title: Overlapping gene mutations of hepatitis B virus in a chronic hepatitis B patient with hepatitis B surface antigen loss during lamivudine therapy.
abstract: Disappearance of hepatitis B surface antigens (HBsAg) in chronic hepatitis B usually indicates clearance of hepatitis B virus (HBV) infection. However, false HBsAg negativity with mutations in pre-S2 and 'a' determinant has been reported. It is also known that YMDD mutations decrease the production of HBV and escape detection of serum HBsAg. Here, we report overlapping gene mutations in a patient with HBsAg loss during the lamivudine therapy. After 36 months of lamivudine therapy in a 44-yrold Korean chronic hepatitis B patient, serum HBsAg turned negative while HBV DNA remained positive by a DNA probe method. Nucleotide sequence of serum HBV DNA was compared with the HBV genotype C subtype adr registered in NCBI AF 286594. Deletion of nucleotides 23 to 55 (amino acids 12 to 22) was identified in the pre-S2 region. Sequencing of the 'a' determinant revealed amino acid substitutions as I126S, T131N, M133T, and S136Y. Methionine of rtM204 in the P gene was substituted for isoleucine indicating YIDD mutation (rtM204I). We identified a HBV mutant composed of pre-S2 deletions and 'a' determinant substitutions with YMDD mutation. Our result suggests that false HBsAg negativity can be induced by combination of overlapping gene mutations during the lamivudine therapy.
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Lee
authors.forename: Moon Seok
authors.initials: MS
authors.lastname: Choi
authors.forename: Dongho
authors.initials: D
authors.lastname: Lee
authors.forename: Joon Hyoek
authors.initials: JH
authors.lastname: Lee
authors.forename: Kwang Cheol
authors.initials: KC
authors.lastname: Koh
authors.forename: Seung Woon
authors.initials: SW
authors.lastname: Paik
authors.forename: Byung Chul
authors.initials: BC
authors.lastname: Yoo
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000627:therapeutic use; D001483:Base Sequence; D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000097:blood / Q000737:chemistry / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D017353:Gene Deletion; D005807:Genes, Overlapping / Q000235:genetics*; D006514:Hepatitis B Surface Antigens / Q000097:blood / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D011498:Protein Precursors / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D014764:Viral Proteins / Q000235:genetics
chemical_list: D019380:Anti-HIV Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D011498:Protein Precursors; D014764:Viral Proteins; C050807:presurface protein 2, hepatitis B surface antigen; D019259:Lamivudine; D004259:DNA-Directed DNA Polymerase