Clinical relevance of hepatitis B virus variants

Table 1 Summary of clinically revelant hepatitis B virus variants

Location	Amino acid or nucleotide substitution(associated overlapping gene mutation)	Clinical impact
P (RT-A)	rtI169T (sF161L)	ETV resistance
P (RT-B)	rtL180M (sE164D)	ETV resistance
P (RT-B)	rtA181T/V	LMV, LdT, ADF/TDF resistance
P (RT-B)	rtT184S/A/I/L/G/CM	ETV resistance
P (RT-C)	rtS202C/G/I	ETV resistance
P (RT-C)	rtM204V/I	LAM resistance
P (RT-C)	rtM204I (sW196S)	LdT resistance
P (RT-C)	rtM204V (sI195M)	ETV resistance
P (RT-D)	rtN236T	ADF/TDF resistance
P (RT-E)	rtM250I/V	ETV resistance
P (RT-A)	rtL80V/I	Poor antiviral response to ADF with prior LMV resistant variants
P (RT-B)	rtF166L (sF158Y)	LMV-associated, compensatory
P (RT-B)	rtV173L (sE164D)	Compensatory mutation associated with LMV resistance (enhanced replication)
P (RT-B)	rtA194T	TDF resistance
S ("a" determinant)	sG145R (rtW153Q)	Antibody-associated escape mutation; reduced HBsAg level; restore LMV resistant HBV replication
S ("a" determinant)	sD144E/G145R (rtG153E)	Antibody-associated escape mutation
S ("a" determinant)	sP120T (rtT128N)	Reduced HBsAg level
EnhII	C1653T	HCC development (genotype C)
BCP	T1753V	HCC development (genotype B)
BCP	A1762T/G1764A	HBeAg production reduced by 50%; HBeAg seroconversion; escape anti-HBe immunity
Pre-C	G1896A	HBeAg seroconverstion; escape anti-HBe immunity; more severe course of disease; HCC development
S	W172* (rtA181T)	Cirrhosis and HCC development
Pre-S1/Pre-S2	Pre-S1/pre-S2 deletion (pre-S2 start codon and/or deletions in the 5'-terminal half of the pre-S2 region and pre-S1 3'-terminal half of the pre-S1 region)	More common in genotype C; progressive liver diseases; HCC development
Pre-S	Pre-S1 promoter mutation	HCC development
	Pre-S2 promoter mutation
X	K130M + V131I (double)	HCC development
X	V5M/L + K130M + V131I (triple)	HCC development

HCC: Hepatocellular carcinoma; BCP: Basal core promoter; HBeAg: HBV e antigen; HBV: Hepatitis B virus; ADF: Adefovir; TDF: Tenofovir; LMV: Lamivudine; HBsAg: Hepatitis B surface (S) antigen; LdT: Telbivudine; ETV: Entecavir; RT: Reverse transcriptase.