title: Hepatitis B e antigen levels and response to peginterferon: influence of precore and basal core promoter mutants.
abstract: Hepatitis B e antigen (HBeAg) levels may predict response to peginterferon (PEG-IFN) but are also influenced by presence of precore (PC) and core promoter (BCP) mutants. HBeAg was measured in 214 patients treated with PEG-IFN±lamivudine for 52weeks. Patients were classified at baseline as wildtype (WT) or non-WT (detectable PC/BCP mutants). Combined response (HBeAg loss with HBV DNA<2000IU/mL), HBeAg response (HBeAg loss with HBV DNA>2000IU/mL) or non-response was assessed at week78. Mean baseline HBeAg levels were 2.65logIU/mL in combined responders, 2.48 in non-responders and 2.24 in HBeAg responders (p=0.034). Baseline HBeAg levels were not associated with combined response after stratification by WT/non-WT. Within the PEG-IFN monotherapy group (n=104), patients with HBeAg<1logIU/mL at week24 had a higher probability of combined response (29% versus 12%, p=0.041). After stratification by WT/non-WT, WT patients with HBeAg<1logIU/mL at week24 had a probability of combined response of 78% (versus 19% in patients with >1logIU/mL, p<0.001), whereas no difference in response rates was observed in non-WT patients (p=0.848). The relationship between HBeAg levels and response to PEG-IFN depends upon the presence of PC/BCP mutants. HBeAg levels should therefore not be routinely used to select patients for PEG-IFN, nor for monitoring of therapy.
authors.affiliation: Departments of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands. j.sonneveld@erasmusmc.nl
authors.forename: Milan J
authors.initials: MJ
authors.lastname: Sonneveld
authors.forename: Vincent
authors.initials: V
authors.lastname: Rijckborst
authors.forename: Louwerens
authors.initials: L
authors.lastname: Zwang
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.forename: E
authors.initials: E
authors.lastname: Jenny Heathcote
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Simon
authors.forename: Roeland
authors.initials: R
authors.lastname: Zoutendijk
authors.forename: Ulus S
authors.initials: US
authors.lastname: Akarca
authors.forename: Suzan D
authors.initials: SD
authors.lastname: Pas
authors.forename: Bettina E
authors.initials: BE
authors.lastname: Hansen
authors.forename: Harry L A
authors.initials: HL
authors.lastname: Janssen
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000187:drug effects; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D011994:Recombinant Proteins / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b