Detection of hepatitis B virus core-related antigens as a marker for the monitoring of viral activity during nucleoside analogue therapy

Abstract

BACKGROUND: Our previous study has shown that serum hepatitis B corerelated antigen (HBcrAg) concentration correlates positively with serum and intrahepatic total HBV DNA, cccDNA, as well as liver histology (Wong et al, Hepatology 2005; 42:712A). This study aimed to investigate the use of serum HBcrAg measurement to monitor viral activity during nucleoside analogue therapy. PATIENTS AND METHODS: Thirty-nine chronic hepatitis B patients were randomized to receive daily doses of either 0.5 mg entecavir (N 20) or 100mg lamivudine (N 19) for one year. Serum and liver biopsy samples were collected at baseline, week 24 and week 48 of treatment. Total intrahepatic HBV DNA and cccDNA were measured by the Invader assay. Serum HBcrAg was detected by a chemiluminescence enzyme immunoassay as described previously (Kimura et al, J Clin Microbiol 2002; 40:439M45). RESULTS: There was a positive correlation between the baseline HBcrAg levels and baseline serum HBV DNA levels (r 0.767, p < 0.001), baseline intrahepatic total HBV DNA (r 0.510, p 0.001) and baseline cccDNA levels (r 0.514, p 0.001). At baseline, there was no significant difference between entecavir- and lamivudine-treated patients in terms of median serum HBV DNA (1.9• vs. 1.9• copies/mL), median intrahepatic total HBV DNA (34.6 vs. 42.0copies/cell), median cccDNA (1.3 vs. 1.9copies/cell), and median HBcrAg levels (1380 vs. 2850kU/mL) (all p NS). Upon 48 weeks of antiviral therapy of all 39 patients, HBcrAg levels decreased by a median of 1.41og10 kU/mL (range: 1.2 3.6 logl0 kU/mL). Logarithmic reduction of HBcrAg levels at week 48 of treatment correlated positively with the logarithmic reduction in serum HBV DNA (r 0.576, p 2 points had a greater reduction in HBcrAg concentration than patients with no or little improvement (p 0.031). There was a negative correlation between the logarithmic reduction of serum HBcrAg concentration and percentage of hepatocytes stained positive for cytoplasmic hepatitis B core antigen (p 0.017) and nuclear hepatitis B core antigen (p 0.007). CONCLUSION: Serum HBcrAg measurement can be used as an alternative viral marker for disease monitoring during nucleoside analogue therapy.