Table 1.

Clinical applications of HBcrAg in CHB patients

Category	Finding	HBcrAg level (log U/mL) and point	Reference
Natural history	HBeAg seroconversion	<4.92 log U/mL during the clinical course	[37]
	HBsAg seroclearance	Undetectable (79%), 2.7 log U/mL (median of 21%) during the clinical course	[37,48]
cccDNA activity	Lower amounts of intrahepatic cccDNA and lower cccDNA activity	<3 log U/mL	[38]
	Identification of inactive carriers with a high accuracy (any HBV genotype)	HBcrAg ≤3 log U/mL plus HBV DNA ≤2,000 IU/mL	[39]
Anti-HBV treatment	HBeAg seroconversion by PEG-IFN at 12 weeks	>8 log U/mL (no response) at the beginning of therapy	[49]
	HBeAg seroconversion by PEG-IFN plus NA for 4 weeks followed by PEG-IFN for 20 weeks	>4.5 log U/mL (no response) at the beginning of therapy	[140]
	No LAM resistance	<4.6 log U/mL at 6 months of treatment	[141]
	Virological relapse within 1 year of NA cessation	>3.7 log U/mL at NA cessation	[56]
	Virological relapse regardless of undetectable HBV DNA for at least 6 months	3.2-3.7 log U/mL at NA (LAM or ETV) cessation	[53,54]
HCC occurrence/recurrence	At high risk for HCC with intermediate viral load (HBV DNA 2,000-19,999 U/mL)	≥4.0 log U/mL	[65]
	Cumulative incidence of HCC during NA treatment	≥3.4 log U/mL at the time of HBV DNA disappearance	[56]
	HCC development during NA treatment	Detectable HBcrAg during NA treatment	[63]
	Long-term effect of NA treatment on HCC progression	Higher serum levels of HBcrAg and BCP mutations were associated with progression to HCC, independent of NA therapy	[62]
	Evaluation of HCC occurrence	HBcrAg >3.0 log U/mL and HBsAg >3.0 log IU/mL (cut-off values)	[67]
	Incidence of HCC for treatment-experienced patients	>4.67 log U/mL at pre-treatment, >3.89 log U/mL at post-treatment	[66]
	HCC development during NA treatment	Detectable HBcrAg during NA treatment	[63]
	Incidence of HCC for treatment-naïve patients	>2.9 log U/mL during follow-up period	[61,64]
	HCC recurrence within 2 years	>4.8 log U/mL at time of HCC diagnosis	[61,64]
HBV reactivation	HBV reactivation by high-risk immunosuppressive therapy within 2 years	Detectable HBcrAg at baseline	[142]
HBV reinfection	High levels of post-liver transplantation cccDNA	>4 log U/mL before liver transplantation	[143]

HBcrAg, hepatitis B core-related antigen; CHB, chronic hepatitis B; HBeAg, hepatitis B envelope antigen; HBsAg, hepatitis B surface antigen; cccDNA, covalently closed circular DNA; HBV, hepatitis B virus; PEG-IFN, pegylated interferon; NA, nucleos(t)ide analogue; LAM, lamivudine; ETV, entecavir; HCC, hepatocellular carcinoma; BCP, basal core promoter.