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Intrahepatic response markers in chronic hepatitis B patients treated with peginterferon alpha‐2a and adefovir
Author(s) -
Takkenberg Bart,
Terpstra Valeska,
Zaaijer Hans,
Weegink Christine,
Dijkgraaf Marcel,
Jansen Peter,
Beld Marcel,
Reesink Hendrik
Publication year - 2011
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.2011.06766.x
Subject(s) - adefovir , cccdna , hbcag , medicine , hbeag , hbsag , gastroenterology , hepatitis b virus , alanine transaminase , entecavir , hepatitis b , immunology , virology , virus , lamivudine
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.