title: Effect of host and viral factors on hepatitis B e antigen-positive chronic hepatitis B patients receiving pegylated interferon-α-2a therapy.
abstract: BACKGROUND
  Pegylated interferon (PEG-IFN)-α-2a improves the hepatitis B e antigen (HBeAg) seroconversion rate in HBeAg-positive chronic hepatitis B patients. However, baseline factors predicting favourable responses to PEG-IFN-α-2a remain largely unknown.
  
  
  METHODS
  A total of 115 HBeAg-positive chronic hepatitis B patients who had a pre-therapy serum alanine aminotransferase (ALT) level over two times the upper limit of normal and received PEG-IFN-α-2a for 6-12 months were consecutively enrolled according to the local reimbursed guidelines. HBeAg seroconversion and combined response defined as HBeAg seroconversion, HBV-DNA level <20,000 IU/ml as well as ALT normalization at 6 months off therapy were primary and secondary therapeutic end points, respectively. Baseline viral factors, including viral load, genotype and major sequences of precore stop codon/basal core promoter (BCP), and host factors, including three single nucleotide polymorphisms among the HLA-DPA1, HLA-DPB1 and IL28B regions, were determined to correlate with therapeutic end points.
  
  
  RESULTS
  HBeAg seroconversion and combined response rates were 26.1% and 18.3%, respectively. By multivariate analysis, BCP mutation (OR 8.04, 95% CI 2.00-32.28) and rs3077 G/G genotype (OR 3.49, 95% CI 1.12-10.84) were associated with a higher HBeAg seroconversion rate; BCP mutation (OR 9.28, 95% CI 1.92-44.99) and baseline viral load <2 × 10(6) IU/ml (OR 4.78, 95% CI 1.37-16.69) were associated with a higher combined response rate.
  
  
  CONCLUSIONS
  BCP mutation is associated with higher HBeAg seroconversion and combined response rates at 6 months off therapy in HBeAg-positive chronic hepatitis B patients treated with PEG-IFN-α-2a. Genetic variants in the HLA-DPA1 region may also affect treatment-induced HBeAg seroconversion.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Buddhist Tzu-Chi General Hospital Taipei Branch, Taipei, Taiwan.
authors.forename: Tai-Chung
authors.initials: TC
authors.lastname: Tseng
authors.forename: Ming-Lung
authors.initials: ML
authors.lastname: Yu
authors.forename: Chun-Jen
authors.initials: CJ
authors.lastname: Liu
authors.forename: Chih-Lin
authors.initials: CL
authors.lastname: Lin
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Huang
authors.forename: Ching-Sheng
authors.initials: CS
authors.lastname: Hsu
authors.forename: Chen-Hua
authors.initials: CH
authors.lastname: Liu
authors.forename: Stephanie Fang-Tzu
authors.initials: SF
authors.lastname: Kuo
authors.forename: Corinna Jen-Hui
authors.initials: CJ
authors.lastname: Pan
authors.forename: Sheng-Shun
authors.initials: SS
authors.lastname: Yang
authors.forename: Chien-Wei
authors.initials: CW
authors.lastname: Su
authors.forename: Pei-Jer
authors.initials: PJ
authors.lastname: Chen
authors.forename: Ding-Shinn
authors.initials: DS
authors.lastname: Chen
authors.forename: Jia-Horng
authors.initials: JH
authors.lastname: Kao
mesh_terms: D000998:Antiviral Agents / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood / Q000276:immunology; D005260:Female; D059867:HLA-DP alpha-Chains / Q000235:genetics / Q000276:immunology; D059868:HLA-DP beta-Chains / Q000235:genetics / Q000276:immunology; D006513:Hepatitis B e Antigens / Q000097:blood / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D006785:Hospitals, University; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D011092:Polyethylene Glycols / Q000494:pharmacology / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D059867:HLA-DP alpha-Chains; D059868:HLA-DP beta-Chains; C071172:HLA-DPA1 antigen; C071170:HLA-DPB1 antigen; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a