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.


METHODS
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 x 10(6) 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.
Yuen
Man-Fung
MF
Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.
Wong
Danny Ka-Ho
DK
Sum
Simon Siu-Man
SS
Yuan
He-Jun
HJ
Yuen
John Chi-Hang
JC
Chan
Annie On-On
AO
Wong
Benjamin Chun-Yu
BC
Lai
Ching-Lung
CL
D000293:Adolescent; D000328:Adult; D020816:Amino Acid Motifs / Q000187:drug effects / Q000235:genetics; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D001224:Aspartic Acid / Q000187:drug effects / Q000235:genetics; D004270:DNA, Circular / Q000097:blood / Q000187:drug effects*; D004279:DNA, Viral / Q000097:blood / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D007532:Isoleucine / Q000235:genetics; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008715:Methionine / Q000187:drug effects / Q000235:genetics; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010919:Placebos; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D014443:Tyrosine / Q000187:drug effects / Q000235:genetics; D014633:Valine / Q000235:genetics; D019562:Viral Load
D019380:Anti-HIV Agents; D004270:DNA, Circular; D004279:DNA, Viral; D010919:Placebos; D018894:Reverse Transcriptase Inhibitors; D007532:Isoleucine; D019259:Lamivudine; D001224:Aspartic Acid; D014443:Tyrosine; D008715:Methionine; D014633:Valine