Clin Mol Hepatol.  2014 Sep;20(3):251-260. 10.3350/cmh.2014.20.3.251.

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

• Kim KH
• Chang HY
• Park JY
• Park ES
• Park YK
• Han KH
• Ahn SH

• KMID: 2069761
• DOI: http://doi.org/10.3350/cmh.2014.20.3.251

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.

Keyword

Hepatitis B virus; HBsAg loss; ccc DNA; Mutation

MeSH Terms

Adult
Aged
Amino Acid Sequence
Antiviral Agents/therapeutic use
DNA, Circular/*analysis
Female
Genotype
Hep G2 Cells
Hepatitis B/drug therapy/*pathology/virology
Hepatitis B Surface Antigens/blood/*genetics/metabolism
Hepatitis B virus/genetics/*metabolism
Humans
Liver/virology
Male
Middle Aged
Molecular Sequence Data
Mutation
Remission, Spontaneous
Republic of Korea
Serotyping
Antiviral Agents
DNA, Circular
Hepatitis B Surface Antigens