Nucleos(t)ide analogues to treat hepatitis B virus-related hepatocellular carcinoma after radical resection

Table 3 Mutations of the hepatitis B virus polymerase gene arising after initial therapy with one nucleos(t)ide analogue and resulting in cross-resistance to other nucleos(t)ide analogues

Initial NA therapy	Mutational sites after initial NA therapy	Cross-resistance data
		LAM	LdT	ETV	ADV	TDF
	Wild-type	S	S	S	S	S
LAM or LdT	M204I/V	R	R	I	S	S
ADV	N236T	S	S	S	R	I
LAM or LdT or ADV	A181T/V	R	R	S	R	I
ADV or TDF	A181T/V + N236T1	R	R	S	R	R
ETV	L181M + M204V/I ± I169 ± T184 ± S202 ± M250V2	R	R	R	S	S

¹Resistance to ADV or TDF is associated with the substitution A181T/V and/or N235T in HBV polymerase gene;

²Resistance to ETV is associated with substitutions at I169, T184, S202 or M250V, and with the simultaneous substitutions at L181M plus M204V/I in HBV polymerase gene. Data come from ref. [11]. ADV: Adefovir dipivoxil; ETV: Entecavir; I: Intermediate; LAM: Lamivudine; LdT: Telbivudine; NA: Nucleos(t)ide analogue; R: Resistant; S: Sensitive; TDF: Tenofovir disoproxil fumarate.