Reduction of hepatitis B core related antigen by long term nucleoside nucleotide analogue therapy and its correlation with intrahepatic HBV DNA reduction

Abstract

OBJECTIVE: We aimed to investigate the reduction of hepatitis B corerelated antigen (HBcrAg) in patients with long term nucleoside/ nucleotide analogue (NA) therapy. METHODS: Forty-three patients (median age: 43 years, range: 24–63 years) who had been on continuous (median follow-up duration: 10 years; range 5–12 years) NA therapy, including lamivudine, adefovir, telbivudine, entecavir, and tenofovir, were recruited. All patients had liver biopsies at baseline and at the last follow-up. HBcrAg (detection limit: 3 log U/mL) were measured using a Lumipulse HBcrAg assay (Fujirebio, Japan). Intrahepatic total HBV DNA (ihHBV-DNA) and covalently closed circular DNA (cccDNA) were assayed by real-time PCR. RESULTS: At baseline, the median levels of HBcrAg, ihHBV-DNA, and cccDNA were 6.7 log U/mL, 286 copies/cell, and 7.3 copies/cell, respectively. Baseline level of HBcrAg correlated positively with that of ihHBV-DNA (r = 0.568, P\0.0001), and cccDNA (r = 0.559, P\0.0001). At the time of last biopsy, 12 (28 %) patients had undetectable HBcrAg (median: 3.8; range:\3–5.7 log U/mL). All patients had detectable ihHBV-DNA (median: 0.35 copies/cell), and 21 (49 %) patients had undetectable cccDNA. The median logarithmic reductions of HBcrAg, ihHBV-DNA, and cccDNA were 2.7 log U/mL, 2.81 log copies/cell, and 2.94 log copies/cell, respectively. There was a positive correlation between the logarithmic reduction of HBcrAg and ihHBV-DNA (r = 0.550, P\0.001) and cccDNA (r = 0.419, P = 0.005). CONCLUSION: The marked reduction of HBcrAg, together with the reduction in ihHBV-DNA and cccDNA, further supports the effectiveness of long-term nucleoside/tide analogue therapy in potentially eradicating HBV from chronic carriers