Table 2.

Novel biomarkers for clinical monitoring in CHB.

Biomarker	Clinical application	Research evidence	Mechanism/characteristics
Serum HBV RNA	1. Predict HBeAg seroconversion and virological response in NAs-treated patients 2. Evaluate HBeAg seroconversion efficacy in Peg-IFNα therapy 3. Non-invasively reflect transcriptional activity of intrahepatic cccDNA 4. A pretreatment level of <4.12 log10 copies/mL is an effective predictor of HBeAg seroconversion 5. Week 12 levels predict HBeAg seroconversion and virological response at week 96	(Jia et al., 2019; Luo et al., 2019; Ji et al., 2020; Wang et al., 2021; Wang et al., 2022; Kosaka et al., 2025)	- Low levels indicate reduced cccDNA quantity or transcriptional suppression - Stronger correlation with intrahepatic cccDNA than HBcrAg, HBV DNA, etc.
HBcrAg	1. Assess viral replication and transcriptional activity during NAs therapy 2. Predict treatment outcomes (e.g., HBeAg seroconversion, HBsAg clearance)	(Lee HW. et al., 2021; Sandmann et al., 2024)	- Composed of HBV core-related proteins; reflects cccDNA activity and nucleocapsid assembly/release - Requires combined detection with traditional markers
qAnti-HBc	1. Predict HBeAg seroconversion efficacy in Peg-IFNα or NAs therapy 2. Evaluate host immune response intensity to HBV	(Hou et al., 2015; Fan et al., 2016; Shi et al., 2023; Lazarevic et al., 2024)	- Baseline >4.4 log IU/mL associated with higher seroconversion rates - Reflects hepatitis activity and liver pathological changes