title: Peginterferon alfa-2a alone, lamivudine alone, and the two in combination in patients with HBeAg-negative chronic hepatitis B.
abstract: BACKGROUND
  Available treatments for hepatitis B e antigen (HBeAg)-negative chronic hepatitis B are associated with poor sustained responses. As a result, nucleoside and nucleotide analogues are typically continued indefinitely, a strategy associated with the risk of resistance and unknown long-term safety implications.
  
  
  METHODS
  We compared the efficacy and safety of peginterferon alfa-2a (180 microg once weekly) plus placebo, peginterferon alfa-2a plus lamivudine (100 mg daily), and lamivudine alone in 177, 179, and 181 patients with HBeAg-negative chronic hepatitis B, respectively. Patients were treated for 48 weeks and followed for an additional 24 weeks.
  
  
  RESULTS
  After 24 weeks of follow-up, the percentage of patients with normalization of alanine aminotransferase levels or hepatitis B virus (HBV) DNA levels below 20,000 copies per milliliter was significantly higher with peginterferon alfa-2a monotherapy (59 percent and 43 percent, respectively) and peginterferon alfa-2a plus lamivudine (60 percent and 44 percent) than with lamivudine monotherapy (44 percent, P=0.004 and P=0.003, respectively; and 29 percent, P=0.007 and P=0.003, respectively). Rates of sustained suppression of HBV DNA to below 400 copies per milliliter were 19 percent with peginterferon alfa-2a monotherapy, 20 percent with combination therapy, and 7 percent with lamivudine alone (P<0.001 for both comparisons with lamivudine alone). Loss of hepatitis B surface antigen occurred in 12 patients in the peginterferon groups, as compared with 0 patients in the group given lamivudine alone. Adverse events, including pyrexia, fatigue, myalgia, and headache, were less frequent with lamivudine monotherapy than with peginterferon alfa-2a monotherapy or combination therapy.
  
  
  CONCLUSIONS
  Patients with HBeAg-negative chronic hepatitis B had significantly higher rates of response, sustained for 24 weeks after the cessation of therapy, with peginterferon alfa-2a than with lamivudine. The addition of lamivudine to peginterferon alfa-2a did not improve post-therapy response rates.
authors.affiliation: Service d'Hépatologie, INSERM Unité 481 and Centre de Recherches Claude Bernard sur les Hépatites Virales, Hôpital Beaujon, Clichy, France. patrick.marcellin@bjn.ap-hop-paris.fr
authors.forename: Patrick
authors.initials: P
authors.lastname: Marcellin
authors.forename: George K K
authors.initials: GK
authors.lastname: Lau
authors.forename: Ferruccio
authors.initials: F
authors.lastname: Bonino
authors.forename: Patrizia
authors.initials: P
authors.lastname: Farci
authors.forename: Stephanos
authors.initials: S
authors.lastname: Hadziyannis
authors.forename: Rui
authors.initials: R
authors.lastname: Jin
authors.forename: Zhi-Meng
authors.initials: ZM
authors.lastname: Lu
authors.forename: Teerha
authors.initials: T
authors.lastname: Piratvisuth
authors.forename: Georgios
authors.initials: G
authors.lastname: Germanidis
authors.forename: Cihan
authors.initials: C
authors.lastname: Yurdaydin
authors.forename: Moises
authors.initials: M
authors.lastname: Diago
authors.forename: Selim
authors.initials: S
authors.lastname: Gurel
authors.forename: Ming-Yang
authors.initials: MY
authors.lastname: Lai
authors.forename: Peter
authors.initials: P
authors.lastname: Button
authors.forename: Nigel
authors.initials: N
authors.lastname: Pluck
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use*; D011994:Recombinant Proteins
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D019259:Lamivudine; D011092:Polyethylene Glycols; D000410:Alanine Transaminase; C100416:peginterferon alfa-2a