Natural history of chronic hepatitis B virus infection from infancy to adult life -the mechanism of inflammation triggering and long-term impacts

Table 1 Host and viral factors associated with the natural course of chronic hepatitis B virus (HBV) infection

Clinical events	Associate factors	References
Hepatitis B e antigen (HBeAg) seroconversion	Host factors
	Puberty onset	[19, 20]
	Steroid 5-alpha reductase type II	[19]
	Dehydroepiandrosterone sulphate	[26]
	Human leukocyte antigen (HLA)-B61 and HLA-DQB1*0503	[39]
	Interleukin-10 and 12	[42]
	Toll-like receptor-5 and -9	[43]
	Furin	[68, 69]
	Program death 1 and program death ligand-1 pathway	[46, 48, 70]
	Virus factors
	HBV Genotype	[40–52]
	HBV mutant strains (core-promotor, precore, core gene)	[54, 57, 58, 67]
	HBV viral load	[26]
HBV viral titer decrement	Host factors
	Puberty onset	[19]
	Dehydroepiandrosterone sulphate	[26]
	Virus factors
	HBV mutant strains (core-promotor, precore, core gene)	[54, 57, 58, 67]
Hepatitis B surface antigen (HBsAg) seroclearance/seroconversion	Host factors
	Dehydroepiandrosterone sulphate	[26]
	Gut microbiota	[47]
	Menarche onset (in females)	[20]
	HLA (DRB11301-02, DR2, DR7, DR0406, B*4001, DPA1 and DPB1)	[33–38]
	Interleukin-10 and 12	[45]
	Tumor necrosis factor alpha	[41]
	Toll-like receptor-4	[43, 47]
	Program death 1 and program death ligand-1 pathway	[46, 48, 70]
	Breakthrough of immune tolerance	[45]
	HBeAg seroconversion at childhood	[45]
	Virus factors
	HBV viral load	[45]
	HBsAg titer	[45]
HBeAg-negative hepatitis	HBeAg seroconversion age	[10–12, 60, 75]
	HBV mutant	[57, 75]