title: Serum hepatitis B core-related antigen as a treatment predictor of pegylated interferon in patients with HBeAg-positive chronic hepatitis B.
abstract: The role of quantitative serum hepatitis B core-related antigen (HBcrAg) in patients with chronic hepatitis B (CHB) receiving pegylated interferon (PEG-IFN) is unclear. This study was aimed at comparing its usefulness with quantitative HBsAg in patients with HBeAg-positive CHB receiving PEG-IFN therapy.
  
  
  
  A total 46 patients treated with PEG-IFN for 48 weeks were retrospectively analysed. Intrahepatic covalently closed circular DNA (cccDNA) from paired liver biopsies and serial serum HBsAg and HBcrAg during therapy were assessed.
  
  
  
  Virological response (VR), defined as HBeAg clearance and HBV DNA <2000 IU/ml at 24 weeks post treatment, was achieved in 15 (32.6%) patients. Responders had significantly higher cccDNA decline from baseline compared with non-responders. Baseline HBsAg and HBcrAg were correlated with cccDNA (r = 0.424, P = 0.020 and r = 0.564, P = 0.001, respectively), and changes in the corresponding markers during therapy were correlated with cccDNA reduction (r = 0.579, P = 0.001 and r = 0.503, P = 0.005, respectively). Responders showed more rapid decline of both markers during therapy compared with non-responders. In multivariate analysis, serum HBcrAg at week 12 was identified as a predictor of VR. The optimal cut-off value for HBcrAg (log10 8.0 U/ml) provided negative predictive value (NPV) of achieving VR at weeks 12 and 24 of 94.4 and 100%, respectively, while using HBsAg > 20 000 IU/ml provided NPV of 80 and 100% respectively.
  
  
  
  The convenient quantitative HBcrAg represented a reliable marker of intrahepatic cccDNA. Monitoring HBcrAg levels during PEG-IFN therapy may help identify patients with a very low probability of response comparable to, if not better than, quantitative HBsAg.
authors.affiliation: Research Unit of Hepatitis and Liver Cancer, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Natthaya
authors.initials: N
authors.lastname: Chuaypen
authors.affiliation: Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Nawarat
authors.initials: N
authors.lastname: Posuwan
authors.affiliation: Research Unit of Hepatitis and Liver Cancer, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Sunchai
authors.initials: S
authors.lastname: Payungporn
authors.affiliation: Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Shinkai
authors.affiliation: Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Yong
authors.initials: Y
authors.lastname: Poovorawan
authors.affiliation: Research Unit of Hepatitis and Liver Cancer, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Pisit
authors.initials: P
authors.lastname: Tangkijvanich
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D004270:DNA, Circular / Q000032:analysis; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006512:Hepatitis B Core Antigens / Q000097:blood*; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D012372:ROC Curve; D000072230:Sustained Virologic Response; D013785:Thailand
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D004270:DNA, Circular; D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D007372:Interferons
keywords: HBsAg quantification; hepatitis B core-related antigen; hepatitis B virus; pegylated interferon