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

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Lamivudine resistance and other mutations in the polymerase and surface antigen

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

Authors: Bottecchia, Marcelle1; Ikuta, Nilo2; Niel, Christian1; Araujo, Natalia

M1; Ó, Kycia MR; Gomes, Selma A

Source: Journal of Gastroenterology and Hepatology, Volume 23, Number 1, January

2008 , pp. 67-72(6)

Publisher: Blackwell Publishing

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.

Keywords: hepatitis B virus; lamivudine; mutations; polymerase; surface antigen

Document Type: Research article

DOI: 10.1111/j.1440-1746.2007.05238.x

Affiliations: 1: Molecular Virology Laboratory, Oswaldo Cruz Institute, Rio de

Janeiro, 2: Molecular Diagnostic Laboratory, Lutheran University of Brazil,

Canoas, and

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essionid=14wuwe35dx6et.victoria

_________________________________________________________________

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[Guest guest]

Lamivudine resistance and other mutations in the polymerase and surface antigen

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

Authors: Bottecchia, Marcelle1; Ikuta, Nilo2; Niel, Christian1; Araujo, Natalia

M1; Ó, Kycia MR; Gomes, Selma A

Source: Journal of Gastroenterology and Hepatology, Volume 23, Number 1, January

2008 , pp. 67-72(6)

Publisher: Blackwell Publishing

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.

Keywords: hepatitis B virus; lamivudine; mutations; polymerase; surface antigen

Document Type: Research article

DOI: 10.1111/j.1440-1746.2007.05238.x

Affiliations: 1: Molecular Virology Laboratory, Oswaldo Cruz Institute, Rio de

Janeiro, 2: Molecular Diagnostic Laboratory, Lutheran University of Brazil,

Canoas, and

http://www.ingentaconnect.com/content/bsc/jgh/2008/00000023/00000001/art00013;js\

essionid=14wuwe35dx6et.victoria

_________________________________________________________________

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

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