HBcrAg and cirB‐RNA Do Not Predict Clinical and Virological Outcomes in Patients With HBeAg‐Negative Chronic Infection

Background & Aims: Predicting clinical and virological outcomes in HBeAg-negative (HBeAg-neg) chronic infection often requires long-term monitoring. Our study explored whether a single measurement of quantitative HBsAg (qHBsAg), HBV core-related antigen (HBcrAg), and circulating HBV RNA (cirB-RNA) can define the natural course of untreated HBeAg-neg chronic infection patients. Methods: To this aim, we included 128 naïve HBeAg-neg chronic infection patients, stratified according to qHBsAg levels in: (1) 10–1000 IU/mL, (2) 1000–10 000 IU/mL, and (3) > 10 000 IU/mL. Results: HBcrAg and cirB-RNA were detected in 27% and 19% of patients with qHBsAg > 1000 IU/mL but rarely detected in patients with qHBsAg < 1000 IU/mL. After a median follow-up of 5.1 years, 9.4% of patients lost HBsAg, and 8.5% experienced an increase in HBV DNA > 2000 IU/mL. qHBsAg < 1000 IU/mL was the only factor independently associated with functional cure. Conclusions: In untreated HBeAg-neg chronic infection patients, single-point cirB-RNA and HBcrAg do not offer additional predictive value over qHBsAg < 1000 IU/mL for spontaneous HBsAg loss.