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Serum hepatitis B core antibody levels predict HBeAg seroconversion in chronic hepatitis B patients with high viral load treated with nucleos(t)ide analogs

Authors Cai S, Li Z, Yu T, Xia M, Peng J

Received 18 January 2018

Accepted for publication 19 February 2018

Published 3 April 2018 Volume 2018:11 Pages 469—477


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 2

Editor who approved publication: Professor Suresh Antony

Shaohang Cai,* Zhandong Li,* Tao Yu, Muye Xia, Jie Peng

Department of Infectious Diseases and Hepatology Unit, NanFang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China

*These authors contributed equally to this work

Patients with chronic hepatitis B virus (HBV) infection who are hepatitis B virus e antigen (HBeAg) positive are increasingly being treated with nucleos(t)ide analogs (NUCs). However, the predictive value of serum hepatitis B virus core antibody (HBcAb) levels for HBeAg seroconversion among patients with high viral load remains unclear. 
Methods: This study consisted of 74 patients with high viral load (HBV DNA >1 × 107 copies/mL) enrolled in a multicenter, randomized, controlled trial, treated with lamivudine and adefovir (N = 32) or entecavir (N = 42) for up to 96 weeks. Serum HBV DNA, quantitative hepatitis B virus surface antigen (HBsAg), HBeAg, and HBeAb was tested at each visit. Quantitative HBcAb evaluation was conducted for all the available samples in the trial, by using a newly developed double-sandwich anti-HBc immunoassay.
Results: Serum HBcAb levels were significantly higher in patients with a serum alanine aminotransferase (ALT) level more than five times the upper limit of normal (ULN) compared with patients with ALT levels within 5 × ULN (4.25 ± 0.61 vs. 3.94 ± 0.47 log10 IU/mL, P = 0.0345). Patients with HBeAg seroconversion were associated with a higher level of HBcAb at baseline, compared with those without HBeAg seroconversion (4.38 ± 0.54 vs. 4.02 ± 0.58 log10 IU/mL, = 0.029). The area under receiver operating characteristic curve of baseline HBcAb for HBeAg seroconversion was 0.71 (95% CI: 0.55–0.86, P = 0.013). When the baseline HBcAb level was >4.375 log10 IU/mL, the sensitivity and specificity to predict HBeAg seroconversion at week 96 were 62.5% and 74.2%, and the positive likelihood ratio (LR) and negative LR were 2.42 and 0.51, respectively. The multivariate analysis result indicated that baseline serum HBcAb level was the only independent predictor for HBeAg seroconversion at week 96, with an odds ratio of 4.78.
Conclusion: Baseline serum HBcAb level >4.375 log10 IU/mL could satisfactorily predict HBeAg seroconversion among patients with high viral load treated with NUC.
Keywords: chronic hepatitis B, HBV: hepatitis B core antibody, hepatitis B e antigen, seroconversion, high viral load

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