title: Fatal liver failure with the emergence of hepatitis B surface antigen variants with multiple stop mutations after discontinuation of lamivudine therapy.
abstract: Treatment of chronic hepatitis B virus (HBV) infection with lamivudine is effective and well-tolerated. However, discontinuation of the treatment is associated frequently with acute exacerbation of liver diseases. A patient suffering from acute liver failure after discontinuation of lamivudine treatment is described. The patient was treated with lamivudine for 4 months and ceased the treatment without consulting. After receiving lamivudine, the patient developed anti-HBs and became negative for hepatitis B surface antigens (HBsAg). However, HBV DNA reappeared to a level of 6.47 x 10(5) copies/ml. The patient died due to acute liver failure. Sequencing of HBV isolates revealed that mutations including G145R and stop codons occurred within the HBsAg coding region. In conclusion, HBV replication resumed after the uncontrolled cessation of lamivudine treatment in this patient and may have triggered the process leading to liver failure. Anti-HBs antibody appeared and may be the selective force for the emergence of HBV mutants.
authors.affiliation: Institute of Virology, University Hospital of Essen, Essen, Germany. jimzhang@fudan.edu.cn
authors.forename: Ji-Ming
authors.initials: JM
authors.lastname: Zhang
authors.forename: Xin-Yu
authors.initials: XY
authors.lastname: Wang
authors.forename: Yu-Xian
authors.initials: YX
authors.lastname: Huang
authors.forename: You-Kuan
authors.initials: YK
authors.lastname: Yin
authors.forename: Shihe
authors.initials: S
authors.lastname: Guan
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.forename: Michael
authors.initials: M
authors.lastname: Roggendorf
authors.forename: Mengji
authors.initials: M
authors.lastname: Lu
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000627:therapeutic use; D004279:DNA, Viral / Q000097:blood; D017809:Fatal Outcome; D006510:Hepatitis B Antibodies / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000097:blood / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics* / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D017093:Liver Failure / Q000821:virology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D019259:Lamivudine