Virological and Immunological Characteristics of HBeAg-Positive Chronic Hepatitis B Patients With Low HBsAg Levels

HBeAg-positive chronic hepatitis B (CHB) with low HBsAg levels represents a relatively rare serological pattern and is closely associated with the severity of liver disease. However, the underlying mechanisms in such cases remain largely unclear.

Treatment-naïve HBeAg-positive CHB patients with low HBsAg levels in China were enrolled and analysed. In vitro cell experiments and immunoassays were conducted to investigate the effects of the preS2 deletion mutation on virus reproduction and host immune response.

Treatment-naïve HBeAg-positive CHB patients with low HBsAg levels (low HBsAg group) exhibited higher fibrosis scores and a greater prevalence of quasispecies mutations introduced by preS2 deletion compared to patients with positive HBeAg and high HBsAg levels (high HBsAg group). Further analysis revealed that fibrosis scores in CHB patients with the preS2 deletion mutations were significantly higher compared to both in wild-type patients and the high HBsAg group. In vitro assays indicated that while this mutation may not impact HBV replication, it significantly reduced viral infectivity. The number of viral-specific IFN-γ-secreting cells induced by the mutant was significantly lower than that induced by the wild-type strain. Additionally, the levels of HBs-specific B cells and cytokine secretion from lymphocytes triggered by the mutant strain were significantly reduced.

HBeAg-positive CHB patients with low HBsAg and genotype C exhibited higher noninvasive fibrosis indexes compared with typical patients, accompanied by a significant increase in quasispecies variants associated with preS2 deletion. The emergence of the preS2 deletion mutants in patients could be due to its enhanced ability to evade the host immunity.