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Although upsurge of viral load always precedes or coincides with AE<\/jats:styled-content>, the underlying immunological mechanisms remain unclear and were investigated.<\/jats:p><\/jats:sec>Methods<\/jats:title>We prospectively followed the serum cytokine\/chemokine profiles, viral load, and alanine aminotransferase (ALT<\/jats:styled-content>) levels in 250 patients and identified 44 consecutive patients (male: 72.7%; age: 40.4\u2009\u00b1\u20099.7 years; hepatitis B e antigen [HBeAg<\/jats:styled-content>] positivity: 63.6%; genotype B<\/jats:styled-content>\/C<\/jats:styled-content>: 75%\/25%) who developed AE<\/jats:styled-content> during the follow\u2010up in a medical center. The impact of clinical characteristics (age, gender, HBeAg<\/jats:styled-content>, ALT<\/jats:styled-content>, HBV<\/jats:styled-content> genotype), cytokines (tumor necrosis factor\u2010alpha, interferon gamma, interleukin [IL<\/jats:styled-content>]\u20102, IL<\/jats:styled-content>\u20104, IL<\/jats:styled-content>\u20106, and IL<\/jats:styled-content>\u201010), and chemokines (CXCL<\/jats:styled-content>10\/interferon gamma\u2010induced protein [IP<\/jats:styled-content>]\u201010, CCL<\/jats:styled-content>2\/MCP<\/jats:styled-content>\u20101, CXCL<\/jats:styled-content>9\/MIG<\/jats:styled-content>, CCL<\/jats:styled-content>5\/RANTES<\/jats:styled-content>, and CXCL<\/jats:styled-content>8\/IL<\/jats:styled-content>\u20108) on the serum HBV DNA<\/jats:styled-content> dynamics at different time points (baseline, peak of serum HBV DNA<\/jats:styled-content> level, peak of serum ALT<\/jats:styled-content> level, and after AE<\/jats:styled-content>) were analyzed.<\/jats:p><\/jats:sec>Results<\/jats:title>Of 44 patients, serum HBV DNA<\/jats:styled-content> level surged before the peak of serum ALT<\/jats:styled-content> level in 23 (52.3%), and coincided with the peak of ALT<\/jats:styled-content> in 21 (47.7%). The upsurge of serum viral load significantly correlated with the increase of IL<\/jats:styled-content>\u201010 (P<\/jats:italic>\u2009=\u20090.0037) and CXCL<\/jats:styled-content>10\/IP<\/jats:styled-content>\u201010 (P<\/jats:italic>\u2009=\u20090.0044). Upsurge of serum viral load was preceded by an increase in serum IL<\/jats:styled-content>\u20104 (P<\/jats:italic>\u2009<\u20090.05), IL<\/jats:styled-content>\u20106 (P<\/jats:italic>\u2009<\u20090.05), and IL<\/jats:styled-content>\u201010 (P<\/jats:italic>\u2009<\u20090.05). Combination of HBV<\/jats:styled-content> genotype, IL<\/jats:styled-content>\u20106 level at baseline, and ALT<\/jats:styled-content> level at the peak of serum HBV DNA<\/jats:styled-content> reliably predicted subsequent AE<\/jats:styled-content> pattern (P<\/jats:italic>\u2009=\u20090.0116).<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Enhanced T<\/jats:styled-content>h2 activity is likely involved in the surge of HBV DNA<\/jats:styled-content> level before hepatitis exacerbation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jgh.12606","type":"journal-article","created":{"date-parts":[[2014,4,15]],"date-time":"2014-04-15T09:06:45Z","timestamp":1397552805000},"page":"1629-1636","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Serum cytokine\/chemokine profiles in acute exacerbation of chronic hepatitis B<\/scp>: Clinical and mechanistic implications"],"prefix":"10.1111","volume":"29","author":[{"given":"Hui\u2010Lin","family":"Wu","sequence":"first","affiliation":[{"name":"Graduate Institute of Clinical Medicine National Taiwan University College of Medicine and National Taiwan University Hospital Taipei Taiwan"},{"name":"Hepatitis Research Center National Taiwan University College of Medicine and National Taiwan University Hospital Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia\u2010Horng","family":"Kao","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Medicine National Taiwan University College of Medicine and National Taiwan University Hospital Taipei Taiwan"},{"name":"Department of Internal Medicine National Taiwan University College of Medicine and National Taiwan University Hospital Taipei Taiwan"},{"name":"Hepatitis Research Center National Taiwan University College of Medicine and National Taiwan University Hospital Taipei Taiwan"},{"name":"Department of Medical Research National Taiwan University College of Medicine and National Taiwan University Hospital Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting\u2010Chih","family":"Chen","sequence":"additional","affiliation":[{"name":"Hepatitis Research Center National Taiwan University College of Medicine and National Taiwan University Hospital Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010Hsuan","family":"Wu","sequence":"additional","affiliation":[{"name":"Hepatitis Research Center National Taiwan University College of Medicine and National Taiwan University Hospital Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen\u2010Hua","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine National Taiwan University College of Medicine and National Taiwan University Hospital Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tung\u2010Hung","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine National Taiwan University College of Medicine and National Taiwan University Hospital Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung\u2010Chih","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine National Taiwan University College of Medicine and National Taiwan University Hospital Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ding\u2010Shinn","family":"Chen","sequence":"additional","affiliation":[{"name":"Distinguished Visiting Fellow Genomics Research Center Academia Sinica Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei\u2010Jer","family":"Chen","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Medicine National Taiwan 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