TY - JOUR
T1 - Intrahepatic response markers in chronic hepatitis B patients treated with peginterferon alpha-2a and adefovir
AU - Takkenberg, Bart
AU - Terpstra, Valeska
AU - Zaaijer, Hans
AU - Weegink, Christine
AU - Dijkgraaf, Marcel
AU - Jansen, Peter
AU - Beld, Marcel
AU - Reesink, Hendrik
PY - 2011
Y1 - 2011
N2 - We investigated whether intrahepatic markers could predict response in chronic hepatitis B virus (HBV) patients treated with peg-interferon and adefovir for 48 weeks. 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. 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%. 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
AB - We investigated whether intrahepatic markers could predict response in chronic hepatitis B virus (HBV) patients treated with peg-interferon and adefovir for 48 weeks. 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. 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%. 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
U2 - https://doi.org/10.1111/j.1440-1746.2011.06766.x
DO - https://doi.org/10.1111/j.1440-1746.2011.06766.x
M3 - Article
C2 - 21557773
SN - 0815-9319
VL - 26
SP - 1527
EP - 1535
JO - Journal of gastroenterology and hepatology
JF - Journal of gastroenterology and hepatology
IS - 10
ER -