Lamivudine resistance and other mutations in the polymerase and surface antigen genes of hepatitis B

[Guest guest]

Journal of Gastroenterology and Hepatology 23 (1), 67–72.

doi:10.1111/j.1440-1746.2007.05238.x

Abstract

HEPATOLOGY

Lamivudine resistance and other mutations in the polymerase and surface antigen

genes of hepatitis B virus associated with a fatal hepatic failure case

Marcelle Bottecchia,**Molecular Virology Laboratory, Oswaldo Cruz Institute, Rio

de Janeiro, Nilo Ikuta,††Molecular Diagnostic Laboratory, Lutheran

University of Brazil, Canoas, and Christian Niel,**Molecular Virology

Laboratory, Oswaldo Cruz Institute, Rio de Janeiro, Natalia M Araujo,**Molecular

Virology Laboratory, Oswaldo Cruz Institute, Rio de Janeiro, Kycia MR

Ó,*‡*Molecular Virology Laboratory, Oswaldo Cruz Institute, Rio de Janeiro,

‡Municipal Health Foundation of Petrópolis, Petrópolis, Brazil and Selma A

Gomes**Molecular Virology Laboratory, Oswaldo Cruz Institute, Rio de Janeiro, Dr

Selma A Gomes, Molecular Virology Laboratory, Oswaldo Cruz Institute, FIOCRUZ,

Avenue Brazil 4365, 21045-900 Rio de Janeiro, RJ, Brazil. Email:

selma@... *Molecular Virology Laboratory, Oswaldo Cruz Institute, Rio

de Janeiro, †Molecular Diagnostic Laboratory, Lutheran University of Brazil,

Canoas, and ‡Municipal Health Foundation of Petrópolis, Petrópolis, Brazil

Dr Selma A Gomes, Molecular Virology Laboratory, Oswaldo Cruz Institute,

FIOCRUZ, Avenue Brazil 4365, 21045-900 Rio de Janeiro, RJ, Brazil. Email:

selma@...

The sequences reported in this paper have been deposited into GenBank under the

following accession numbers: EF034149 to EF034151.

Abstract

Background and Aim: Resistance to lamivudine therapy of chronic hepatitis B

virus (HBV) infection occurs by mutation in the YMDD motif of the reverse

transcriptase (rt) domain (rtM204V/I) of the virus polymerase, and is usually

accompanied by rtL180M mutation. Here we investigated virological factors

associated with hepatic failure in a 58-year-old male, chronically HBV-infected

patient who died after 33 months of lamivudine therapy.

Methods: Nucleotide sequencing was performed from one sample collected before

and two samples collected during lamivudine therapy.

Results: A peak of alanine aminotransferase and aspartate aminotransferase

levels occurred after 19 months of lamivudine treatment, associated with the

rtM204I mutation. After 32 months, the rtM204V mutation was predominant,

accompanied by the lamivudine-resistant rtL180M mutation. Furthermore, two rare

polymerase (rtS117Y and rtV142A) and three HBsAg (L109I, F134L, and I208T)

substitutions were observed. At that time, the patient was hospitalized with

hepatic decompensation, followed by hepatic failure, and died one month later.

HBV-DNA was detected at moderate levels (8.3 × 104−2.6 × 106 copies/mL)

throughout.

Conclusion: The results suggest that substitutions in polymerase (rtS117Y,

rtV142A) and surface antigens (L109I, F134L, and I208T), associated with

lamivudine-resistant mutations at positions 180 and 204, were involved in this

case of fatal hepatitis B.

http://www.blackwell-synergy.com/doi/abs/10.1111/j.1440-1746.2007.05238.x

_________________________________________________________________

Don't get caught with egg on your face. Play Chicktionary!

http://club.live.com/chicktionary.aspx?icid=chick_wlhmtextlink1_dec

[Guest guest]

Journal of Gastroenterology and Hepatology 23 (1), 67–72.

doi:10.1111/j.1440-1746.2007.05238.x

Abstract

HEPATOLOGY

Lamivudine resistance and other mutations in the polymerase and surface antigen

genes of hepatitis B virus associated with a fatal hepatic failure case

Marcelle Bottecchia,**Molecular Virology Laboratory, Oswaldo Cruz Institute, Rio

de Janeiro, Nilo Ikuta,††Molecular Diagnostic Laboratory, Lutheran

University of Brazil, Canoas, and Christian Niel,**Molecular Virology

Laboratory, Oswaldo Cruz Institute, Rio de Janeiro, Natalia M Araujo,**Molecular

Virology Laboratory, Oswaldo Cruz Institute, Rio de Janeiro, Kycia MR

Ó,*‡*Molecular Virology Laboratory, Oswaldo Cruz Institute, Rio de Janeiro,

‡Municipal Health Foundation of Petrópolis, Petrópolis, Brazil and Selma A

Gomes**Molecular Virology Laboratory, Oswaldo Cruz Institute, Rio de Janeiro, Dr

Selma A Gomes, Molecular Virology Laboratory, Oswaldo Cruz Institute, FIOCRUZ,

Avenue Brazil 4365, 21045-900 Rio de Janeiro, RJ, Brazil. Email:

selma@... *Molecular Virology Laboratory, Oswaldo Cruz Institute, Rio

de Janeiro, †Molecular Diagnostic Laboratory, Lutheran University of Brazil,

Canoas, and ‡Municipal Health Foundation of Petrópolis, Petrópolis, Brazil

Dr Selma A Gomes, Molecular Virology Laboratory, Oswaldo Cruz Institute,

FIOCRUZ, Avenue Brazil 4365, 21045-900 Rio de Janeiro, RJ, Brazil. Email:

selma@...

The sequences reported in this paper have been deposited into GenBank under the

following accession numbers: EF034149 to EF034151.

Abstract

Background and Aim: Resistance to lamivudine therapy of chronic hepatitis B

virus (HBV) infection occurs by mutation in the YMDD motif of the reverse

transcriptase (rt) domain (rtM204V/I) of the virus polymerase, and is usually

accompanied by rtL180M mutation. Here we investigated virological factors

associated with hepatic failure in a 58-year-old male, chronically HBV-infected

patient who died after 33 months of lamivudine therapy.

Methods: Nucleotide sequencing was performed from one sample collected before

and two samples collected during lamivudine therapy.

Results: A peak of alanine aminotransferase and aspartate aminotransferase

levels occurred after 19 months of lamivudine treatment, associated with the

rtM204I mutation. After 32 months, the rtM204V mutation was predominant,

accompanied by the lamivudine-resistant rtL180M mutation. Furthermore, two rare

polymerase (rtS117Y and rtV142A) and three HBsAg (L109I, F134L, and I208T)

substitutions were observed. At that time, the patient was hospitalized with

hepatic decompensation, followed by hepatic failure, and died one month later.

HBV-DNA was detected at moderate levels (8.3 × 104−2.6 × 106 copies/mL)

throughout.

Conclusion: The results suggest that substitutions in polymerase (rtS117Y,

rtV142A) and surface antigens (L109I, F134L, and I208T), associated with

lamivudine-resistant mutations at positions 180 and 204, were involved in this

case of fatal hepatitis B.

http://www.blackwell-synergy.com/doi/abs/10.1111/j.1440-1746.2007.05238.x

_________________________________________________________________

Don't get caught with egg on your face. Play Chicktionary!

http://club.live.com/chicktionary.aspx?icid=chick_wlhmtextlink1_dec