HBV Antigen‐Guided Switching Strategy From Nucleos(t)ide Analogue to Interferon: Avoid Virologic Breakthrough and Improve Functional Cure
Little is known for factors associated with virologic breakthrough (VBT) after switching from nucleos(t)ide analogue (NA) to pegylated interferon alpha (Peg‐IFN‐α) for patients with chronic hepatitis B (CHB). Eighty patients who received 48‐week Peg‐IFN‐ɑ and NA combination therapy followed by Peg‐I...
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| Veröffentlicht in: | Journal of medical virology 2024-11, Vol.96 (11), p.e70021-n/a |
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| creator | Huang, Da Yuan, Zhize Wu, Di Yuan, Wei Chang, Jiang Chen, Yuying Ning, Qin Yan, Weiming |
| description | Little is known for factors associated with virologic breakthrough (VBT) after switching from nucleos(t)ide analogue (NA) to pegylated interferon alpha (Peg‐IFN‐α) for patients with chronic hepatitis B (CHB). Eighty patients who received 48‐week Peg‐IFN‐ɑ and NA combination therapy followed by Peg‐IFN‐ɑ monotherapy for additional 48 weeks were included in this study. HBV‐related markers including HBV DNA, HBsAg, HBcrAg, HBeAg, cccDNA, and immunological biomarkers were dynamically evaluated. Twelve (15.0%) patients experienced VBT after switching to Peg‐IFN‐ɑ and exhibited significantly lower rates of HBsAg loss after therapy completion (0% vs. 35.3%, p = 0.014). The patients with HBcrAg≥ 5 log10U/mL and HBsAg≥ 100 IU/mL had the highest risk of VBT and failed to achieve subsequent HBsAg clearance. Intrahepatic cccDNA level was significantly higher in patients with HBcrAg≥ 5 log10U/mL than those with HBcrAg |
| doi_str_mv | 10.1002/jmv.70021 |
| format | Article |
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Eighty patients who received 48‐week Peg‐IFN‐ɑ and NA combination therapy followed by Peg‐IFN‐ɑ monotherapy for additional 48 weeks were included in this study. HBV‐related markers including HBV DNA, HBsAg, HBcrAg, HBeAg, cccDNA, and immunological biomarkers were dynamically evaluated. Twelve (15.0%) patients experienced VBT after switching to Peg‐IFN‐ɑ and exhibited significantly lower rates of HBsAg loss after therapy completion (0% vs. 35.3%, p = 0.014). The patients with HBcrAg≥ 5 log10U/mL and HBsAg≥ 100 IU/mL had the highest risk of VBT and failed to achieve subsequent HBsAg clearance. Intrahepatic cccDNA level was significantly higher in patients with HBcrAg≥ 5 log10U/mL than those with HBcrAg< 5 log10U/mL. Notably, in contrast to patients with HBcrAg< 5 log10U/mL or with HBsAg< 100 IU/mL who had obviously restored HBV‐specific CD8+T cell, Tfh or B cell responses before NA cessation, those with HBcrAg≥ 5 log10U/mL or with HBsAg≥ 100 IU/mL exhibited lackluster immunities before NA cessation and notable diminished immune responses thereafter. Monitoring HBcrAg and HBsAg levels, which correlated with poor immune responses during sequential Peg‐IFN‐ɑ strategy, may help to avoid VBT and improve functional cure of CHB.</description><identifier>ISSN: 0146-6615</identifier><identifier>ISSN: 1096-9071</identifier><identifier>EISSN: 1096-9071</identifier><identifier>DOI: 10.1002/jmv.70021</identifier><identifier>PMID: 39530181</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Adult ; Antiviral Agents - therapeutic use ; Biomarkers ; CD8 antigen ; DNA, Viral - blood ; Drug Substitution ; Drug Therapy, Combination ; Female ; functional cure ; Hepatitis B ; Hepatitis B Antigens - blood ; Hepatitis B Core Antigens - immunology ; Hepatitis B e antigen ; Hepatitis B e Antigens - blood ; Hepatitis B surface antigen ; Hepatitis B Surface Antigens - blood ; Hepatitis B virus - drug effects ; Hepatitis B virus - immunology ; Hepatitis B, Chronic - drug therapy ; Humans ; Immune clearance ; immune response ; Immunology ; Interferon ; Interferon-alpha - therapeutic use ; Lymphocytes ; Lymphocytes T ; Male ; Middle Aged ; NA‐suppressed CHB ; Nucleosides - therapeutic use ; Peg‐IFN‐ɑ ; Strategy ; Treatment Outcome ; virologic breakthrough ; Young Adult</subject><ispartof>Journal of medical virology, 2024-11, Vol.96 (11), p.e70021-n/a</ispartof><rights>2024 Wiley Periodicals LLC.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c2431-991d6d330bf90efe95b191f89abfee45adf7b2f7f6b6d3e5caf3652d6f17fa6f3</cites><orcidid>0000-0002-2027-9593</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjmv.70021$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjmv.70021$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1416,27923,27924,45573,45574</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39530181$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Huang, Da</creatorcontrib><creatorcontrib>Yuan, Zhize</creatorcontrib><creatorcontrib>Wu, Di</creatorcontrib><creatorcontrib>Yuan, Wei</creatorcontrib><creatorcontrib>Chang, Jiang</creatorcontrib><creatorcontrib>Chen, Yuying</creatorcontrib><creatorcontrib>Ning, Qin</creatorcontrib><creatorcontrib>Yan, Weiming</creatorcontrib><title>HBV Antigen‐Guided Switching Strategy From Nucleos(t)ide Analogue to Interferon: Avoid Virologic Breakthrough and Improve Functional Cure</title><title>Journal of medical virology</title><addtitle>J Med Virol</addtitle><description>Little is known for factors associated with virologic breakthrough (VBT) after switching from nucleos(t)ide analogue (NA) to pegylated interferon alpha (Peg‐IFN‐α) for patients with chronic hepatitis B (CHB). Eighty patients who received 48‐week Peg‐IFN‐ɑ and NA combination therapy followed by Peg‐IFN‐ɑ monotherapy for additional 48 weeks were included in this study. HBV‐related markers including HBV DNA, HBsAg, HBcrAg, HBeAg, cccDNA, and immunological biomarkers were dynamically evaluated. Twelve (15.0%) patients experienced VBT after switching to Peg‐IFN‐ɑ and exhibited significantly lower rates of HBsAg loss after therapy completion (0% vs. 35.3%, p = 0.014). The patients with HBcrAg≥ 5 log10U/mL and HBsAg≥ 100 IU/mL had the highest risk of VBT and failed to achieve subsequent HBsAg clearance. Intrahepatic cccDNA level was significantly higher in patients with HBcrAg≥ 5 log10U/mL than those with HBcrAg< 5 log10U/mL. Notably, in contrast to patients with HBcrAg< 5 log10U/mL or with HBsAg< 100 IU/mL who had obviously restored HBV‐specific CD8+T cell, Tfh or B cell responses before NA cessation, those with HBcrAg≥ 5 log10U/mL or with HBsAg≥ 100 IU/mL exhibited lackluster immunities before NA cessation and notable diminished immune responses thereafter. Monitoring HBcrAg and HBsAg levels, which correlated with poor immune responses during sequential Peg‐IFN‐ɑ strategy, may help to avoid VBT and improve functional cure of CHB.</description><subject>Adult</subject><subject>Antiviral Agents - therapeutic use</subject><subject>Biomarkers</subject><subject>CD8 antigen</subject><subject>DNA, Viral - blood</subject><subject>Drug Substitution</subject><subject>Drug Therapy, Combination</subject><subject>Female</subject><subject>functional cure</subject><subject>Hepatitis B</subject><subject>Hepatitis B Antigens - blood</subject><subject>Hepatitis B Core Antigens - immunology</subject><subject>Hepatitis B e antigen</subject><subject>Hepatitis B e Antigens - blood</subject><subject>Hepatitis B surface antigen</subject><subject>Hepatitis B Surface Antigens - blood</subject><subject>Hepatitis B virus - drug effects</subject><subject>Hepatitis B virus - immunology</subject><subject>Hepatitis B, Chronic - drug therapy</subject><subject>Humans</subject><subject>Immune clearance</subject><subject>immune response</subject><subject>Immunology</subject><subject>Interferon</subject><subject>Interferon-alpha - therapeutic use</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Middle Aged</subject><subject>NA‐suppressed CHB</subject><subject>Nucleosides - therapeutic use</subject><subject>Peg‐IFN‐ɑ</subject><subject>Strategy</subject><subject>Treatment Outcome</subject><subject>virologic breakthrough</subject><subject>Young Adult</subject><issn>0146-6615</issn><issn>1096-9071</issn><issn>1096-9071</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10c9uEzEQBnALgWgoHHgBZIlLe9jWs87uxtzSiLRBBQ6FXFfe9XjjsLsu_pMqN-5ceEaeBJcUDkicxtL8_Gmkj5CXwM6Asfx8O-zOqvSAR2QCTJSZYBU8JhMG0zIrSyiOyDPvt4yxmcjzp-SIi4IzmMGEfL-6WNP5GEyH489vPy6jUajozZ0J7caMHb0JTgbs9nTp7EA_xLZH60_CaWLpm-xtF5EGS1djQKfR2fENne-sUXRtnE1r09ILh_JL2Dgbuw2Vo6Kr4dbZHdJlHNtgbIqhi-jwOXmiZe_xxcM8Jp-Xbz8trrLrj5erxfw6a_Mph0wIUKXinDVaMNQoigYE6JmQjUacFlLpqsl1pcsmMSxaqXlZ5KrUUGlZan5MTg656YqvEX2oB-Nb7Hs5oo2-5pDPqkIUDBJ9_Q_d2ujSwfeK8yoHEDyp04NqnfXeoa5vnRmk29fA6vuG6tRQ_buhZF89JMZmQPVX_qkkgfMDuDM97v-fVL97vz5E_gIxQZ0M</recordid><startdate>202411</startdate><enddate>202411</enddate><creator>Huang, Da</creator><creator>Yuan, Zhize</creator><creator>Wu, Di</creator><creator>Yuan, Wei</creator><creator>Chang, Jiang</creator><creator>Chen, Yuying</creator><creator>Ning, Qin</creator><creator>Yan, Weiming</creator><general>Wiley Subscription Services, Inc</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>7QL</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-2027-9593</orcidid></search><sort><creationdate>202411</creationdate><title>HBV Antigen‐Guided Switching Strategy From Nucleos(t)ide Analogue to Interferon: Avoid Virologic Breakthrough and Improve Functional Cure</title><author>Huang, Da ; 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Eighty patients who received 48‐week Peg‐IFN‐ɑ and NA combination therapy followed by Peg‐IFN‐ɑ monotherapy for additional 48 weeks were included in this study. HBV‐related markers including HBV DNA, HBsAg, HBcrAg, HBeAg, cccDNA, and immunological biomarkers were dynamically evaluated. Twelve (15.0%) patients experienced VBT after switching to Peg‐IFN‐ɑ and exhibited significantly lower rates of HBsAg loss after therapy completion (0% vs. 35.3%, p = 0.014). The patients with HBcrAg≥ 5 log10U/mL and HBsAg≥ 100 IU/mL had the highest risk of VBT and failed to achieve subsequent HBsAg clearance. Intrahepatic cccDNA level was significantly higher in patients with HBcrAg≥ 5 log10U/mL than those with HBcrAg< 5 log10U/mL. Notably, in contrast to patients with HBcrAg< 5 log10U/mL or with HBsAg< 100 IU/mL who had obviously restored HBV‐specific CD8+T cell, Tfh or B cell responses before NA cessation, those with HBcrAg≥ 5 log10U/mL or with HBsAg≥ 100 IU/mL exhibited lackluster immunities before NA cessation and notable diminished immune responses thereafter. Monitoring HBcrAg and HBsAg levels, which correlated with poor immune responses during sequential Peg‐IFN‐ɑ strategy, may help to avoid VBT and improve functional cure of CHB.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>39530181</pmid><doi>10.1002/jmv.70021</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-2027-9593</orcidid></addata></record> |
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| subjects | Adult Antiviral Agents - therapeutic use Biomarkers CD8 antigen DNA, Viral - blood Drug Substitution Drug Therapy, Combination Female functional cure Hepatitis B Hepatitis B Antigens - blood Hepatitis B Core Antigens - immunology Hepatitis B e antigen Hepatitis B e Antigens - blood Hepatitis B surface antigen Hepatitis B Surface Antigens - blood Hepatitis B virus - drug effects Hepatitis B virus - immunology Hepatitis B, Chronic - drug therapy Humans Immune clearance immune response Immunology Interferon Interferon-alpha - therapeutic use Lymphocytes Lymphocytes T Male Middle Aged NA‐suppressed CHB Nucleosides - therapeutic use Peg‐IFN‐ɑ Strategy Treatment Outcome virologic breakthrough Young Adult |
| title | HBV Antigen‐Guided Switching Strategy From Nucleos(t)ide Analogue to Interferon: Avoid Virologic Breakthrough and Improve Functional Cure |
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