The role of hepatitis B core-related antigen in predicting the occurrence and recurrence of hepatocellular carcinoma in patients with chronic hepatitis B: a systemic review and meta-analysis

Abstract Background The purpose of the current study was to investigate the predictive value of hepatitis B core-related antigen (HBcrAg) on the occurrence and recurrence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). Methods Based on PubMed, Embase, Scopus, and Web of Science, we conducted a systematic review and meta-analysis of original clinical literature. The primary outcomes were the occurrence and recurrence of HCC assessed by the hazard ratio (HR) or odds ratio (OR) with 95% confidence interval (CI). Results A total of 18 publications with 9039 CHB patients were included in the preliminary analysis. The pooled results suggest that HBcrAg positivity (adjusted HR = 3.10, 95%CI: 2.07–4.64, P < 0.001, I 2 = 62.4%, P = 0.021; OR = 5.65, 95%CI: 3.44–5.82, P < 0.001, I 2 = 0.00%, P = 0.42) was an independent risk factor for the occurrence of HCC. Further subgroup analysis revealed that 4.0 logU/ml may be the optimal cut-off value for HBcrAg to predict the occurrence of HCC. Our meta-analysis also suggests that HBcrAg is a predictor of HCC recurrence during antiviral therapy (adjusted HR = 1.71, 95%CI: 1.26–2.32; I 2 = 78.6%, P = 0.031) and is closely related to recurrence-free survival (RFS) after curative treatment of HCC (P = 0.001). Conclusion For patients with CHB, serum HBcrAg level is closely associated with the occurrence of HCC, regardless of whether nucleoside/nucleotide analogues (NAs) are administered, may also serve as a novel prognostic biomarker of recurrence in HCC. Confirmation of these findings requires more research.