Early Serum HBsAg Kinetics as Predictor of HBsAg Loss in Patients with HBeAg-Negative Chronic Hepatitis B after Treatmen
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RESEARCH ARTICLE
Early Serum HBsAg Kinetics as Predictor of HBsAg Loss in Patients with HBeAg-Negative Chronic Hepatitis B after Treatment with Pegylated Interferona-2a Minghui Li1,2 • Lu Zhang1 • Yao Lu1 • Qiqi Chen2 • Huihui Lu1 • Fangfang Sun1 • Zhan Zeng2 Gang Wan3 • Linqing Zhao4 • Yao Xie1,2
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Received: 19 January 2020 / Accepted: 16 July 2020 Ó Wuhan Institute of Virology, CAS 2020
Abstract Hepatitis B surface antigen (HBsAg) loss is an ideal treatment endpoint for patients with chronic hepatitis B (CHB). We investigated the predictive value of on-treatment HBsAg levels for HBsAg loss in hepatitis B e antigen (HBeAg)-negative CHB patients who received 120-week PEG-IFNa-2a treatment. Serum HBV DNA, HBsAg, and anti-HBs levels were assayed at baseline and every 3 months during the treatment. Of 81 patients, 12 achieved HBsAg loss, 20 achieved HBsAg \ 100 IU/mL, and 49 maintained HBsAg C 100 IU/mL. HBsAg loss rate was only 3.7% at 48 weeks, while it reached to 11.1% and 14.8% after treatment of 96 weeks and 120 weeks. The cutoff HBsAg levels at 12 weeks predicting HBsAg loss at 96 weeks and 120 weeks of treatment were 400 IU/mL and 750 IU/mL, with AUC 0.725 and 0.722, positive predictive value (PPV) 29.41% and 30.56%, and negative predictive value (NPV) 93.75% and 97.78%, respectively. The cutoff HBsAg levels at 24 weeks predicting HBsAg loss at 96 weeks and 120 weeks of treatment were 174 IU/mL and 236 IU/mL respectively, with AUC 0.925 and 0.922, PPV 40.0% and 46.15%, and both NPV 100%. The predictive ability of the cutoff HBsAg levels at 24 weeks was better than that at 12 weeks for HBsAg loss at either 96 or 120 weeks (v2 = 3.880, P = 0.049 and v2 = 4.412, P = 0.036). These results indicate that extended therapy is critical to HBsAg loss in HBeAg-negative CHB patients during PEG-IFN treatment, and the HBsAg level at 24 weeks can be used to predict HBsAg loss during tailoring PEG-IFN therapy. Keywords Chronic hepatitis B (CHB) Hepatitis B surface antigen (HBsAg) Pegylated interferon HBsAg loss HBeAg negative
Introduction
Minghui Li and Lu Zhang have contributed equally to this work. & Yao Xie [email protected] & Linqing Zhao [email protected] 1
Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
2
Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing 100015, China
3
Department of Biostatistics, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
4
Laboratory of Virology Capital Institute of Pediatrics, Beijing 100020, China
Hepatitis B virus (HBV) replication and detectable serum HBV DNA are closely associated with the progression of liver disease, liver decompensation, and occurrence of liver cirrhosis and hepatocellular carcinoma in patients with chronic hepatitis B (CHB) (Chen et al. 2006; Seto et al. 2018). Antiviral therapy is the most important and effective treatment to slow di
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