip</au><au>Levy, Miriam T.</au><au>Lubel, John S.</au><au>Nicoll, Amanda J.</au><au>Strasser, Simone I.</au><au>Sievert, William</au><au>Desmond, Paul V.</au><au>Ngu, Meng C.</au><au>Angus, Peter</au><au>Sinclair, Marie</au><au>Meredith, Christopher</au><au>Matthews, Gail</au><au>Revill, Peter A.</au><au>Jackson, Kathy</au><au>Littlejohn, Margaret</au><au>Bowden, D. Scott</au><au>Locarnini, Stephen A.</au><au>Visvanathan, Kumar</au><au>Thompson, Alexander J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Stopping nucleot(s)ide analogues in non‐cirrhotic HBeAg‐negative chronic hepatitis B patients: HBsAg loss at 96 weeks is associated with low baseline HBsAg levels</atitle><jtitle>Alimentary pharmacology & therapeutics</jtitle><addtitle>Aliment Pharmacol Ther</addtitle><date>2022-07</date><risdate>2022</risdate><volume>56</volume><issue>2</issue><spage>310</spage><epage>320</epage><pages>310-320</pages><issn>0269-2813</issn><eissn>1365-2036</eissn><abstract><![CDATA[Summary
Background and Aims
Current guidelines recommend long‐term nucleot(s)ide analogue (NA) therapy for patients with HBeAg‐negative chronic hepatitis B (CHB). However, disease remission has been described after stopping NA therapy, as well as HBsAg loss.
Methods
We performed a prospective multi‐centre cohort study of stopping NA therapy. Inclusion criteria were HBeAg‐negative CHB, the absence of cirrhosis and HBVDNA<lower limit of quantification for ≥18 months. We assessed virological and biochemical outcomes including HBsAg loss, as well as NA restart rates, over 96 weeks.
Results
In total, 110 patients [62% entecavir (ETV); 28% tenofovir (TDF), 10% other] were enrolled. Median age was 56 years, 57% were male, 85% were Asian, median baseline HBsAg level was 705 (214–2325) IU/ml. Virological reactivation occurred in 109/110 patients, median time to detection was 8 (4–12) weeks, and occurred earlier after stopping TDF versus ETV (median 4 vs. 12 weeks p < 0.001). At week 96, 77 (70%) remained off‐treatment, 65 (59%) had ALT <2× ULN, 31 (28%) patients were in disease remission with HBVDNA <2000 IU/ml plus ALT <2× ULN and 7 (6%) patients had lost HBsAg. Baseline HBsAg ≤10 IU/ml was associated with HBsAg loss (6/9 vs. 1/101 p < 0.001). ALT >5× ULN occurred in 35 (32%); ALT flares were not associated with HBsAg loss. There were no unexpected safety issues.
Conclusion
Virological reactivation was very common after stopping NA therapy and occurred earlier after stopping TDF versus ETV. The majority of patients had ALT <2× ULN at week 96, but only one‐third achieved disease remission and HBsAg loss was rare. Very low HBsAg levels at baseline were uncommon but predicted for HBsAg loss and disease remission.
Clinical outcomes over time—Intention to treat analysis of clinical outcomes in 110 patients who stopped NA therapy. Patients were classified into the following groups: HBsAg loss, Biochemical Remission (ALT <2× ULN), Virological Remission (HBV DNA <2000), or NA treatment restarted (Figure 1); Low baseline HBsAg levels were associated with higher likelihood of HBsAg loss and lower rates of Virological and Biochemical Relapse—(A) Baseline HBsAg level ≤10 IU/ml was associated with HBsAg loss – 6 of 7 patients who lost HBsAg had a baseline HBsAg level ≤10 IU/ml [HBsAg ≤10 IU/ml, HBsAg loss = 6/9 (67%) versus HBsAg >10 IU/ml, HBsAg loss = 1/101 (1%), p < 0.001, Figure 5]. Low baseline HBsAg levels were also associated with a lower rate of (B) virological relapse [HBsAg level ≤10 IU/ml, 3/9 vs. HBsAg level >10, 95/101, HR 0.15 (0.05, 0.47) p = 0.001] and (C) biochemical relapse [HBsAg level ≤10 IU/ml, 1/9 vs. HBsAg level >10, 54/101, HR 0.16 (0.02, 1.13) p = 0.066] through 96 weeks of follow‐up (Figure 2).]]></abstract><cop>England</cop><pmid>35521992</pmid><doi>10.1111/apt.16968</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0003-0657-3048</orcidid><orcidid>https://orcid.org/0000-0001-7158-585X</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0269-2813 |
| ispartof | Alimentary pharmacology & therapeutics, 2022-07, Vol.56 (2), p.310-320 |
| issn | 0269-2813 1365-2036 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2661077823 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Wiley Online Library Free Content; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Antiviral Agents - therapeutic use Cohort Studies DNA, Viral Female Hepatitis B e Antigens Hepatitis B Surface Antigens Hepatitis B virus - genetics Hepatitis B, Chronic - diagnosis Hepatitis B, Chronic - drug therapy Humans Male Middle Aged Prospective Studies Treatment Outcome |
| title | Stopping nucleot(s)ide analogues in non‐cirrhotic HBeAg‐negative chronic hepatitis B patients: HBsAg loss at 96 weeks is associated with low baseline HBsAg levels |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-21T12%3A19%3A50IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Stopping%20nucleot(s)ide%20analogues%20in%20non%E2%80%90cirrhotic%20HBeAg%E2%80%90negative%20chronic%20hepatitis%20B%20patients:%20HBsAg%20loss%20at%2096%E2%80%89weeks%20is%20associated%20with%20low%20baseline%20HBsAg%20levels&rft.jtitle=Alimentary%20pharmacology%20&%20therapeutics&rft.au=Hall,%20Samuel%20A.%20L.&rft.date=2022-07&rft.volume=56&rft.issue=2&rft.spage=310&rft.epage=320&rft.pages=310-320&rft.issn=0269-2813&rft.eissn=1365-2036&rft_id=info:doi/10.1111/apt.16968&rft_dat=%3Cproquest_cross%3E2661077823%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2661077823&rft_id=info:pmid/35521992&rfr_iscdi=true |