{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T18:25:18Z","timestamp":1793816718846,"version":"4.6.1"},"reference-count":27,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T00:00:00Z","timestamp":1658448000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Roche Korea"},{"name":"Ministry of Science and ICT","award":["2021R1F1A1052110"],"award-info":[{"award-number":["2021R1F1A1052110"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Aims<\/jats:title>\n<jats:p>Induction of a durable viral response is difficult to achieve in patients with chronic hepatitis B (CHB), even from long-term use of a nucleos(t)ide analogue (NA). This study investigated whether switching to peginterferon (PegIFN) alfa-2a after long-term NA therapy induced a durable viral response.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Patients with hepatitis B e antigen (HBeAg)-positive CHB who received any NA for at least 72 weeks and had a low level of HBV DNA (\u2264100 IU\/mL) were randomized (1:1) to receive PegIFN alfa-2a (180 \u03bcg\/week) or NA for 48 weeks. The primary endpoint was change in the hepatitis B surface antigen (HBsAg) titer during antiviral therapy.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>We randomized 149 CHB patients to the two groups. Compared to baseline, the HBsAg levels in both groups were not lower at week 12, but were lower after 24, 36, and 48 weeks (all p&lt;0.001). The maximal HBsAg decline in the PegIFN alfa-2a group was at week 36 (0.50\u00b10.88 log<jats:sub>10<\/jats:sub> IU\/mL), and this decline was smaller in the NA group (0.08\u00b10.46 log<jats:sub>10<\/jats:sub> IU\/mL). The percentage of patients with HBeAg seroconversion at week 48 was also greater in the PegIFN alfa-2a group (15\/75 [20.0%] <jats:italic>vs<\/jats:italic>. 5\/74 [6.8%], p = 0.018). Multivariable analysis indicated the PegIFN alfa-2a group had a greater change in HBeAg seroconversion at week 48 (p = 0.027). Patients had relatively good tolerance to PegIFN alfa-2a therapy.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>CHB patients who switched to PegIFN alfa-2a for 48 weeks had a significantly lower HBsAg titer and increased HBeAg seroconversion relative to those who remained on NA therapy.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Trial registration<\/jats:title>\n<jats:p>(ClinicalTrials.gov; <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01769833\" xlink:type=\"simple\">NCT01769833<\/jats:ext-link>).<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0270716","type":"journal-article","created":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T17:37:37Z","timestamp":1658511457000},"page":"e0270716","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Effect of switching from nucleos(t)ide maintenance therapy to PegIFN alfa-2a in patients with HBeAg-positive chronic hepatitis B: A randomized trial"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0605-6318","authenticated-orcid":true,"given":"Hyun Young","family":"Woo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0961-7851","authenticated-orcid":true,"given":"Jeong","family":"Heo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won Young","family":"Tak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heon Ju","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woo Jin","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Gil","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo Young","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Joo","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu Rim","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Seok","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Oh","family":"Kweon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,7,22]]},"reference":[{"key":"pone.0270716.ref001","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1002\/hep.23327","article-title":"Entecavir treatment for up to 5 years in patients with hepatitis B e antigen-positive chronic hepatitis B","volume":"51","author":"TT Chang","year":"2010","journal-title":"Hepatology"},{"key":"pone.0270716.ref002","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1002\/hep.23785","article-title":"Long-term entecavir therapy results in the reversal of fibrosis\/cirrhosis and continued histological improvement in patients with chronic hepatitis B","volume":"52","author":"TT Chang","year":"2010","journal-title":"Hepatology"},{"key":"pone.0270716.ref003","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1136\/gutjnl-2012-302024","article-title":"Virological response to entecavir is associated with a better clinical outcome in chronic hepatitis B patients with cirrhosis","volume":"62","author":"R Zoutendijk","year":"2013","journal-title":"Gut"},{"key":"pone.0270716.ref004","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1002\/hep.26180","article-title":"Long-term entecavir treatment reduces hepatocellular carcinoma incidence in patients with hepatitis B virus infection","volume":"58","author":"T Hosaka","year":"2013","journal-title":"Hepatology"},{"key":"pone.0270716.ref005","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.jhep.2019.11.003","article-title":"Guidance for design and endpoints of clinical trials in chronic hepatitis B\u2014Report from the 2019 EASL-AASLD HBV Treatment Endpoints Conference(\u2021)","volume":"72","author":"M Cornberg","year":"2020","journal-title":"Journal of hepatology"},{"key":"pone.0270716.ref006","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1136\/gutjnl-2013-305517","article-title":"HBsAg seroclearance after nucleoside analogue therapy in patients with chronic hepatitis B: clinical outcomes and durability","volume":"63","author":"GA Kim","year":"2014","journal-title":"Gut"},{"key":"pone.0270716.ref007","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1053\/j.gastro.2008.07.008","article-title":"HBsAg Seroclearance in chronic hepatitis B in Asian patients: replicative level and risk of hepatocellular carcinoma","volume":"135","author":"MF Yuen","year":"2008","journal-title":"Gastroenterology"},{"key":"pone.0270716.ref008","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1002\/hep.29323","article-title":"Hepatitis B cure: From discovery to regulatory approval","volume":"66","author":"AS Lok","year":"2017","journal-title":"Hepatology"},{"key":"pone.0270716.ref009","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.jhep.2012.02.010","article-title":"EASL clinical practice guidelines: Management of chronic hepatitis B virus infection","volume":"57","year":"2012","journal-title":"Journal of hepatology"},{"key":"pone.0270716.ref010","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1053\/j.gastro.2008.05.031","article-title":"Sustained HBeAg and HBsAg loss after long-term follow-up of HBeAg-positive patients treated with peginterferon alpha-2b","volume":"135","author":"EH Buster","year":"2008","journal-title":"Gastroenterology"},{"key":"pone.0270716.ref011","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1007\/s12072-012-9343-x","article-title":"Hepatitis B surface antigen levels: association with 5-year response to peginterferon alfa-2a in hepatitis B e-antigen-negative patients","volume":"7","author":"P Marcellin","year":"2013","journal-title":"Hepatology international"},{"key":"pone.0270716.ref012","doi-asserted-by":"crossref","first-page":"2682","DOI":"10.1056\/NEJMoa043470","article-title":"Peginterferon Alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B","volume":"352","author":"GK Lau","year":"2005","journal-title":"The New England journal of medicine"},{"key":"pone.0270716.ref013","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1002\/hep.24555","article-title":"Shorter durations and lower doses of peginterferon alfa-2a are associated with inferior hepatitis B e antigen seroconversion rates in hepatitis B virus genotypes B or C","volume":"54","author":"YF Liaw","year":"2011","journal-title":"Hepatology"},{"key":"pone.0270716.ref014","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1007\/s12072-007-9022-5","article-title":"Sustained response to peginterferon alfa-2a (40 kD) with or without lamivudine in Asian patients with HBeAg-positive and HBeAg-negative chronic hepatitis B","volume":"2","author":"T Piratvisuth","year":"2008","journal-title":"Hepatology international"},{"key":"pone.0270716.ref015","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s11901-010-0041-7","article-title":"Pros and Cons of Peginterferon Versus Nucleos(t)ide Analogues for Treatment of Chronic Hepatitis B","volume":"9","author":"MJ Sonneveld","year":"2010","journal-title":"Current hepatitis reports"},{"key":"pone.0270716.ref016","doi-asserted-by":"crossref","first-page":"2727","DOI":"10.3748\/wjg.v27.i21.2727","article-title":"Toward a new era of hepatitis B virus therapeutics: The pursuit of a functional cure","volume":"27","author":"EP Tsounis","year":"2021","journal-title":"World journal of gastroenterology"},{"key":"pone.0270716.ref017","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S0140-6736(05)17701-0","article-title":"Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomised trial","volume":"365","author":"HL Janssen","year":"2005","journal-title":"Lancet"},{"key":"pone.0270716.ref018","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/j.jhep.2014.05.044","article-title":"Switching from entecavir to PegIFN alfa-2a in patients with HBeAg-positive chronic hepatitis B: a randomised open-label trial (OSST trial)","volume":"61","author":"Q Ning","year":"2014","journal-title":"Journal of hepatology"},{"key":"pone.0270716.ref019","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1111\/j.1365-2036.2011.04750.x","article-title":"Randomised clinical trial: efficacy of peginterferon alfa-2a in HBeAg positive chronic hepatitis B patients with lamivudine resistance","volume":"34","author":"J Sun","year":"2011","journal-title":"Alimentary pharmacology & therapeutics"},{"key":"pone.0270716.ref020","doi-asserted-by":"crossref","first-page":"4121","DOI":"10.1128\/AAC.00249-15","article-title":"Sequential combination therapy with pegylated interferon leads to loss of hepatitis B surface antigen and hepatitis B e antigen (HBeAg) seroconversion in HBeAg-positive chronic hepatitis B patients receiving long-term entecavir treatment","volume":"59","author":"GJ Li","year":"2015","journal-title":"Antimicrobial agents and chemotherapy"},{"key":"pone.0270716.ref021","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1002\/hep.23571","article-title":"Serum hepatitis B surface antigen and hepatitis B e antigen titers: disease phase influences correlation with viral load and intrahepatic hepatitis B virus markers","volume":"51","author":"AJ Thompson","year":"2010","journal-title":"Hepatology"},{"key":"pone.0270716.ref022","doi-asserted-by":"crossref","first-page":"816","DOI":"10.3346\/jkms.2005.20.5.816","article-title":"Hepatitis B virus genotype C prevails among chronic carriers of the virus in Korea","volume":"20","author":"SH Bae","year":"2005","journal-title":"Journal of Korean medical science"},{"key":"pone.0270716.ref023","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3851\/IMP1887","article-title":"Durable hepatitis B surface antigen decline in hepatitis B e antigen-positive chronic hepatitis B patients treated with pegylated interferon-\u03b12b: relation to response and HBV genotype","volume":"17","author":"MJ Sonneveld","year":"2012","journal-title":"Antiviral therapy"},{"key":"pone.0270716.ref024","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.jhep.2017.03.021","volume":"67","author":"EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection","year":"2017","journal-title":"Journal of hepatology"},{"key":"pone.0270716.ref025","doi-asserted-by":"crossref","first-page":"E1","DOI":"10.1002\/hep.24473","article-title":"Clinical utility of hepatitis B surface antigen quantitation in patients with chronic hepatitis B: a review","volume":"54","author":"YF Liaw","year":"2011","journal-title":"Hepatology"},{"key":"pone.0270716.ref026","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/S0016-5085(00)70261-7","article-title":"Hepatitis B genotypes correlate with clinical outcomes in patients with chronic hepatitis B","volume":"118","author":"JH Kao","year":"2000","journal-title":"Gastroenterology"},{"key":"pone.0270716.ref027","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1086\/314688","article-title":"Core promoter mutations and genotypes in relation to viral replication and liver damage in East Asian hepatitis B virus carriers","volume":"179","author":"M Lindh","year":"1999","journal-title":"The Journal of infectious diseases"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0270716","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T17:38:17Z","timestamp":1658511497000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0270716"}},"subtitle":[],"editor":[{"given":"Jee-Fu","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,7,22]]},"references-count":27,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,7,22]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0270716","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,22]]}}}