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 |
1
Resistance to ADV or TDF is associated with the substitution A181T/V and/or N235T in HBV polymerase gene;
2
Resistance 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.