{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T13:31:25Z","timestamp":1789133485975,"version":"build-2803163510"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2022,3,14]],"date-time":"2022-03-14T00:00:00Z","timestamp":1647216000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2022,3,14]],"date-time":"2022-03-14T00:00:00Z","timestamp":1647216000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>Treatment of immune\u2010tolerant (IT) children and adults with combined peginterferon alfa\u20102a and entecavir results in a decline in serum HBeAg and HBsAg concentrations but rarely results in loss of HBeAg or sustained off\u2010treatment response. Factors associated with declines in these viral antigens during treatment remain unexplored.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>We investigated the pattern of virologic and biochemical response in 86 participants (59 children, 27 adults) by serial quantitative measurement of HBsAg (qHBsAg), quantitative HBeAg (qHBeAg), HBV RNA, interferon\u2010inducible protein (IP\u201010), IL\u201018, and alanine aminotransferase (ALT). Each individual had previously been treated with 8 weeks of entecavir followed by 40 weeks of combined peginteferon and entecavir. We defined the interrelationships between these parameters and virologic response measured as nadir declines from baseline for HBeAg and HBsAg. The patterns of HBsAg and HBeAg decline were similar in pediatric and adult participants. Higher levels of IP\u201010 were observed during treatment in participants with greater ALT elevations and greater reductions of qHBsAg and qHBeAg. Individuals with peak ALT values exceeding three times the upper limit of normal were significantly more likely to have &gt;1 log<jats:sub>10<\/jats:sub> decline in both viral antigens. HBV DNA became undetectable in 21 of 86 (24%) and HBV RNA in 4 of 77 (5%) during therapy, but both markers remained negative only in those who became HBsAg negative, all of whom also had ALT elevations.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Induction of IP\u201010 during peginterferon treatment in adults and children in the IT phase of chronic HBV infection is associated with ALT elevations and decline in viral antigens, suggesting a degree of interferon\u2010inducible viral control.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.32400","type":"journal-article","created":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T11:56:18Z","timestamp":1645444578000},"page":"775-787","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":17,"title":["Changes in serum hepatitis B surface and e antigen, interferon\u2010inducible protein 10, and aminotransferase levels during combination therapy of immune\u2010tolerant chronic hepatitis B"],"prefix":"10.1097","volume":"76","author":[{"given":"Robert","family":"Perrillo","sequence":"first","affiliation":[{"name":"Baylor Scott and White Medical Center,Dallas,Texas,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsing\u2010Hua S.","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Epidemiology,University of Pittsburgh,Pittsburgh,Pennsylvania,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen B.","family":"Schwarz","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine,Baltimore,Maryland,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Rosenthal","sequence":"additional","affiliation":[{"name":"University of California,San Francisco,California,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauricio","family":"Lisker\u2010Melman","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine,St. Louis,Missouri,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond T.","family":"Chung","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital,Boston,Massachusetts,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludmila","family":"Prokunina\u2010Olsson","sequence":"additional","affiliation":[{"name":"National Cancer Institute,Rockville,Maryland,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin","family":"Cloherty","sequence":"additional","affiliation":[{"name":"Abbott Diagnostics,Abbott Park,Illinois,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan","family":"Feld","sequence":"additional","affiliation":[{"name":"Toronto Centre for Liver Disease,University of Toronto University Health Network,Toronto,Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Hepatitis B Research Network (HBRN)","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2022,3,14]]},"reference":[{"issue":"6","key":"hep32400-bib-0001-20250824","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/S2468-1253(18)30056-6","article-title":"Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study","volume":"3","year":"2018","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"hep32400-bib-0002-20250824","first-page":"S82","article-title":"Hepatitis B virus 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