Document Detail

Intrahepatic response markers in chronic hepatitis B patients treated with peginterferon alpha-2a and adefovir.
MedLine Citation:
PMID:  21557773     Owner:  NLM     Status:  MEDLINE    
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.
Bart Takkenberg; Valeska Terpstra; Hans Zaaijer; Christine Weegink; Marcel Dijkgraaf; Peter Jansen; Marcel Beld; Hendrik Reesink
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Publication Detail:
Type:  Clinical Trial; Journal Article    
Journal Detail:
Title:  Journal of gastroenterology and hepatology     Volume:  26     ISSN:  1440-1746     ISO Abbreviation:  J. Gastroenterol. Hepatol.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-09-28     Completed Date:  2012-01-23     Revised Date:  2013-05-24    
Medline Journal Info:
Nlm Unique ID:  8607909     Medline TA:  J Gastroenterol Hepatol     Country:  Australia    
Other Details:
Languages:  eng     Pagination:  1527-35     Citation Subset:  IM    
Copyright Information:
© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.
Departments of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
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MeSH Terms
Adenine / analogs & derivatives*,  therapeutic use
Antiviral Agents / therapeutic use*
Biological Markers / analysis
Chi-Square Distribution
DNA, Circular / analysis*
DNA, Viral / analysis*
Drug Therapy, Combination
Hepatitis B Core Antigens / analysis
Hepatitis B Surface Antigens / analysis
Hepatitis B e Antigens / analysis
Hepatitis B virus / drug effects*,  genetics,  immunology
Hepatitis B, Chronic / diagnosis,  drug therapy*,  virology
Interferon-alpha / therapeutic use*
Liver / drug effects*,  pathology,  virology
Middle Aged
Organophosphonates / therapeutic use*
Polyethylene Glycols / therapeutic use*
Polymerase Chain Reaction
Predictive Value of Tests
Recombinant Proteins / therapeutic use
Time Factors
Treatment Outcome
Viral Load
Reg. No./Substance:
0/Antiviral Agents; 0/Biological Markers; 0/DNA, Circular; 0/DNA, Viral; 0/Hepatitis B Core Antigens; 0/Hepatitis B Surface Antigens; 0/Hepatitis B e Antigens; 0/Interferon-alpha; 0/Organophosphonates; 0/Polyethylene Glycols; 0/Recombinant Proteins; 0/peginterferon alfa-2a; 6GQP90I798/adefovir; 73-24-5/Adenine

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