title: Response-guided peginterferon therapy in hepatitis B e antigen-positive chronic hepatitis B using serum hepatitis B surface antigen levels.
abstract: On-treatment levels of hepatitis B surface antigen (HBsAg) may predict response to peginterferon (PEG-IFN) therapy in chronic hepatitis B (CHB), but previously proposed prediction rules have shown limited external validity. We analyzed 803 HBeAg-positive patients treated with PEG-IFN in three global studies with available HBsAg measurements. A stopping-rule based on absence of a decline from baseline was compared to a prediction-rule that uses HBsAg levels of <1,500 IU/mL and >20,000 IU/mL to identify patients with high and low probabilities of response. Patients with an HBsAg level <1,500 IU/mL at week 12 achieved response (HBeAg loss with HBV DNA <2,000 IU/mL at 6 months posttreatment) in 45%. At week 12, patients without a decline in HBsAg achieved a response in 14%, compared to only 6% of patients with HBsAg >20,000 IU/mL, but performance varied across HBV genotype. In patients treated with PEG-IFN monotherapy (n = 465), response rates were low in patients with genotypes A or D if there was no decline of HBsAg by week 12 (negative predictive value [NPV]: 97%-100%), and in patients with genotypes B or C if HBsAg at week 12 was >20,000 IU/mL (NPV: 92%-98%). At week 24, nearly all patients with HBsAg >20,000 IU/mL failed to achieve a response, irrespective of HBV genotype (NPV for response and HBsAg loss 99% and 100%).
  
  
  CONCLUSIONS
  HBsAg is a strong predictor of response to PEG-IFN in HBeAg-positive CHB. HBV genotype-specific stopping-rules may be considered at week 12, but treatment discontinuation is indicated in all patients with HBsAg >20,000 IU/mL at week 24, irrespective of HBV genotype.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: Milan J
authors.initials: MJ
authors.lastname: Sonneveld
authors.forename: Bettina E
authors.initials: BE
authors.lastname: Hansen
authors.forename: Teerha
authors.initials: T
authors.lastname: Piratvisuth
authors.forename: Ji-Dong
authors.initials: JD
authors.lastname: Jia
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.forename: Edward
authors.initials: E
authors.lastname: Gane
authors.forename: Yun-Fan
authors.initials: YF
authors.lastname: Liaw
authors.forename: Qing
authors.initials: Q
authors.lastname: Xie
authors.forename: E Jenny
authors.initials: EJ
authors.lastname: Heathcote
authors.forename: Henry L-Y
authors.initials: HL
authors.lastname: Chan
authors.forename: Harry L A
authors.initials: HL
authors.lastname: Janssen
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D011994:Recombinant Proteins / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a