Abstract: Objective To investigate the risk factors for relapse after discontinuation of nucleos(t)ide analogues (NAs) in patients with chronic hepatitis B (CHB).Methods Electronic searches were conducted in PubMed, Cochrane Library, EMBASE and CBM before March 2018. A meta-analysis was performed based on the extracted data using Review Manager software (RevMan version 5.3). Results From 2002 to 2018, a total of 64 studies were included to investigate the correlation between candidate risk factors and virological relapse (VR). For each additional year of age, the risk of VR was relatively increased by 4%. For each additional month to complete virological response, the risk of VR was relatively increased by 13%. For each additional logarithmic level of hepatitis B surface antigen (HBsAg), the risk of VR was relatively increased by 81%. Interestingly, new markers such as Hepatitis B core-related antigen (HBcrAg), hepatitis B virus ribonucleic acid (HBV RNA) and quantitative detection of antibody to hepatitis B core antigen (anti-HBc) preliminarily indicated their predictive potential in VR. Conclusion The age of patients with chronic hepatitis B, the time required for virological response to antiviral treatment, and HBsAg level at the end of NAs treatment are positively correlated with VR. Predictive value for VR of new markers such as HBcrAg, HBV RNA and quantitative detection of anti-HBc remains to be further investigated and confirmed by extensive clinical studies.

Key words: Chronic hepatitis B, Nucleos(t)ide analogues, Virological relapse, Risk factor, meta-analysis