title: Characterization of naturally occurring and Lamivudine-induced surface gene mutants of hepatitis B virus in patients with chronic hepatitis B in India.
abstract: BACKGROUND
  Besides vaccine escape or immune escape hepatitis B virus (HBV) mutants, naturally occurring and drug-induced mutations have been reported in the surface gene (S-gene) of HBV.
  
  
  OBJECTIVE
  To investigate the frequency and profile of naturally occurring S-gene mutants and the influence of long-term lamivudine therapy in patients with chronic hepatitis B (CHB).
  
  
  METHODS
  57 patients with histologically proven CHB, on lamivudine 100 mg/day for more than 24 months, were included. Viral DNA was extracted at baseline and from on-therapy serum samples. The region encoding the complete major hydrophilic region (MHR) and flanking regions (nucleotides 425-840) of major S-gene that overlapped with the viral polymerase was PCR amplified and sequenced. End-of-therapy response (ETR) was assessed.
  
  
  RESULTS
  Two (3.5%) patients had naturally occurring HBV mutants, sP127S and sS143L seen in the 'a' determinant of the S-gene. Following lamivudine therapy, 14 of 57 (24.5%) patients developed 16 types of S-gene mutations (sP120S, sA128V, sS143L, sW182St., sT189I, sV190A, sS193L, sI195M, sW196L, sW196St., sS207R, sI208T, sS210E, sF219S, sF220L and sC221G). Thirteen (81.2%) of these mutations emerged downstream to the MHR. Nine of 16 types of S-gene mutations observed with lamivudine therapy were also associated with the corresponding changes in the polymerase gene. Baseline viral DNA was significantly higher (2,093 vs. 336 pg/ml; p < 0.05) among patients developing S-gene mutants and the ETR in them was significantly lower [3 of 16 (18.8%) vs. 17 of 41 (41.5%); p < 0.05].
  
  
  CONCLUSIONS
  Naturally occurring S-gene mutations are uncommon and are restricted to the 'a' determinant region. Mutations develop in about a quarter of the patients on lamivudine therapy, mostly downstream to the MHR. They may contribute to non-response to the antiviral therapy.
authors.affiliation: Department of Gastroenterology, G.B. Pant Hospital, New Delhi, India.
authors.forename: Syed Naqui
authors.initials: SN
authors.lastname: Kazim
authors.forename: Shiv Kumar
authors.initials: SK
authors.lastname: Sarin
authors.forename: Barjesh Chander
authors.initials: BC
authors.lastname: Sharma
authors.forename: Luqman Ahmad
authors.initials: LA
authors.lastname: Khan
authors.forename: Seyed Ehtesham
authors.initials: SE
authors.lastname: Hasnain
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D005814:Genes, Viral / Q000187:drug effects; D006514:Hepatitis B Surface Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D007194:India; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D006514:Hepatitis B Surface Antigens; D019259:Lamivudine