Hepatitis B virus genotypes and resistance mutations in patients under long term lamivudine therapy:

January 23, 2008

Research article

Hepatitis B virus genotypes and resistance mutations in patients under long term

lamivudine therapy: characterization of genotype G in Brazil

Marcelle Bottecchia , Francisco J.D. Souto , Kycia M.R. O , Marcia Amendola ,

E Brandao , Christian Niel and Selma A Gomes

BMC Microbiology 2008, 8:11doi:10.1186/1471-2180-8-11

Published: 22 January 2008

Abstract (provisional)

Background

Lamivudine is an oral nucleoside analogue widely used for the treatment of

chronic hepatitis B. The main limitation of lamivudine use is the selection of

resistant mutations that increases with time of utilization. Hepatitis B virus

(HBV) isolates have been classified into eight genotypes (A to H) with distinct

geographical distributions. HBV genotypes may also influence pathogenic

properties and therapeutic features. Here, we analyzed the HBV genotype

distribution and the nature and frequency of lamivudine resistant mutations

among 36 patients submitted to lamivudine treatment for 12 to 84 months.

Results

Half of the patients were homosexual men. Only 4/36 (11%) patients were HBV DNA

negative. As expected for a Brazilian group, genotypes A (24/32 positive

individuals, 75%), D (3/32, 9.3%) and F (1/32, 3%) were present. One sample was

from genotype C, which is a genotype rarely found in Brazil. Three samples were

from genotype G, which had not been previously detected in Brazil. Lamivudine

resistance mutations were identified in 20/32 (62%) HBV DNA positive samples.

Mean HBV loads of patients with and without lamivudine resistance mutations were

not very different (2.7 x 107 and 6.9 x 107 copies/mL, respectively). Fifteen

patients showed the L180M/M204V lamivudine resistant double mutation. The triple

mutant rt173V/180M/204V, that acts as a vaccine escape mutant, was found in two

individuals. The three isolates of genotype G were entirely sequenced. All three

showed the double mutation L180M/M204V and displayed a large genetic divergence

when compared with other full-length genotype G isolates.

Conclusions

A high (55%) proportion of patients submitted to long term lamivudine therapy

displayed resistant mutations, with elevated viral load. The potential of

transmission of such HBV mutants should be monitored. The identification of

genotypes C and G, rarely detected in South America, seems to indicate a

genotype distribution different to that observed in non treated patients.

Disparities in routes of transmission (genotype G seems to be linked to

homosexual behavior) and in pathogenic properties (genotype C is very

aggressive) among HBV genotypes may explain the presence of rare genotypes in

the present work.

The complete article is available as a provisional PDF. The fully formatted PDF

and HTML versions are in production.

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January 23, 2008