title: Successful treatment with peginterferon alfa-2b of HBeAg-positive HBV non-responders to standard interferon or lamivudine.
abstract: OBJECTIVE
  Antiviral therapy leads to HBeAg seroconversion in 10-40% of the patients with HBeAg-positive chronic hepatitis B. Nonresponse may result in progression of liver disease and increased risk of hepatocellular carcinoma. As part of a global randomized controlled trial we investigated the efficacy (i.e., loss of HBeAg at the end of follow-up) of peginterferon alfa-2b (Peg-IFN alpha2b) in patients who failed to respond to previous courses of standard interferon (IFN) or lamivudine.
  
  
  METHODS
  We analyzed a total of 76 previous nonresponders: 37 were nonresponders to standard IFN, 17 were nonresponders to lamivudine, and 22 were nonresponders to both therapies. All patients received a 52-wks course of 100 microg Peg-IFN alpha2b weekly combined with either 100 mg lamivudine daily or a placebo. After therapy patients were followed for 26 wks.
  
  
  RESULTS
  Thirteen (35%) nonresponders to previous IFN, five (29%) nonresponders to previous lamivudine, and four (22%) nonresponders to both IFN and lamivudine responded to treatment with Peg-IFN alpha2b. No difference in response was found for those treated with Peg-IFN alpha2b alone or in combination with lamivudine. Nonresponders to prior IFN therapy with baseline ALT (alanine aminotransferase) > 4 x ULN (upper limit of normal) responded better to Peg-IFN alpha2b than those with ALT levels <or= 4 x ULN (53%vs 20%, respectively, p= 0.036).
  
  
  CONCLUSIONS
  Peg-IFN alpha2b is effective in approximately one-third of patients who failed to respond to previous treatment with standard IFN or lamivudine. High serum ALT level at baseline of Peg-IFN alpha2b therapy was the best predictor for response in these patients.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Hajo J
authors.initials: HJ
authors.lastname: Flink
authors.forename: Bettina E
authors.initials: BE
authors.lastname: Hansen
authors.forename: E Jenny
authors.initials: EJ
authors.lastname: Heathcote
authors.forename: S Victor
authors.initials: SV
authors.lastname: Feinman
authors.forename: Halis
authors.initials: H
authors.lastname: Simsek
authors.forename: Selim
authors.initials: S
authors.lastname: Karayalcin
authors.forename: Tomasz
authors.initials: T
authors.lastname: Mach
authors.forename: Wim F
authors.initials: WF
authors.lastname: Leemans
authors.forename: Robert A
authors.initials: RA
authors.lastname: de Man
authors.forename: Elke
authors.initials: E
authors.lastname: Verhey
authors.forename: Solko W
authors.initials: SW
authors.lastname: Schalm
authors.forename: Harry L A
authors.initials: HL
authors.lastname: Janssen
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006513:Hepatitis B e Antigens / Q000032:analysis*; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D007372:Interferons / Q000627:therapeutic use; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D011092:Polyethylene Glycols; D011994:Recombinant Proteins
chemical_list: D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D019259:Lamivudine; D011092:Polyethylene Glycols; D007372:Interferons; C417083:peginterferon alfa-2b