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Open AccessArticle

Insulin Resistance Associated Disorders Pivoting Long-Term Hepatitis B Surface Antigen Decline During Entecavir Therapy

1
Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan
2
Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan
3
Infectious Disease and Signaling Research Center, National Cheng Kung University, Tainan 701, Taiwan
4
Clinical Medicine Research Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2019, 8(11), 1892; https://doi.org/10.3390/jcm8111892
Received: 23 September 2019 / Revised: 22 October 2019 / Accepted: 4 November 2019 / Published: 6 November 2019
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 (4.47–9.01) 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 < 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.
Keywords: chronic hepatitis B; nucleos(t)ide analogs; diabetes mellitus; fatty liver disease chronic hepatitis B; nucleos(t)ide analogs; diabetes mellitus; fatty liver disease
MDPI and ACS Style

Lin, T.-C.; Liu, W.-C.; Hsu, Y.-H.; Lin, J.-J.; Chiu, Y.-C.; Chiu, H.-C.; Cheng, P.-N.; Chen, C.-Y.; Chang, T.-T.; Wu, I.-C. Insulin Resistance Associated Disorders Pivoting Long-Term Hepatitis B Surface Antigen Decline During Entecavir Therapy. J. Clin. Med. 2019, 8, 1892.

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