BACKGROUND & AIMS: We aimed to evaluate serum hepatitis B surface antigen (HBsAg) quantitation as a surrogate marker for covalently closed circular DNA (cccDNA) and intrahepatic hepatitis B virus (HBV) DNA, and as a predictor of sustained virologic response to peginterferon and lamivudine combination therapy. METHODS:Twenty-six hepatitis B e antigen-positive chronic hepatitis B patients receiving combination treatment of 32-weekpeginterferon alfa-2b and 2-year lamivudine were studied. All patients had liver biopsy before and after treatment for cccDNA and intrahepatic HBV DNA measurement. Sustained virologic response was defined as sustained hepatitis B e antigen seroconversion and HBV DNA less than 10,000 copies/mL at the end of treatment until 1 year posttreatment. RESULTS: Seven patients developed sustained virologic response. At baseline, HBsAg correlated well with both log (cccDNA) (r = 0.54, P = .004) and log [total intrahepatic HBV DNA] (r = 0.43, P = .028). The median reduction of HBsAg was 1287 IU/mL (range, 12,223-26,763 IU/mL). Reduction of HBsAg has good correlation with reduction in log [cccDNA] (r = 0.68, P < .0001) and reduction in log [total intrahepatic HBV DNA] (r = 0.65, P < .0001). Patients with lower baseline cccDNA, intrahepatic HBV DNA, and HBsAg level but not serum HBV DNA level tend to develop sustained virologic response. A baseline HBsAg level of less than 10,000 IU/mL had sensitivity, specificity, and positive and negative predictive values for sustained virologic response of 86%, 56%, 43%, and 92%, respectively. CONCLUSIONS:Serum HBsAg levels correlate well with the cccDNA and intrahepatic HBV DNA. Low pretreatment HBsAg is better than HBV DNA to predict good response to peginterferon and lamivudine treatment.
RCT Entities:
BACKGROUND & AIMS: We aimed to evaluate serum hepatitis B surface antigen (HBsAg) quantitation as a surrogate marker for covalently closed circular DNA (cccDNA) and intrahepatic hepatitis B virus (HBV) DNA, and as a predictor of sustained virologic response to peginterferon and lamivudine combination therapy. METHODS: Twenty-six hepatitis B e antigen-positive chronic hepatitis B patients receiving combination treatment of 32-week peginterferon alfa-2b and 2-year lamivudine were studied. All patients had liver biopsy before and after treatment for cccDNA and intrahepatic HBV DNA measurement. Sustained virologic response was defined as sustained hepatitis B e antigen seroconversion and HBV DNA less than 10,000 copies/mL at the end of treatment until 1 year posttreatment. RESULTS: Seven patients developed sustained virologic response. At baseline, HBsAg correlated well with both log (cccDNA) (r = 0.54, P = .004) and log [total intrahepatic HBV DNA] (r = 0.43, P = .028). The median reduction of HBsAg was 1287 IU/mL (range, 12,223-26,763 IU/mL). Reduction of HBsAg has good correlation with reduction in log [cccDNA] (r = 0.68, P < .0001) and reduction in log [total intrahepatic HBV DNA] (r = 0.65, P < .0001). Patients with lower baseline cccDNA, intrahepatic HBV DNA, and HBsAg level but not serum HBV DNA level tend to develop sustained virologic response. A baseline HBsAg level of less than 10,000 IU/mL had sensitivity, specificity, and positive and negative predictive values for sustained virologic response of 86%, 56%, 43%, and 92%, respectively. CONCLUSIONS: Serum HBsAg levels correlate well with the cccDNA and intrahepatic HBV DNA. Low pretreatment HBsAg is better than HBV DNA to predict good response to peginterferon and lamivudine treatment.
Authors: Christine I Wooddell; Man-Fung Yuen; Henry Lik-Yuen Chan; Robert G Gish; Stephen A Locarnini; Deborah Chavez; Carlo Ferrari; Bruce D Given; James Hamilton; Steven B Kanner; Ching-Lung Lai; Johnson Y N Lau; Thomas Schluep; Zhao Xu; Robert E Lanford; David L Lewis Journal: Sci Transl Med Date: 2017-09-27 Impact factor: 17.956
Authors: Sang Hoon Ahn; Henry L Y Chan; Pei-Jer Chen; Jun Cheng; Mahesh K Goenka; Jinlin Hou; Seng Gee Lim; Masao Omata; Teerha Piratvisuth; Qing Xie; Hyung Joon Yim; Man-Fung Yuen Journal: Hepatol Int Date: 2010-02-20 Impact factor: 6.047