Spontaneous HBsAg loss in Korean patients: relevance of viral genotypes, S gene mutations, and covalently closed circular DNA copy numbers

Kyun Hwan Kim, Hye Young Chang, Jun Y.ong Park, Eun Sook Park, Yong K.wang Park, Kwang Hyub Han, Sang H.oon Ahn

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

BACKGROUND/AIMS: Occult HBV infection can persist following HBsAg loss and be transmitted, but the virological features are not well defined.

METHODS: Here we investigated 25 Korean patients who lost HBsAg during follow up, either spontaneously or subsequent to therapy.

RESULTS: Whereas subtype adr (genotype C) was found in 96% of HBsAg positive patients, 75 % of patients who lost HBsAg spontaneously were seemed to be infected with the ayw subtype with sequence similar to genotype D. Mutations in the major hydrophilic region (MHR) of HBsAg were found in 7 patients who lost HBsAg spontaneously. The mutations include T123S, M125I/N, C139R, D144E, V177A, L192F, and W196L, some of which have not been reported before. Functional analysis via transfection experiments indicate that the C139R and D144E mutations drastically reduced HBsAg antigenicity, while the Y225del mutation found in one interferon-treated patient impaired HBsAg secretion.

CONCLUSIONS: Lack of detectable HBsAg in patient serum could be explained by low level of ccc DNA in liver tissue, low antigenicity of the surface protein, or its secretion defect.

Original languageEnglish
Pages (from-to)251-260
Number of pages10
JournalClinical and Molecular Hepatology
Volume20
Issue number3
DOIs
Publication statusPublished - 2014 Sep 1

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Circular DNA
Hepatitis B Surface Antigens
Genotype
Mutation
Genes
Interferons
Transfection
Membrane Proteins

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Molecular Biology

Cite this

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title = "Spontaneous HBsAg loss in Korean patients: relevance of viral genotypes, S gene mutations, and covalently closed circular DNA copy numbers",
abstract = "BACKGROUND/AIMS: Occult HBV infection can persist following HBsAg loss and be transmitted, but the virological features are not well defined.METHODS: Here we investigated 25 Korean patients who lost HBsAg during follow up, either spontaneously or subsequent to therapy.RESULTS: Whereas subtype adr (genotype C) was found in 96{\%} of HBsAg positive patients, 75 {\%} of patients who lost HBsAg spontaneously were seemed to be infected with the ayw subtype with sequence similar to genotype D. Mutations in the major hydrophilic region (MHR) of HBsAg were found in 7 patients who lost HBsAg spontaneously. The mutations include T123S, M125I/N, C139R, D144E, V177A, L192F, and W196L, some of which have not been reported before. Functional analysis via transfection experiments indicate that the C139R and D144E mutations drastically reduced HBsAg antigenicity, while the Y225del mutation found in one interferon-treated patient impaired HBsAg secretion.CONCLUSIONS: Lack of detectable HBsAg in patient serum could be explained by low level of ccc DNA in liver tissue, low antigenicity of the surface protein, or its secretion defect.",
author = "Kim, {Kyun Hwan} and Chang, {Hye Young} and Park, {Jun Y.ong} and Park, {Eun Sook} and Park, {Yong K.wang} and Han, {Kwang Hyub} and Ahn, {Sang H.oon}",
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Spontaneous HBsAg loss in Korean patients : relevance of viral genotypes, S gene mutations, and covalently closed circular DNA copy numbers. / Kim, Kyun Hwan; Chang, Hye Young; Park, Jun Y.ong; Park, Eun Sook; Park, Yong K.wang; Han, Kwang Hyub; Ahn, Sang H.oon.

In: Clinical and Molecular Hepatology, Vol. 20, No. 3, 01.09.2014, p. 251-260.

Research output: Contribution to journalArticle

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AU - Kim, Kyun Hwan

AU - Chang, Hye Young

AU - Park, Jun Y.ong

AU - Park, Eun Sook

AU - Park, Yong K.wang

AU - Han, Kwang Hyub

AU - Ahn, Sang H.oon

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N2 - BACKGROUND/AIMS: Occult HBV infection can persist following HBsAg loss and be transmitted, but the virological features are not well defined.METHODS: Here we investigated 25 Korean patients who lost HBsAg during follow up, either spontaneously or subsequent to therapy.RESULTS: Whereas subtype adr (genotype C) was found in 96% of HBsAg positive patients, 75 % of patients who lost HBsAg spontaneously were seemed to be infected with the ayw subtype with sequence similar to genotype D. Mutations in the major hydrophilic region (MHR) of HBsAg were found in 7 patients who lost HBsAg spontaneously. The mutations include T123S, M125I/N, C139R, D144E, V177A, L192F, and W196L, some of which have not been reported before. Functional analysis via transfection experiments indicate that the C139R and D144E mutations drastically reduced HBsAg antigenicity, while the Y225del mutation found in one interferon-treated patient impaired HBsAg secretion.CONCLUSIONS: Lack of detectable HBsAg in patient serum could be explained by low level of ccc DNA in liver tissue, low antigenicity of the surface protein, or its secretion defect.

AB - BACKGROUND/AIMS: Occult HBV infection can persist following HBsAg loss and be transmitted, but the virological features are not well defined.METHODS: Here we investigated 25 Korean patients who lost HBsAg during follow up, either spontaneously or subsequent to therapy.RESULTS: Whereas subtype adr (genotype C) was found in 96% of HBsAg positive patients, 75 % of patients who lost HBsAg spontaneously were seemed to be infected with the ayw subtype with sequence similar to genotype D. Mutations in the major hydrophilic region (MHR) of HBsAg were found in 7 patients who lost HBsAg spontaneously. The mutations include T123S, M125I/N, C139R, D144E, V177A, L192F, and W196L, some of which have not been reported before. Functional analysis via transfection experiments indicate that the C139R and D144E mutations drastically reduced HBsAg antigenicity, while the Y225del mutation found in one interferon-treated patient impaired HBsAg secretion.CONCLUSIONS: Lack of detectable HBsAg in patient serum could be explained by low level of ccc DNA in liver tissue, low antigenicity of the surface protein, or its secretion defect.

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