Drug resistance is a major limitation for the long-term efficacy of
antiviral therapy with nucleos(t)ide analogues (
NAs) in
chronic hepatitis B (CHB).
Antiviral resistance mutations may pre-exist in the overall viral population of untreated patients. We aimed to assess the prevalence of such hepatitis B virus (HBV) variants in a large cohort of
NAs-naïve patients with CHB and to explore possible association with viral and host variables. Serum samples from 286
NAs-naïve consecutive patients with CHB were tested for serum HBV-
DNA, and 255 of them having HBV-DNA > 1000 IU/mL were further analysed for drug resistance mutations by INNO-LiPA HBV DRv2/v3.
NAs-naïve patients analysed were mainly men (73%), Caucasians (85%),
hepatitis B e Antigen (
HBeAg) negative (79%) and genotype D (69%), with a mean age of 43.2 ± 13.4 years. HBV mutations associated with antiviral drug resistance were detected in 13 (5%) patients: three patients infected with HBV genotype C had the rtM204V + rtL180M mutations associated with
lamivudine (LMV) resistance. Four patients had the rtI233V mutation that may reduce sensitivity to
adefovir, and three patients had the rtM250L/V mutation typical of
entecavir resistance. LMV compensatory mutations rtL80V and rtV173L were seen in two and one patients, respectively. No relationship was seen between presence of resistant or compensatory mutations and HBV-
DNA levels,
HBeAg/anti-HBe status or previous IFN
therapy. These results confirm that HBV mutations, which confer resistance against currently available anti-HBV
NAs, may already exist in patients who have never received the
drug.