Quantitative hepatitis B core antibody and quantitative hepatitis B surface antigen: Novel viral biomarkers for chronic hepatitis B management

Table 1 Summary of the incidence of hepatocellular carcinoma, hepatic decompensation, and hepatitis B surface antigen seroreversion of chronic hepatitis B patients with hepatitis B surface antigen seroclearance

Ref.	Country/region	Study design	n	HBsAg seroreversion (%)	Hepatic decompensation (%)	HCC incidence (%)
Spontaneous HBsAg seroclearance
Yip et al[43], 2023	Hong Kong	Retrospective	7942	6.1	1.3	1.1
Yip et al[44], 2021	Hong Kong	Retrospective	5917	7	-	1.6
Choi et al[45], 2021	South Korea	Retrospective	1624	1.2	-	2.2
Park et al[46], 2021	South Korea	Retrospective	984	-	10.9	1.4
Yeo et al[47], 2020	Multicenter	Retrospective	11264	1.3	-	-
Song et al[48], 2019	China	Prospective	652	-	-	1.2
Zhu et al[49], 2018	China	Prospective	348	-	-	0.2
Chen et al[50], 2016	Taiwan	Retrospective	312	-	-	1.3
NAs treatment HBsAg seroclearance
Yip et al[44], 2021	Hong Kong	Retrospective	1207	7.7	-	1.3
Choi et al[45], 2021	South Korea	Retrospective	348	5.5	-	4
Kim et al[51], 2020	South Korea	Retrospective	276	3.6	-	2.9
Yip et al[52], 2019	Hong Kong	Retrospective	376	1.4	-	0.5
Suarez et al[53], 2019	Spain	Retrospective	69	1.5	-	1.5
Sun et al[54], 2019	China	Retrospective	54	-	-	0
Chi et al[55], 2017	Multicenter	Retrospective	70	3.7	-	0
Chen et al[50], 2016	Taiwan	Retrospective	110	-	-	0.9
IFN-α alone or combined with NAs treatment HBsAg seroclearance
Li et al[56], 2022	China	Prospective	231	8.2	-	-
Chen et al[57], 2021	China	Prospective	48	6.3	-	0
Wu et al[58], 2021	China	Prospective	68	-	-	0
Pan et al[59], 2021	China	Prospective	376	17.3	-	0.3
Wu et al[60], 2020	China	Retrospective	238	5.9	-	0
Choi et al[61], 2020	Canada	Retrospective	65	1.9	-	4.4
Li et al[62], 2019	China	Prospective	176	13.4	-	0.6

CHB: Chronic hepatitis B; HBsAg: Hepatitis B surface antigen; HCC: Hepatocellular carcinoma; INF-α: Interferon-alpha; NAs: Nucleoside analogues.

Table 2 Summary of the characteristics of quantitative hepatitis B surface antigen assays from several companies

Test names	Companies	Principle techniques	Detection methods	Pretreatment procedure	Range of detection	On-board dilution
Elecsys HBsAg II	Roche Diagnostic	Sandwich technique, 2 capture mAbs, and a mixture of mAbs and polyAbs detection	ECLIA (ruthenium)	None	0.05–130 IU/mL	1:400 with buffered negative human serum
Architect HBsAg QT	Abbott Laboratories	Sandwich technique, capture mAbs, and polyAbs detection	CMIA (acridinium)	None	0.05–250 IU/mL	1:500 with recalcified negative human plasma
Sysmex HISCL HBsAg	Sysmex Corporation	Sandwich technique, capture mAbs, and mAbs detection	CLEIA (CDP-Star)	None	0.03–2500 IU/mL	Auto dilution
Lumipulse G HBsAg-Quant	Fujirebio Incorporation	Sandwich technique, 2 capture mAbs and 2 detections mAbs	CLEIA (AMPPD)	Yes, to disrupt viral particles and dissociate HBsAg from HBsAg-anti-HBs complexes	0.005–150 IU/mL	1:100, 1:200 or 1:1000 with NaCl and Tris buffer
iTACT-HBsAg	Fujirebio Incorporation	Sandwich technique	ICT-CLEIA (AMPPD)	Yes, to inactivate anti-HBs, releases the antigen from the immune complexes, and to disassociate the antigen polymers into monomers	0.0005–113 IU/mL	N/A

AMPPD: Adamantane; CMIA: Chemiluminescent microparticle immunoassay; CLEIA: Chemiluminescent enzyme immunoassay; ECLIA: Electrochemiluminescence immunoassay; ICT-CLEIA: Immune complex transfer-chemiluminescent enzyme immunoassay; iTACT: Immunoassay for total antigen including complex via pretreatment; mAbs: Monoclonal antibodies; polyAbs: Polyclonal antibodies; N/A: Not associated.

Table 3 Summary of the characteristics of quantitative hepatitis B antibody assays from several companies

Test names	Companies	Principle techniques	Detection methods	Range of detection
Anti-HBc QN[93]	Wantai BioPharm	Double-antigen sandwich	ELISA	0.1–25 IU/mL
Anti-HBc HQ[94]	United Medical Instruments	Fully automated two-step sandwich	CMIA	100–100000 IU/mL
Lumipulse G HBcAb-N[95]	Fujirebio Incorporation	Fully automated two-step sandwich	CLEIA	0.5–50 IU/mL
Europium III chelate microparticles HBcAb[96]	Guangzhou Darui Biotechnology	Rapid fluorescence POCT	LFIA	0-640 IU/mL

CLEIA: Chemiluminescent enzyme immunoassay; CMIA: Chemiluminescent microparticle immunoassay; ELISA: Enzyme-linked immunosorbent assay; HBcAb: Hepatitis B core antibody; HQ: High value quantitative detection; LFIA: Lateral flow immunoassay; POCT: Point-of-care test; QN: General value quantitative detection.