| Summary: | Guichan Liao,1,2 Xia Ding,1,2 Muye Xia,1,2 Yin Wu,1– 3 Hongjie Chen,1,2 Rong Fan,1,2 Xiaoyong Zhang,1,2 Shaohang Cai,1,2 Jie Peng1,2 1Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Guangzhou, People’s Republic of China; 3Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of ChinaCorrespondence: Jie Peng; Shaohang CaiDepartment of Infectious Diseases, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, Guangdong Province, People’s Republic of ChinaTel +86 020 6278 7428Fax +86 020 8771 9653Email pjie138@163.com; shaohangcai@foxmail.comObjective: It remains unknown how to stratify the risk of clinical relapse of chronic hepatitis B (CHB) patients after stopping nucleos(t)ide analogs (NAs) antiviral therapy.Methods: The current post hoc analysis included 122 non-cirrhotic patients with chronic hepatitis B virus infection who were positive for hepatitis B envelope antigen (HBeAg) and discontinued long-term NA therapy after achieving HBeAg seroconversion for a median of 2.5 years. Post hoc analysis of end-of-treatment (EOT) hepatitis B core-related antigen (HBcrAg) levels was performed using a chemiluminescent enzyme immunoassay.Results: A total of 78/122 (63.9%) patients experienced sustained response after NAs cessation, and 44/122 (36.1%) patients experienced clinical relapse. In multivariate analysis, EOT HBcrAg (hazard ratio [HR] = 2.105 95% CI: 1.440– 3.077, p < 0.001), hepatitis B surface antigen (HBsAg) ≥ 100 IU/mL (HR = 4.406, 95% CI 1.567– 12.389, p = 0.005) and age (HR = 1.051, 95% CI: 1.010– 1.093, p = 0.049) were independently associated with clinical relapse. A cut-off value of 4.0 log10 U/mL of HBcrAg was defined by maximized Youden’s index. An EOT HBcrAg level of ≥ 4.0 log10 U/mL was associated with higher risks of clinical relapse (65.8% vs 23.2%, p< 0.001) and HBeAg reversion (27.5% vs 1.6%, p < 0.001). In majority of patients (n = 91) who had a high EOT HBsAg level (≥ 100 IU/mL), serum HBcrAg level could further discriminate patients at low risk of clinical relapse. Patients with an HBcrAg level ≥ 4.0 log10 U/mL had significantly higher cumulative incidence rates of clinical relapse (78.1% vs 29.4%, p < 0.001) and HBeAg reversion (29.4% vs 0%, p < 0.001).Conclusion: Serum EOT HBcrAg level can be a predictor of off-treatment relapse in patients with CHB. An HBcrAg level of 4.0 log10 U/mL may identify patients at high risk of clinical relapse after treatment cessation.Keywords: chronic hepatitis B, discontinuation, hepatitis B core-related antigen, hepatitis B surface antigen
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