Intrahepatic response markers in chronic hepatitis B patients treated with peginterferon alpha-2a and adefovir

J Gastroenterol Hepatol. 2011 Oct;26(10):1527-35. doi: 10.1111/j.1440-1746.2011.06766.x.


Background and aim: 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.

Publication types

  • Clinical Trial

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / therapeutic use
  • Adult
  • Antiviral Agents / therapeutic use*
  • Biomarkers / analysis
  • Biopsy
  • Chi-Square Distribution
  • DNA, Circular / analysis*
  • DNA, Viral / analysis*
  • Drug Therapy, Combination
  • Female
  • Hepatitis B Core Antigens / analysis
  • Hepatitis B Surface Antigens / analysis
  • Hepatitis B e Antigens / analysis
  • Hepatitis B virus / drug effects*
  • Hepatitis B virus / genetics
  • Hepatitis B virus / immunology
  • Hepatitis B, Chronic / diagnosis
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / virology
  • Humans
  • Immunohistochemistry
  • Interferon-alpha / therapeutic use*
  • Liver / drug effects*
  • Liver / pathology
  • Liver / virology
  • Male
  • Middle Aged
  • Netherlands
  • Organophosphonates / therapeutic use*
  • Polyethylene Glycols / therapeutic use*
  • Polymerase Chain Reaction
  • Predictive Value of Tests
  • Recombinant Proteins / therapeutic use
  • Time Factors
  • Treatment Outcome
  • Viral Load


  • Antiviral Agents
  • Biomarkers
  • DNA, Circular
  • DNA, Viral
  • Hepatitis B Core Antigens
  • Hepatitis B Surface Antigens
  • Hepatitis B e Antigens
  • Interferon-alpha
  • Organophosphonates
  • Recombinant Proteins
  • Polyethylene Glycols
  • adefovir
  • Adenine
  • peginterferon alfa-2a

Associated data

  • ISRCTN/ISRCTN77073364