title: Combination therapy with lamivudine and famciclovir for chronic hepatitis B infection.
abstract: OBJECTIVE
  Lamivudine suppresses hepatitis B replication, but drug-resistant mutants emerge with long-term therapy. In vitro data suggest that lamivudine and famciclovir might synergistically inhibit hepadnaviral replication. We reviewed our experience with lamivudine and famciclovir in 24 patients with chronic hepatitis B infection.
  
  
  METHODS
  Patients with chronic hepatitis B infection and detectable HBV DNA received lamivudine and famciclovir combination therapy. The primary end point was HBV DNA suppression at week 48. Follow-up was reviewed for those who remained on combination therapy beyond the first 48 weeks.
  
  
  RESULTS
  Thirteen treatment-naïve HBeAg-positive subjects received 48 weeks of therapy; all had undetectable HBV DNA levels (less than 2.5 pg/mL) at week 48. Three patients underwent HBeAg seroconversion at week 48 and discontinued therapy. Ten patients remained on combination therapy; 3 developed YMDD (tyrosine-methionine-aspartate-aspartate) mutations at year 2, although HBV DNA levels remained below 2.5 pg/mL at a mean of 39 months. A second heterogeneous group of 5 subjects including interferon therapy failures and those with HBeAg-negative infection also received 48 weeks of combination therapy, with 1 subject developing redetection of HBV DNA by week 48. YMDD mutations were noted in the other 4 subjects at year 2, although just 1 subject had HBV DNA greater than 2.5 pg/mL at 39 months of therapy.
  
  
  CONCLUSIONS
  In this small pilot study, 48 weeks of therapy with lamivudine and famciclovir was effective in suppressing HBV replication. A randomized controlled trial is required to define the role of combination therapy with lamivudine and famciclovir in delaying the clinical emergence of resistant strains.
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, 46202, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Shen
authors.forename: Mazen
authors.initials: M
authors.lastname: Alsatie
authors.forename: George
authors.initials: G
authors.lastname: Eckert
authors.forename: Naga
authors.initials: N
authors.lastname: Chalasani
authors.forename: Lawrence
authors.initials: L
authors.lastname: Lumeng
authors.forename: Paul Y
authors.initials: PY
authors.lastname: Kwo
mesh_terms: D015075:2-Aminopurine / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage; D004279:DNA, Viral / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D000077595:Famciclovir; D005260:Female; D005500:Follow-Up Studies; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D018570:Risk Assessment; D012720:Severity of Illness Index; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D019259:Lamivudine; D015075:2-Aminopurine; D000077595:Famciclovir