Abstract
Background
This study investigated the effect of nucleos(t)ide analogues (NUC) treatment on HBV DNA integration and hepatocyte clonal expansion, both of which are implicated in hepatocellular carcinoma (HCC) in chronic hepatitis B.
Methods
Twenty-eight patients receiving NUCs (11 lamivudine, 7 telbivudine, 10 entecavir) were included. All had liver biopsies at baseline and year 1, and seven had a third biopsy at year 10. HBV DNA integration and hepatocyte clone size were assessed by inverse PCR.
Results
All patients had detectable HBV integration at baseline, with a median integration frequency of 1.01×10
9 per liver and hepatocyte clone size of 2.41×10
5. Neither integration frequency nor hepatocyte clone size correlated with age and HBV virologic parameters. After one year of treatment, HBV integration was still detectable in all patients, with a median of 5.74×10
8 integration per li ver (0.22 log reduction;
P = .008) and hepatocyte clone size of 1.22×10
5 (0.40 log reduction;
P = .002). HBV integration remained detectable at year 10 of treatment, with a median integration frequency of 4.84×10
7 integration per liver (0.93 log reduction from baseline) and hepatocyte clone size of 2.55×10
4 (1.02 log reduction from baseline). From baseline through year 1 to year 10, there was a decreasing trend in both integration frequency and hepatocyte clone size (
P = .066 and.018, respectively).
Conclusions
NUCs reduced both HBV DNA integration and hepatocyte clonal expansion, suggesting another alternative pathway besides direct viral suppression to reduce HCC risk. Our findings supported the notion for a long-term NUC treatment to prevent HCC.
No comments:
Post a Comment