title: Spontaneous HBsAg loss in Korean patients: relevance of viral genotypes, S gene mutations, and covalently closed circular DNA copy numbers.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Pharmacology and Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul, Korea. ; KU Open Innovation Center, Konkuk University, Seoul, Korea. ; Research Institute of Medical Sciences, Konkuk University, Seoul, Korea.
authors.forename: Kyun-Hwan
authors.initials: KH
authors.lastname: Kim
authors.affiliation: Deparment of Internal medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hye-Young
authors.initials: HY
authors.lastname: Chang
authors.affiliation: Deparment of Internal medicine, Yonsei University College of Medicine, Seoul, Korea. ; Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea. ; Liver Cirrhosis Clinical Research Center, Seoul, Korea.
authors.forename: Jun Yong
authors.initials: JY
authors.lastname: Park
authors.affiliation: Department of Pharmacology and Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul, Korea. ; KU Open Innovation Center, Konkuk University, Seoul, Korea.
authors.forename: Eun-Sook
authors.initials: ES
authors.lastname: Park
authors.affiliation: Department of Pharmacology and Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul, Korea.
authors.forename: Yong Kwang
authors.initials: YK
authors.lastname: Park
authors.affiliation: Deparment of Internal medicine, Yonsei University College of Medicine, Seoul, Korea. ; Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea. ; Liver Cirrhosis Clinical Research Center, Seoul, Korea.
authors.forename: Kwang-Hyub
authors.initials: KH
authors.lastname: Han
authors.affiliation: Deparment of Internal medicine, Yonsei University College of Medicine, Seoul, Korea. ; Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea. ; Liver Cirrhosis Clinical Research Center, Seoul, Korea.
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Ahn
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000627:therapeutic use; D004270:DNA, Circular / Q000032:analysis*; D005260:Female; D005838:Genotype; D056945:Hep G2 Cells; D006509:Hepatitis B / Q000188:drug therapy / Q000473:pathology* / Q000821:virology; D006514:Hepatitis B Surface Antigens / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D006515:Hepatitis B virus / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000821:virology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D012075:Remission, Spontaneous; D056910:Republic of Korea; D012703:Serotyping
chemical_list: D000998:Antiviral Agents; D004270:DNA, Circular; D006514:Hepatitis B Surface Antigens
keywords: HBsAg loss; Hepatitis B virus; Mutation; ccc DNA