{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T14:01:07Z","timestamp":1780581667018,"version":"3.54.1"},"reference-count":51,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2019,11,6]],"date-time":"2019-11-06T00:00:00Z","timestamp":1572998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Insulin resistance associated disorders (IRAD), including prediabetes, type 2 diabetes mellitus (T2DM), and fatty liver are significant risk factors of liver-related death in chronic hepatitis B (CHB). However, their relationship remains unclear. We aimed to evaluate how IRAD influence the kinetics of serum hepatitis B surface antigen (HBsAg) in patients with CHB during long-term entecavir treatment. We enrolled 140 patients with CHB receiving at least 3 years of consecutive entecavir treatment in this retrospective study. A linear mixed effects model was adopted to examine the effects of variables and their interaction over time on the HBsAg trajectory. Furthermore, we acquired cytokine profiles and baseline fibrosis-4 index (FIB-4) scores for in-depth analysis. The median treatment time was 6.90 (4.47\u20139.01) years. Multivariate analysis revealed that older patients or those with prediabetes or T2DM had a significantly slower HBsAg decline over time (p = 0.0001 and p &lt; 0.0001, respectively). Conversely, advanced fatty liver engendered a more rapid HBsAg decrease (p = 0.001). Patients with prediabetes or T2DM possessed higher IP-10 levels six years after entecavir therapy (p = 0.013). Compared to patients without prediabetes or T2DM, diabetic patients had more unfavorable features at the baseline, especially higher FIB-4 scores. Prediabetes or T2DM delays the clearance of HBsAg, but advanced hepatic fatty change counterbalances the effect. Additionally, IRAD could cause hepatic sequelae in CHB through immune-metabolic pathways.<\/jats:p>","DOI":"10.3390\/jcm8111892","type":"journal-article","created":{"date-parts":[[2019,11,7]],"date-time":"2019-11-07T06:52:36Z","timestamp":1573109556000},"page":"1892","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Insulin Resistance Associated Disorders Pivoting Long-Term Hepatitis B Surface Antigen Decline During Entecavir Therapy"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7708-5589","authenticated-orcid":false,"given":"Tien-Ching","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan"},{"name":"Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Chun","family":"Liu","sequence":"additional","affiliation":[{"name":"Infectious Disease and Signaling Research Center, National Cheng Kung University, Tainan 701, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2738-2638","authenticated-orcid":false,"given":"Yu-Hsiang","family":"Hsu","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan"},{"name":"Clinical Medicine Research Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Jhen","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen-Cheng","family":"Chiu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9538-7188","authenticated-orcid":false,"given":"Hung-Chih","family":"Chiu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pin-Nan","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5418-8315","authenticated-orcid":false,"given":"Chiung-Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-Tsung","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan"},{"name":"Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan"},{"name":"Infectious Disease and Signaling Research Center, National Cheng Kung University, Tainan 701, Taiwan"},{"name":"Clinical Medicine Research Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8280-5133","authenticated-orcid":false,"given":"I-Chin","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan"},{"name":"Infectious Disease and Signaling Research Center, National Cheng Kung University, Tainan 701, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.jhep.2017.03.021","article-title":"EASL 2017 clinical practice guidelines on the management of hepatitis B virus infection","volume":"67","author":"Lampertico","year":"2017","journal-title":"J. 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