title: Response to interferon alfa is hepatitis B virus genotype dependent: genotype A is more sensitive to interferon than genotype D.
abstract: OBJECTIVE
  Current interferon alfa (IFN) treatment of chronic hepatitis B has limited efficacy. The role of hepatitis B virus (HBV) genotypes for response to IFN was investigated.
  
  
  METHODS
  HBV genotype was determined by direct sequencing of the HBV X gene in 165 consecutive patients with chronic replicative hepatitis B treated with standard IFN. HBV genotype A or D was found in 144 cases.
  
  
  RESULTS
  Sustained response (six months after treatment) to standard IFN therapy was higher in HBV genotype A compared with HBV genotype D infected patients (49% v 26%; p<0.005). Sustained response to IFN was 46% versus 24% (p<0.03) in hepatitis B e antigen (HBeAg) positive hepatitis (n = 99) and 59% versus 29% (p<0.05) in HBeAg negative hepatitis (n = 45) for HBV genotype A compared with HBV genotype D. HBeAg status had no negative impact on IFN response. Multivariate logistic regression identified HBV genotype A and high pretreatment alanine aminotransferase levels (>2 x upper limit of normal) as independent positive predictive parameters of IFN response.
  
  
  CONCLUSIONS
  The present study indicates that HBV genotypes A and D are important and independent predictors of IFN responsiveness in chronic hepatitis B. HBV genotype adapted treatment regimens may further improve treatment efficacy in chronic hepatitis B.
authors.affiliation: Klinik für Gastroenterologie, Hepatologie und Infektiologie, Heinrich-Heine-Universität Düsseldorf, Moorenstr 5, D-40225 Düsseldorf, Germany. erhardt@uni-duesseldorf.de
authors.forename: A
authors.initials: A
authors.lastname: Erhardt
authors.forename: D
authors.initials: D
authors.lastname: Blondin
authors.forename: K
authors.initials: K
authors.lastname: Hauck
authors.forename: A
authors.initials: A
authors.lastname: Sagir
authors.forename: T
authors.initials: T
authors.lastname: Kohnle
authors.forename: T
authors.initials: T
authors.lastname: Heintges
authors.forename: D
authors.initials: D
authors.lastname: Häussinger
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D013045:Species Specificity; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins