title: Intrahepatic response markers in chronic hepatitis B patients treated with peginterferon alpha-2a and adefovir.
abstract: OBJECTIVE
  We investigated whether intrahepatic markers could predict response in chronic hepatitis B virus (HBV) patients treated with peg-interferon and adefovir for 48 weeks.
  
  
  METHODS
  Intrahepatic covalently closed circular DNA (cccDNA), total intrahepatic HBV DNA and the proportion of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) positive hepatocytes in 16 hepatitis B e antigen (HBeAg) positive and 24 HBeAg negative patients were measured at baseline and at end of treatment.
  
  
  RESULTS
  Baseline intrahepatic markers were not associated with sustained virological response (SVR) defined as HBV DNA < 2000 IU/mL and persistent normal alanine aminotransferase levels at the end of follow-up (week 72). At end of treatment, intrahepatic cccDNA and total intrahepatic HBV DNA in HBeAg positive patients were significantly lower in patients with HBeAg seroconversion (P = 0.016 and P = 0.010) with positive predictive values (PPV) for SVR of 80% and 80%, respectively. In HBeAg negative patients, intrahepatic cccDNA and total intrahepatic HBV DNA had declined significantly at end of treatment (P = 0.035 and P = 0.041) and corresponding PPV for SVR was 73% and 82%. In HBeAg positive patients, median proportion of HBcAg positive hepatocytes declined significantly (P = 0.002) at end of treatment. In HBeAg negative patients, the proportion of HBsAg positive hepatocytes had declined significantly at end of treatment (P = 0.0009). Using HBsAg ≤ 7.5% as a limit, PPV for SVR in HBeAg negative patients was 83%.
  
  
  CONCLUSIONS
  At end of treatment in HBeAg positive patients, intrahepatic cccDNA and total intrahepatic HBV DNA were predictive for SVR. In HBeAg negative patients a proportion of < 7.5% HBsAg positive hepatocytes at end of treatment was a strong predictor for SVR.
authors.affiliation: Departments of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Bart
authors.initials: B
authors.lastname: Takkenberg
authors.forename: Valeska
authors.initials: V
authors.lastname: Terpstra
authors.forename: Hans
authors.initials: H
authors.lastname: Zaaijer
authors.forename: Christine
authors.initials: C
authors.lastname: Weegink
authors.forename: Marcel
authors.initials: M
authors.lastname: Dijkgraaf
authors.forename: Peter
authors.initials: P
authors.lastname: Jansen
authors.forename: Marcel
authors.initials: M
authors.lastname: Beld
authors.forename: Hendrik
authors.initials: H
authors.lastname: Reesink
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D016009:Chi-Square Distribution; D004270:DNA, Circular / Q000032:analysis*; D004279:DNA, Viral / Q000032:analysis*; D004359:Drug Therapy, Combination; D005260:Female; D006512:Hepatitis B Core Antigens / Q000032:analysis; D006514:Hepatitis B Surface Antigens / Q000032:analysis; D006513:Hepatitis B e Antigens / Q000032:analysis; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007150:Immunohistochemistry; D016898:Interferon-alpha / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D063065:Organophosphonates / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011994:Recombinant Proteins / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
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; D016898:Interferon-alpha; D063065:Organophosphonates; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C053001:adefovir; D000225:Adenine; C100416:peginterferon alfa-2a