Quantification of HBsAg: Basic virology for clinical practice

Table 1 Recent clinical studies with quantification of hepatitis B surface antigen titers in hepatitis B virus infection

Author	Antiviral therapy	Correlation	Prediction	Clinical results
Deguchi et al[23]	-	HBV DNA	-	qHBsAg is higher in HBeAg(+)
Chen et al[28]	-	HBV DNA	-	qHBsAg is higher in HBeAg(+) and high HBV DNA levels, whereas qHBsAg is low in low HBV DNA level CHB
Werle-Lapostolle et al[29]	ADV	cccDNA, HBV DNA	-	HBsAg and cccDNA decrease with ADV
Kohmoto et al[30]	LAM	HBV DNA	-	qHBsAg is helpful for early detection of drug resistant strains
Wursthorn et al[35]	Peg-IFN + ADV	cccDNA	-	Peg-IFN + ADV decreases cccDNA and HBsAg, which are well correlated
Chan et al[36]	Peg-IFN + LAM	cccDNA	Low baseline qHBsAg can predict SVR	Peg-IFN + LAM decreases cccDNA and HBsAg, which are well correlated
Manesis et al[31]	IFN vs LAM	HBV DNA	Low baseline qHBsAg can predict SVR	IFN induces sharper decrease in qHBsAg than LAM
Wiegand et al[27]	FAM ± LAM	HBV DNA (not correlated)	Decline of qHBsAg can predict HBsAg loss	2 log drop to below 100 IU/mL is associated with HBsAg clearance
Moucari et al[32]	Peg-IFN	HBV DNA	Early qHBsAg drop can predict SVR	qHBsAg may be useful to optimize Peg-IFN therapy
Brunetto et al[33]	Peg-IFN ± LAM vs LAM	HBV DNA	On-treatment qHBsAg decline can predict sustained HBsAg loss	qHBsAg < 10 IU/mL at week 48 and 1 log decline predict sustained HBsAg clearance to optimize treatment strategy
Lau et al[37]	Peg-IFN ± LAM	-	On-treatment qHBsAg can be used as an early predictor of SVR	In HBeAg(+) patients, qHBsAg reduction through weeks 12, 24 and 48 were higher in patients with HBeAg seroconversion
Marcellin et al[38]	Peg-IFN ± LAM	-	qHBsAg at week 12 can predict long-term HBsAg clearance	35% of patients who had qHBsAg < 1500 IU/mL at week 12 cleared up HBsAg by 4 yr post-treatment
Lu et al[39]	Peg-IFN ± LAM	cccDNA	qHBsAg was superior to cccDNA and serum HBV DNA in predicting SVR	Area under ROC curve with qHBsAg, cccDNA and HBV DNA was 0.769, 0.734, and 0.714, respectively, for predicting SVR
Brunetto et al[65]	Peg-IFN ± LAM	-	On-treatment qHBsAg can be used as an early predictor of SVR	On-treatment decline in HBsAg appears to be genotype dependent. Genotype B patients showed the most rapid and pronounced decline
Hou et al[66]	Peg-IFN vs LAM	-	-	Peg-IFN was superior to ADV in HBeAg seroconversion and qHBsAg decline in LAM-resistant patients

HBV: Hepatitis B virus; HBsAg: Hepatitis B surface antigen; qHBsAg: Quantification of HBsAg titers; HBeAg: Hepatitis B e antigen; CHB: chronic hepatitis B; ADV: Adefovir; LAM: Lamivudine; Peg-IFN: Pegylated interferon; cccDNA: Covalently closed circular DNA; FAM: Famciclovir; SVR: Sustained virologic response; ROC: Receiver operating characteristic.

Table 2 Mutations in viral polymerase gene induced by oral antiviral agents and corresponding changes in hepatitis B surface antigen

Polymerase domain	Mutation in polymerase	Oral antiviral agents	Corresponding change in HBsAg
B	rtI169T	ETV	sF161H/L
	rtL180M	LAM, LdT	No change
	rtA181T	ADV, TFV, LAM, LdT	sW1721
	rtA181T	ADV, TFV, LAM, LdT	sW172L
	rtA181V	ADV, TFV, LdT	sL173F
	rtT184A	ETV	No change
	rtT184C	ETV	sL175F + sL176V
	rtT184I	ETV	No change
	rtT184G	ETV	sL176V
	rtT184S	ETV	sL175F
	rtT184M	ETV	sL1761
	rtT184L	ETV	sL175F
C	rtS202C	ETV	No change/sS193F
	rtS202I	ETV	sV194F/S
	rtS202G	ETV	No change/sS193L
	rtM204V	LAM	sI195M
	rtM204I	LAM, LdT	sW1961/S/L
D	rtN236T	ADV, TFV	After end of HBsAg
E	rtM250I	ETV	After end of HBsAg
	rtM250V	ETV	After end of HBsAg

¹Stop codon. Modified from reference[50]. HBsAg: Hepatitis B surface antigen; ETV: Entecavir; LAM: Lamivudine; LdT: Telbivudine; ADV: Adefovir; TFV: Tenofovir.