Hepatitis B functional cure: Current and future perspective

Table 3 Predictors of hepatitis B surface antigen clearance in chronic hepatitis B

Category	Subcategory	Predictor variables
Spontaneous clearance	Host factors	Male sex; older age (hazard ratio 1.16-1.21)
	Viral factors	HBeAg-negative status; genotype C infection; lower HBV DNA (≤ 20000 IU/mL); low quantitative HBsAg (≤ 1000 IU/mL)
PEG-IFN therapy	Host factors	Younger age; female sex; ALT elevation at week 12
	Treatment factors	Combination therapy (PEG-IFN + NAs) more effective than PEG-IFN alone
	Viral factors	Genotype A; low baseline HBsAg and HBV DNA; early HBsAg decline (at week 12 or 24)
NAs therapy	Treatment factors	Early HBeAg seroconversion (before age 18); initiating high-barrier NA before seroconversion
	Viral factors	Low HBsAg (< 1000 IU/mL) at 18 months post-seroconversion
NA discontinuation in HBeAg-negative CHB	Treatment factors	End-of-treatment HBsAg < 100 IU/mL; ALT/qHBsAg ratio ≥ 0.2
	Viral factor	Low HBsAg glycan isomer (≤ 3.5 Log ng/mL) associated with 5-fold higher 10-year clearance
Prediction models	Nomogram	BMI, HBeAg status, qHBsAg, HBV DNA (C-index 0.91)
	HepBLOSS-1 & HepBLOSS-2	Age, sex, HBsAg, HBV DNA; AUROC 0.81-0.89; > 50% 10-year clearance in high-risk groups
	HBRN-SQuARe	Sex, age, race, qHBsAg; AUROC 0.99 (1 year), 0.95 (3 years) in untreated HBeAg-negative CHB

HBsAg: Hepatitis B surface antigen; HBV: Hepatitis B virus; HBeAg: Hepatitis B e antigen; qHBsAg: Quantitative hepatitis B surface antigen; PEG-IFN: Pegylated interferon; NAs: Nucleos(t)ide analogues; ALT: Alanine aminotransferase; BMI: Body mass index; CHB: Chronic hepatitis B; AUROC: Area under the receiver operating characteristic curve; C-index: Concordance index; HepBLOSS: Hepatitis B Long-term Outcome Scoring System; HBRN-SQuARe: Hepatitis B Research Network-Surface Quantitative Antigen Risk estimator.