Hepatitis B Core-Related Antigen is a Biomarker for off-Treatment Relapse After Long-Term Nucleos(t)ide Analog Therapy in Patients with Chronic Hepatitis B

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. 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. 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, = 0.005) and age (HR = 1.051, 95% CI: 1.010-1.093, = 0.049) were independently associated with clinical relapse. A cut-off value of 4.0 log U/mL of HBcrAg was defined by maximized Youden's index. An EOT HBcrAg level of ≥4.0 log U/mL was associated with higher risks of clinical relapse (65.8% vs 23.2%,