Large-scale survey of naturally occurring HBV polymerase mutations associated with anti-HBV drug resistance in untreated patients with chronic hepatitis B

[Guest guest]

J Viral Hepat. 2011 Jul;18(7):e212-6. doi: 10.1111/j.1365-2893.2011.01435.x.

Epub 2011 Jan 21.

Large-scale survey of naturally occurring HBV polymerase mutations associated

with anti-HBV drug resistance in untreated patients with chronic hepatitis B.

Mirandola S, Campagnolo D, Bortoletto G, Franceschini L, Marcolongo M, Alberti

A.

Source

Venetian Institute of Molecular Medicine, Padova, Italy Department of Histology,

Microbiology and Experimental Medicine, University of Padova, Padova, Italy.

Abstract

Summary.  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.

© 2011 Blackwell Publishing Ltd.

PMID: 21692935 [PubMed - in process]