title: Experimental HBsAg/anti-HBs complex assay for prediction of HBeAg loss in chronic hepatitis B patients treated with pegylated interferon and adefovir.
abstract: BACKGROUND
  We studied whether hepatitis B surface antigen (HBsAg)/anti-HBs immune complex levels in chronic hepatitis B (CHB) patients receiving antiviral therapy could be used as a response marker at baseline (BL) or early during treatment to predict treatment outcome.
  
  
  METHODS
  An experimental array-based assay (immunological multi-parameter chip technology [IMPACT]; Roche Diagnostics, Penzberg, Germany) served to determine HBsAg, anti-HBs and complex levels. We tested a panel of serum samples of 40 hepatitis B e antigen (HBeAg)-positive and 44 HBeAg-negative patients who received pegylated interferon and adefovir for 48 weeks.
  
  
  RESULTS
  HBsAg loss occurred in 4 of 40 HBeAg-positive and 4 of 44 HBeAg-negative patients. A total of 14 of 40 HBeAg-positive patients lost HBeAg and 12 of them formed anti-HBe. At BL, complexes were present in 83 (99%) patients, whereas free anti-HBs levels were detectable in 5 patients. Complex levels at BL and week 12 were higher in HBeAg-positive patients with HBeAg loss, compared to patients who retained HBeAg (P=0.002 and P=0.005, respectively). Receiver operating characteristic analysis for HBeAg loss in HBeAg-positive patients at BL and week 12 showed area-under-the-curve values of 0.79 (P=0.002) and 0.82 (P=0.003) for complex levels. We found no correlation in either HBeAg-positive or -negative patients between complex levels and HBsAg loss.
  
  
  CONCLUSIONS
  We demonstrated for the first time that before and during treatment HBsAg/anti-HBs immune complex levels can predict HBeAg loss in HBeAg-positive CHB patients treated with pegylated interferon and adefovir. Complexes were present in almost all patients at BL and were higher in patients who lost HBeAg. In conclusion, determining HBsAg/anti-HBs immune complex levels before and early during treatment could aid in selecting CHB patients with an optimal chance to achieve HBeAg loss.
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, the Netherlands. a.deniet@amc.nl.
authors.forename: Annikki
authors.initials: A
authors.lastname: de Niet
authors.forename: Louis
authors.initials: L
authors.lastname: Jansen
authors.forename: Hans L
authors.initials: HL
authors.lastname: Zaaijer
authors.forename: Ursula
authors.initials: U
authors.lastname: Klause
authors.forename: Bart
authors.initials: B
authors.lastname: Takkenberg
authors.forename: Harry L A
authors.initials: HL
authors.lastname: Janssen
authors.forename: Tom
authors.initials: T
authors.lastname: Chu
authors.forename: Rosemary
authors.initials: R
authors.lastname: Petric
authors.forename: Hendrik W
authors.initials: HW
authors.lastname: Reesink
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000936:Antigen-Antibody Complex / Q000097:blood*; D000998:Antiviral Agents / Q000627:therapeutic use*; D019540:Area Under Curve; D004279:DNA, Viral / Q000097:blood; D005260:Female; D006510:Hepatitis B Antibodies / Q000097:blood*; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000187:drug effects / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D040081:Protein Array Analysis; D011485:Protein Binding; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000936:Antigen-Antibody Complex; D000998:Antiviral Agents; D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha; D063065:Organophosphonates; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C053001:adefovir; D000225:Adenine; C100416:peginterferon alfa-2a