Serum hepatitis B surface antigen quantitation can reflect hepatitis B virus in the liver and predict treatment response.
OBJECTIVE
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.
Department of Medicine and Therapeutics, and Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China. hlychan@cuhk.edu.hk
Henry Lik-Yuen
HL
Chan
Vincent Wai-Sun
VW
Wong
Ada Mei-Ling
AM
Tse
Chi-Hang
CH
Tse
Angel Mei-Ling
AM
Chim
Hoi-Yun
HY
Chan
Grace Lai-Hung
GL
Wong
Joseph Jao-Yiu
JJ
Sung
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D001706:Biopsy; D004279:DNA, Viral / Q000032:analysis; D004337:Drug Carriers; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006514:Hepatitis B Surface Antigens / Q000032:analysis* / Q000187:drug effects; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D019259:Lamivudine / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology / Q000821:virology*; D008297:Male; D011092:Polyethylene Glycols; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
D000998:Antiviral Agents; D004279:DNA, Viral; D004337:Drug Carriers; D006514:Hepatitis B Surface Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b