title: The effect of pegylated interferon-alpha on the treatment of lamivudine resistant chronic HBeAg positive hepatitis B virus infection.
abstract: OBJECTIVE
  To determine the response to pegylated interferon-alpha treatment of HBeAg-positive hepatitis B patients with proven lamivudine resistance.
  
  
  METHODS
  Sixteen HBeAg-positive HBV patients with YMDD mutations were treated with pegylated interferon. Median treatment duration was 52 weeks (range 20-53), with a 26-week follow-up.
  
  
  RESULTS
  Two of 16 (12.5%) patients seroconverted to HBeAg negative and achieved sustained virological (HBV-DNA levels below 10log 5 copies/ml) together with biochemical (normalization of serum ALT levels) responses. Compared with the strong signal in all other patients, only these two patients had a faint signal in the lamivudine resistance assay. For all patients, the median viral load decreased from 10log 9.4 to 7.9 copies/ml (P = 0.001) during treatment but rebounded to a median of 10log 8.7 copies/ml after treatment cessation. Similarly, elevated median ALT levels at baseline decreased with treatment but rebounded after the end of treatment.
  
  
  CONCLUSIONS
  In the largest cohort study to date, pegylated interferon-alpha therapy showed marginal efficacy in the presence of lamivudine resistance but such therapy may be beneficial in patients with only small amounts of mutant virus. In our opinion, an analysis of the patient subgroup harbouring an YMDD-mutation should be included in all future studies of pegylated interferon-alpha in chronic hepatitis B.
authors.affiliation: Department of Gastroenterology & Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Wilhelmus F
authors.initials: WF
authors.lastname: Leemans
authors.forename: Hajo J
authors.initials: HJ
authors.lastname: Flink
authors.forename: Harry L A
authors.initials: HL
authors.lastname: Janssen
authors.forename: Hubert G M
authors.initials: HG
authors.lastname: Niesters
authors.forename: Solko W
authors.initials: SW
authors.lastname: Schalm
authors.forename: Robert A
authors.initials: RA
authors.lastname: de Man
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000032:analysis; D004337:Drug Carriers; D024882:Drug Resistance, Viral / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D006513:Hepatitis B e Antigens / Q000276:immunology*; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000201:enzymology / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D004337:Drug Carriers; D006513:Hepatitis B e Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D011092:Polyethylene Glycols; D000410:Alanine Transaminase; C417083:peginterferon alfa-2b