Table1. Genotypic resistance patterns of multidrug-resistant HBV strain in sequential NUCs mono and combine therapy.
| Sequential NUCs therapy (Dec. 2004 – Feb. 2009) | Resistance detection method (application time in the treatment) | Primary resistance | Compensatory resistance | Resistance to |
| LAM | Direct sequencing (13th month) | M552Va (rtM204V) | L528Ma (rtL180M), V555V (rtV207V) | LAM and ETV (intermediate)b |
| LAM + ADV | NTc | NT | NT | - |
| ADV | LIPA (11th month) | rtN236T (Wild type:N236) | (Wild type:L80) | ADV and TDF (intermediate)d |
| ADV | Clonal analysis (on 6 clones) (11th month) | rtM204I (in clone 2, 5) rtA181V (in clone 4) | rtL80V (in clone 2, 3, 5) | LAM, LdT, ADV |
| ADV + ETV | Direct sequencing (5th month) | - | rtQ215H | - |
| ETV | Direct sequencing (18th month) | rtM204V | rtV173L, rtL180M | LAM and ETV (intermediate) |
| ETV | LIPA (18th month) | rtM204V, rtN236T, tA181V/T (Wild type:M204, N236)f | rtV173L, rtL180Me, rtL80I/V (Wild type:L80, V173, L180/A181)f | LAM, ADV and TDF (intermediate) |
| ETV + TDF | Direct sequencing (4th month) | rtM204V | rtV173L, rtL180M | LAM and ETV (intermediate) |
| ETV + TDF | LIPA (4th month) | rtM204V (Wild type:N236) | rtV173Le, rtL180M (Wild type:L80, L180/A181) | LAM and ETV (intermediate) |
| ETV + TDF | Clonal analysis (5 clones) (4th month) | rtM204V (in clone 1-5) | rtV173L, rtL180M (in all clones) | LAM and ETV (intermediate |
a LAM – associated amino acids at position M552, L528 and V555 is previous nomenclature[20]
b ETV intermediate: by L180M+M204V mutations; according to EASL Clinical Practice Guidelines 2009[1]
c NT: Not tested
d TDF intermediate: by N236T mutation; according to EASL Clinical Practice Guidelines 2009[1]
e Detected after nested HBV PCR.
f When band densities in LIPA assays are compared, wild-type probe band is denser than variant-type probe bands in this LIPA assay and of equal density in others LIPA assays.