Composition of HBsAg is predictive of HBsAg loss during treatment in patients with HBeAg-positive chronic hepatitis B
During treatment of chronic HBV infections, loss or seroconversion of the HBV surface antigen (HBsAg) is considered a functional cure. HBsAg consists of the large (LHBs), middle (MHBs), and small surface protein (SHBs) and their relative proportions correlate strongly with disease stage. Our aim was...
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| Veröffentlicht in: | Journal of hepatology 2021-02, Vol.74 (2), p.283-292 |
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| creator | Pfefferkorn, Maria Schott, Tina Böhm, Stephan Deichsel, Danilo Felkel, Christin Gerlich, Wolfram H. Glebe, Dieter Wat, Cynthia Pavlovic, Vedran Heyne, Renate Berg, Thomas van Bömmel, Florian |
| description | During treatment of chronic HBV infections, loss or seroconversion of the HBV surface antigen (HBsAg) is considered a functional cure. HBsAg consists of the large (LHBs), middle (MHBs), and small surface protein (SHBs) and their relative proportions correlate strongly with disease stage. Our aim was to assess the association between HBsAg composition and functional cure during treatment.
A total of 83 patients were retrospectively analyzed. HBsAg loss was achieved by 17/64 patients during nucleos(t)ide analogue (NA) treatment and 3/19 patients following treatment with pegylated interferon-alfa2a (PEG-IFN) for 48 weeks. Sixty-three patients without HBsAg loss were matched as controls. LHBs, MHBs and SHBs were quantified in sera collected before and during treatment.
Before treatment, median MHBs levels were significantly lower in patients with subsequent HBsAg loss than in those without (p = 0.005). During treatment, MHBs and LHBs proportions showed a fast decline in patients with HBsAg loss, but not in patients with HBV e antigen seroconversion only or patients without serologic response. MHBs became undetectable by month 6 of NA treatment in all patients with HBsAg loss, which occurred on average 12.8 ± 8.7 (0–52) months before loss of total HBsAg. Receiver-operating characteristic analyses revealed that the proportion of MHBs was the best early predictor of HBsAg loss before NA treatment (AUC = 0.726, p = 0.019). In patients achieving HBsAg loss with PEG-IFN, the proportions of MHBs and LHBs showed similar kinetics.
Quantification of HBsAg proteins shows promise as a novel tool to predict early treatment response. These assessments may help optimize individual antiviral treatment, increasing the rates of functional cure in chronically HBV-infected patients.
The hepatitis B surface antigen (HBsAg) is a key serum marker for viral replication. Loss of HBsAg is considered stable remission, which can be achieved with antiviral treatments. We have investigated whether the ratios of the different components of HBsAg, namely the large (LHBs) and medium (MHBs) HBsAg during different treatments are associated with the occurrence of HBsAg loss. We found that LHBs and MHBs decrease earlier than total HBsAg before HBsAg loss and we propose LHBs and MHBs as promising novel biomarker candidates for predicting cure of HBV infection.
[Display omitted]
•Ratios of large (L), medium (M) and small (S) HBsAg varied before and during antiviral treatment in patients achieving o |
| doi_str_mv | 10.1016/j.jhep.2020.08.039 |
| format | Article |
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A total of 83 patients were retrospectively analyzed. HBsAg loss was achieved by 17/64 patients during nucleos(t)ide analogue (NA) treatment and 3/19 patients following treatment with pegylated interferon-alfa2a (PEG-IFN) for 48 weeks. Sixty-three patients without HBsAg loss were matched as controls. LHBs, MHBs and SHBs were quantified in sera collected before and during treatment.
Before treatment, median MHBs levels were significantly lower in patients with subsequent HBsAg loss than in those without (p = 0.005). During treatment, MHBs and LHBs proportions showed a fast decline in patients with HBsAg loss, but not in patients with HBV e antigen seroconversion only or patients without serologic response. MHBs became undetectable by month 6 of NA treatment in all patients with HBsAg loss, which occurred on average 12.8 ± 8.7 (0–52) months before loss of total HBsAg. Receiver-operating characteristic analyses revealed that the proportion of MHBs was the best early predictor of HBsAg loss before NA treatment (AUC = 0.726, p = 0.019). In patients achieving HBsAg loss with PEG-IFN, the proportions of MHBs and LHBs showed similar kinetics.
Quantification of HBsAg proteins shows promise as a novel tool to predict early treatment response. These assessments may help optimize individual antiviral treatment, increasing the rates of functional cure in chronically HBV-infected patients.
The hepatitis B surface antigen (HBsAg) is a key serum marker for viral replication. Loss of HBsAg is considered stable remission, which can be achieved with antiviral treatments. We have investigated whether the ratios of the different components of HBsAg, namely the large (LHBs) and medium (MHBs) HBsAg during different treatments are associated with the occurrence of HBsAg loss. We found that LHBs and MHBs decrease earlier than total HBsAg before HBsAg loss and we propose LHBs and MHBs as promising novel biomarker candidates for predicting cure of HBV infection.
[Display omitted]
•Ratios of large (L), medium (M) and small (S) HBsAg varied before and during antiviral treatment in patients achieving or not achieving HBsAg loss.•The proportion of MHBs is a suitable marker for early prediction of HBsAg loss.•Quantification of HBsAg proteins might be a novel tool to predict HBsAg loss early on treatment.•With this tool, treatment approaches may be individualized and HBsAg loss rates increased.</description><identifier>ISSN: 0168-8278</identifier><identifier>EISSN: 1600-0641</identifier><identifier>DOI: 10.1016/j.jhep.2020.08.039</identifier><identifier>PMID: 32931877</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject><![CDATA[Antigens, Surface - analysis ; Antigens, Surface - isolation & purification ; Antiviral Agents - administration & dosage ; Biomarkers, Pharmacological - blood ; ELISA ; Female ; HBsAg composition ; Hepatitis B ; Hepatitis B e antigen ; Hepatitis B surface antigen ; Hepatitis B Surface Antigens - analysis ; Hepatitis B Surface Antigens - blood ; Hepatitis B Surface Antigens - immunology ; Hepatitis B virus - drug effects ; Hepatitis B virus - immunology ; Hepatitis B virus - isolation & purification ; Hepatitis B, Chronic - blood ; Hepatitis B, Chronic - diagnosis ; Hepatitis B, Chronic - drug therapy ; Hepatitis B, Chronic - virology ; Humans ; Interferon-alpha - administration & dosage ; LHBs ; Male ; MHBs ; Middle Aged ; Nucleosides - administration & dosage ; Patient Acuity ; Polyethylene Glycols - administration & dosage ; Predictive Value of Tests ; preS1 ; preS2 ; Recombinant Proteins - administration & dosage ; Retrospective Studies ; Seroconversion - drug effects ; Subviral particles ; Viral Proteins - analysis ; Viral Proteins - isolation & purification]]></subject><ispartof>Journal of hepatology, 2021-02, Vol.74 (2), p.283-292</ispartof><rights>2020 European Association for the Study of the Liver</rights><rights>Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.</rights><rights>Copyright Elsevier Science Ltd. Feb 2021</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c384t-668925906821c337252d50a0d19da0fc6c33e7c4fe58af7179fea4a55444d1223</citedby><cites>FETCH-LOGICAL-c384t-668925906821c337252d50a0d19da0fc6c33e7c4fe58af7179fea4a55444d1223</cites><orcidid>0000-0001-5039-0252 ; 0000-0003-3991-999X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0168827820336205$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32931877$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pfefferkorn, Maria</creatorcontrib><creatorcontrib>Schott, Tina</creatorcontrib><creatorcontrib>Böhm, Stephan</creatorcontrib><creatorcontrib>Deichsel, Danilo</creatorcontrib><creatorcontrib>Felkel, Christin</creatorcontrib><creatorcontrib>Gerlich, Wolfram H.</creatorcontrib><creatorcontrib>Glebe, Dieter</creatorcontrib><creatorcontrib>Wat, Cynthia</creatorcontrib><creatorcontrib>Pavlovic, Vedran</creatorcontrib><creatorcontrib>Heyne, Renate</creatorcontrib><creatorcontrib>Berg, Thomas</creatorcontrib><creatorcontrib>van Bömmel, Florian</creatorcontrib><title>Composition of HBsAg is predictive of HBsAg loss during treatment in patients with HBeAg-positive chronic hepatitis B</title><title>Journal of hepatology</title><addtitle>J Hepatol</addtitle><description>During treatment of chronic HBV infections, loss or seroconversion of the HBV surface antigen (HBsAg) is considered a functional cure. HBsAg consists of the large (LHBs), middle (MHBs), and small surface protein (SHBs) and their relative proportions correlate strongly with disease stage. Our aim was to assess the association between HBsAg composition and functional cure during treatment.
A total of 83 patients were retrospectively analyzed. HBsAg loss was achieved by 17/64 patients during nucleos(t)ide analogue (NA) treatment and 3/19 patients following treatment with pegylated interferon-alfa2a (PEG-IFN) for 48 weeks. Sixty-three patients without HBsAg loss were matched as controls. LHBs, MHBs and SHBs were quantified in sera collected before and during treatment.
Before treatment, median MHBs levels were significantly lower in patients with subsequent HBsAg loss than in those without (p = 0.005). During treatment, MHBs and LHBs proportions showed a fast decline in patients with HBsAg loss, but not in patients with HBV e antigen seroconversion only or patients without serologic response. MHBs became undetectable by month 6 of NA treatment in all patients with HBsAg loss, which occurred on average 12.8 ± 8.7 (0–52) months before loss of total HBsAg. Receiver-operating characteristic analyses revealed that the proportion of MHBs was the best early predictor of HBsAg loss before NA treatment (AUC = 0.726, p = 0.019). In patients achieving HBsAg loss with PEG-IFN, the proportions of MHBs and LHBs showed similar kinetics.
Quantification of HBsAg proteins shows promise as a novel tool to predict early treatment response. These assessments may help optimize individual antiviral treatment, increasing the rates of functional cure in chronically HBV-infected patients.
The hepatitis B surface antigen (HBsAg) is a key serum marker for viral replication. Loss of HBsAg is considered stable remission, which can be achieved with antiviral treatments. We have investigated whether the ratios of the different components of HBsAg, namely the large (LHBs) and medium (MHBs) HBsAg during different treatments are associated with the occurrence of HBsAg loss. We found that LHBs and MHBs decrease earlier than total HBsAg before HBsAg loss and we propose LHBs and MHBs as promising novel biomarker candidates for predicting cure of HBV infection.
[Display omitted]
•Ratios of large (L), medium (M) and small (S) HBsAg varied before and during antiviral treatment in patients achieving or not achieving HBsAg loss.•The proportion of MHBs is a suitable marker for early prediction of HBsAg loss.•Quantification of HBsAg proteins might be a novel tool to predict HBsAg loss early on treatment.•With this tool, treatment approaches may be individualized and HBsAg loss rates increased.</description><subject>Antigens, Surface - analysis</subject><subject>Antigens, Surface - isolation & purification</subject><subject>Antiviral Agents - administration & dosage</subject><subject>Biomarkers, Pharmacological - blood</subject><subject>ELISA</subject><subject>Female</subject><subject>HBsAg composition</subject><subject>Hepatitis B</subject><subject>Hepatitis B e antigen</subject><subject>Hepatitis B surface antigen</subject><subject>Hepatitis B Surface Antigens - analysis</subject><subject>Hepatitis B Surface Antigens - blood</subject><subject>Hepatitis B Surface Antigens - immunology</subject><subject>Hepatitis B virus - drug effects</subject><subject>Hepatitis B virus - immunology</subject><subject>Hepatitis B virus - isolation & purification</subject><subject>Hepatitis B, Chronic - blood</subject><subject>Hepatitis B, Chronic - diagnosis</subject><subject>Hepatitis B, Chronic - drug therapy</subject><subject>Hepatitis B, Chronic - virology</subject><subject>Humans</subject><subject>Interferon-alpha - administration & dosage</subject><subject>LHBs</subject><subject>Male</subject><subject>MHBs</subject><subject>Middle Aged</subject><subject>Nucleosides - administration & dosage</subject><subject>Patient Acuity</subject><subject>Polyethylene Glycols - administration & dosage</subject><subject>Predictive Value of Tests</subject><subject>preS1</subject><subject>preS2</subject><subject>Recombinant Proteins - administration & dosage</subject><subject>Retrospective Studies</subject><subject>Seroconversion - drug effects</subject><subject>Subviral particles</subject><subject>Viral Proteins - analysis</subject><subject>Viral Proteins - isolation & purification</subject><issn>0168-8278</issn><issn>1600-0641</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU-LFDEQxYMo7rj6BTxIwIuXbit_upMGL7ODusKCFz2HmK6eSTPdaZP0it_eDL0qePBURfF7j-I9Ql4yqBmw9u1Yjydcag4catA1iO4R2bEWoIJWssdkVyBdaa70FXmW0ggAAjr5lFwJ3gmmldqR9RCmJSSffZhpGOjtTdofqU90idh7l_09_j2fQ0q0X6OfjzRHtHnCOVM_08VmX9ZEf_h8KjDuj9XmWuTuFMPsHS2_FiwX75vn5MlgzwlfPMxr8vXD-y-H2-ru88dPh_1d5YSWuWpb3fGmg1Zz5oRQvOF9AxZ61vUWBteWIyonB2y0HRRT3YBW2qaRUvaMc3FN3my-SwzfV0zZTD45PJ_tjGFNhkspGqba7oK-_gcdwxrn8p3hDWNCNSXfQvGNcrFkEXEwS_STjT8NA3MpxYzmUoq5lGJAm0306sF6_TZh_0fyu4UCvNsALFnce4wmuZKnKw1EdNn0wf_P_xdqXZyn</recordid><startdate>202102</startdate><enddate>202102</enddate><creator>Pfefferkorn, Maria</creator><creator>Schott, Tina</creator><creator>Böhm, Stephan</creator><creator>Deichsel, Danilo</creator><creator>Felkel, Christin</creator><creator>Gerlich, Wolfram H.</creator><creator>Glebe, Dieter</creator><creator>Wat, Cynthia</creator><creator>Pavlovic, Vedran</creator><creator>Heyne, Renate</creator><creator>Berg, Thomas</creator><creator>van Bömmel, Florian</creator><general>Elsevier B.V</general><general>Elsevier Science Ltd</general><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>7T5</scope><scope>H94</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-5039-0252</orcidid><orcidid>https://orcid.org/0000-0003-3991-999X</orcidid></search><sort><creationdate>202102</creationdate><title>Composition of HBsAg is predictive of HBsAg loss during treatment in patients with HBeAg-positive chronic hepatitis B</title><author>Pfefferkorn, Maria ; Schott, Tina ; Böhm, Stephan ; Deichsel, Danilo ; Felkel, Christin ; Gerlich, Wolfram H. ; Glebe, Dieter ; Wat, Cynthia ; Pavlovic, Vedran ; Heyne, Renate ; Berg, Thomas ; van Bömmel, Florian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c384t-668925906821c337252d50a0d19da0fc6c33e7c4fe58af7179fea4a55444d1223</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Antigens, Surface - analysis</topic><topic>Antigens, Surface - isolation & purification</topic><topic>Antiviral Agents - administration & dosage</topic><topic>Biomarkers, Pharmacological - blood</topic><topic>ELISA</topic><topic>Female</topic><topic>HBsAg composition</topic><topic>Hepatitis B</topic><topic>Hepatitis B e antigen</topic><topic>Hepatitis B surface antigen</topic><topic>Hepatitis B Surface Antigens - analysis</topic><topic>Hepatitis B Surface Antigens - blood</topic><topic>Hepatitis B Surface Antigens - immunology</topic><topic>Hepatitis B virus - drug effects</topic><topic>Hepatitis B virus - immunology</topic><topic>Hepatitis B virus - isolation & purification</topic><topic>Hepatitis B, Chronic - blood</topic><topic>Hepatitis B, Chronic - diagnosis</topic><topic>Hepatitis B, Chronic - drug therapy</topic><topic>Hepatitis B, Chronic - virology</topic><topic>Humans</topic><topic>Interferon-alpha - administration & dosage</topic><topic>LHBs</topic><topic>Male</topic><topic>MHBs</topic><topic>Middle Aged</topic><topic>Nucleosides - administration & dosage</topic><topic>Patient Acuity</topic><topic>Polyethylene Glycols - administration & dosage</topic><topic>Predictive Value of Tests</topic><topic>preS1</topic><topic>preS2</topic><topic>Recombinant Proteins - administration & dosage</topic><topic>Retrospective Studies</topic><topic>Seroconversion - drug effects</topic><topic>Subviral particles</topic><topic>Viral Proteins - analysis</topic><topic>Viral Proteins - isolation & purification</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pfefferkorn, Maria</creatorcontrib><creatorcontrib>Schott, Tina</creatorcontrib><creatorcontrib>Böhm, Stephan</creatorcontrib><creatorcontrib>Deichsel, Danilo</creatorcontrib><creatorcontrib>Felkel, Christin</creatorcontrib><creatorcontrib>Gerlich, Wolfram H.</creatorcontrib><creatorcontrib>Glebe, Dieter</creatorcontrib><creatorcontrib>Wat, Cynthia</creatorcontrib><creatorcontrib>Pavlovic, Vedran</creatorcontrib><creatorcontrib>Heyne, Renate</creatorcontrib><creatorcontrib>Berg, Thomas</creatorcontrib><creatorcontrib>van Bömmel, Florian</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of hepatology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pfefferkorn, Maria</au><au>Schott, Tina</au><au>Böhm, Stephan</au><au>Deichsel, Danilo</au><au>Felkel, Christin</au><au>Gerlich, Wolfram H.</au><au>Glebe, Dieter</au><au>Wat, Cynthia</au><au>Pavlovic, Vedran</au><au>Heyne, Renate</au><au>Berg, Thomas</au><au>van Bömmel, Florian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Composition of HBsAg is predictive of HBsAg loss during treatment in patients with HBeAg-positive chronic hepatitis B</atitle><jtitle>Journal of hepatology</jtitle><addtitle>J Hepatol</addtitle><date>2021-02</date><risdate>2021</risdate><volume>74</volume><issue>2</issue><spage>283</spage><epage>292</epage><pages>283-292</pages><issn>0168-8278</issn><eissn>1600-0641</eissn><abstract>During treatment of chronic HBV infections, loss or seroconversion of the HBV surface antigen (HBsAg) is considered a functional cure. HBsAg consists of the large (LHBs), middle (MHBs), and small surface protein (SHBs) and their relative proportions correlate strongly with disease stage. Our aim was to assess the association between HBsAg composition and functional cure during treatment.
A total of 83 patients were retrospectively analyzed. HBsAg loss was achieved by 17/64 patients during nucleos(t)ide analogue (NA) treatment and 3/19 patients following treatment with pegylated interferon-alfa2a (PEG-IFN) for 48 weeks. Sixty-three patients without HBsAg loss were matched as controls. LHBs, MHBs and SHBs were quantified in sera collected before and during treatment.
Before treatment, median MHBs levels were significantly lower in patients with subsequent HBsAg loss than in those without (p = 0.005). During treatment, MHBs and LHBs proportions showed a fast decline in patients with HBsAg loss, but not in patients with HBV e antigen seroconversion only or patients without serologic response. MHBs became undetectable by month 6 of NA treatment in all patients with HBsAg loss, which occurred on average 12.8 ± 8.7 (0–52) months before loss of total HBsAg. Receiver-operating characteristic analyses revealed that the proportion of MHBs was the best early predictor of HBsAg loss before NA treatment (AUC = 0.726, p = 0.019). In patients achieving HBsAg loss with PEG-IFN, the proportions of MHBs and LHBs showed similar kinetics.
Quantification of HBsAg proteins shows promise as a novel tool to predict early treatment response. These assessments may help optimize individual antiviral treatment, increasing the rates of functional cure in chronically HBV-infected patients.
The hepatitis B surface antigen (HBsAg) is a key serum marker for viral replication. Loss of HBsAg is considered stable remission, which can be achieved with antiviral treatments. We have investigated whether the ratios of the different components of HBsAg, namely the large (LHBs) and medium (MHBs) HBsAg during different treatments are associated with the occurrence of HBsAg loss. We found that LHBs and MHBs decrease earlier than total HBsAg before HBsAg loss and we propose LHBs and MHBs as promising novel biomarker candidates for predicting cure of HBV infection.
[Display omitted]
•Ratios of large (L), medium (M) and small (S) HBsAg varied before and during antiviral treatment in patients achieving or not achieving HBsAg loss.•The proportion of MHBs is a suitable marker for early prediction of HBsAg loss.•Quantification of HBsAg proteins might be a novel tool to predict HBsAg loss early on treatment.•With this tool, treatment approaches may be individualized and HBsAg loss rates increased.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>32931877</pmid><doi>10.1016/j.jhep.2020.08.039</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0001-5039-0252</orcidid><orcidid>https://orcid.org/0000-0003-3991-999X</orcidid></addata></record> |
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| ispartof | Journal of hepatology, 2021-02, Vol.74 (2), p.283-292 |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Antigens, Surface - analysis Antigens, Surface - isolation & purification Antiviral Agents - administration & dosage Biomarkers, Pharmacological - blood ELISA Female HBsAg composition Hepatitis B Hepatitis B e antigen Hepatitis B surface antigen Hepatitis B Surface Antigens - analysis Hepatitis B Surface Antigens - blood Hepatitis B Surface Antigens - immunology Hepatitis B virus - drug effects Hepatitis B virus - immunology Hepatitis B virus - isolation & purification Hepatitis B, Chronic - blood Hepatitis B, Chronic - diagnosis Hepatitis B, Chronic - drug therapy Hepatitis B, Chronic - virology Humans Interferon-alpha - administration & dosage LHBs Male MHBs Middle Aged Nucleosides - administration & dosage Patient Acuity Polyethylene Glycols - administration & dosage Predictive Value of Tests preS1 preS2 Recombinant Proteins - administration & dosage Retrospective Studies Seroconversion - drug effects Subviral particles Viral Proteins - analysis Viral Proteins - isolation & purification |
| title | Composition of HBsAg is predictive of HBsAg loss during treatment in patients with HBeAg-positive chronic hepatitis B |
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