title: Interferon/long-term lamivudine combination therapy in anti-HBe positive chronic hepatitis B patients.
abstract: BACKGROUND
  Monotherapy with a single antiviral agent is insufficient in controlling hepatitis B virus infection in the majority of patients with anti-HBe positive chronic hepatitis B. Interferon/long-term lamivudine combination therapy was evaluated to determine if this strategy would improve treatment efficacy and reduce the emergence of lamivudine resistance.
  
  
  METHODS
  In total, 36 consecutive anti-HBe positive patients were treated with interferon (3 MU subcutaneously three times weekly) and lamivudine (100 mg orally once a day) for 12 months. After completion of the combined treatment, all patients continued to receive lamivudine monotherapy indefinitely.
  
  
  RESULTS
  Overall, 35 patients (97%) showed virological response at 12 months. Four patients (11%) cleared HBsAg and developed anti-HBs. During the follow-up time, after the discontinuation of interferon, of 30 +/- 12 months (range: 7-57 months), 13 patients (36%) exhibited breakthrough infection. The cumulative rates of breakthrough infection at the end of 1, 2, 3 and 4 years of treatment were 0%, 14%, 32%, and 59%, respectively.
  
  
  CONCLUSIONS
  Combination therapy appears to be effective and may also delay the selection of lamivudine-resistant variants. However, controlled trials are definitely warranted to clarify the potential benefits of combination antiviral treatment over monotherapy.
authors.affiliation: Gastroenterology and Hepatology Section of Second Propaedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece. niknik@med.auth.gr
authors.forename: Nikolaos L
authors.initials: NL
authors.lastname: Nikolaidis
authors.forename: Olga I
authors.initials: OI
authors.lastname: Giouleme
authors.forename: Konstantinos A
authors.initials: KA
authors.lastname: Tziomalos
authors.forename: Adamos S
authors.initials: AS
authors.lastname: Saveriadis
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Grammatikos
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Doukelis
authors.forename: Anastasios D
authors.initials: AD
authors.lastname: Voutsas
authors.forename: Themistoklis
authors.initials: T
authors.lastname: Vassiliadis
authors.forename: Kalliopi
authors.initials: K
authors.lastname: Patsiaoura
authors.forename: Eleni
authors.initials: E
authors.lastname: Orfanou-Koumerkeridou
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Balaska
authors.forename: Nikolaos P
authors.initials: NP
authors.lastname: Eugenidis
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D006510:Hepatitis B Antibodies / Q000097:blood*; D006513:Hepatitis B e Antigens / Q000276:immunology*; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D019259:Lamivudine / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012008:Recurrence; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D000998:Antiviral Agents; D006510:Hepatitis B Antibodies; D006513:Hepatitis B e Antigens; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D007372:Interferons