Kaneko S, Kurosaki M, Inada K, et al. - Researchers not only determined the virological features of hepatitis B core-related antigen (HBcrAg) in chronic hepatitis B (CHB) patients but also explored the hepatocellular carcinoma (HCC) risk factors of HBeAg-negative patients. This study included 245 naive CHB patients, in whom HBcrAg was recorded prior to receiving Nucleoside/nucleotide analogs (NA) therapy. HBeAg-positive patients had significantly higher median HBcrAg levels compared with HBeAg-negative patients. A 5-year cumulative HCC incidence rate of 5.4% was estimated in the HBeAg-negative cohort, during a median observation span of 5.28 (1.03–12.0) years. Multivariate Cox regression analysis demonstrated that HCC development in HBeAg-negative patients who underwent NA therapy and even in noncirrhosis patients was independently predicted by higher HBcrAg levels at 1 year. In the light of these data, experts concluded HBcrAg as beneficial in terms of understanding disease progression in CHB cases as well as for stratifying carcinogenesis risk in HBeAg-negative cases undergoing NA therapy.