Effect of Lamivudine Therapy on the Serum Covalently Closed-Circular (ccc) DNA of Chronic Hepatitis B Infection

OBJECTIVE:To determine the effect of 1-yr lamivudine treatment on serum covalently closed-circular DNA (cccDNA) level.PATIENTS AND METHOD:Serum total HBV DNA and cccDNA levels at baseline, week 24, and week 52 were measured in 82 lamivudine-treated patients, 17 of whom received 1-yr placebo and acted as controls.RESULTS:There was a significant reduction in the cccDNA levels from baseline (median 3.0 × 106 copies/ml) to week 24 (33,476 copies/ml) and week 52 (48,694 copies/ml) (p < 0.001 for both). The median reduction in cccDNA level at week 24 and 52 were 2.21 and 2.12 logs, respectively, which were significantly greater than those of controls (0.31 log, p < 0.001; 0.2 log, p < 0.001, respectively). Fifteen patients (18.3%) developed YMDD mutations by week 52. Compared to patients without YMDD mutations, patients with YMDD mutations had significantly less median reduction of total HBV DNA level (4.44 vs 3.65 logs, respectively, p = 0.02) and cccDNA level (2.27 vs 1.65 logs, respectively, p = 0.016) at week 24 and significantly less median reduction of cccDNA at week 52 (2.35 vs 0.8 logs respectively, p < 0.001).CONCLUSIONS:One-year lamivudine treatment decreased serum cccDNA level by 2 logs. The chance of YMDD mutations at week 52 was related to the magnitude of viral suppression at week 24.