Infect Genet Evol. 2017 Jan 11. pii: S1567-1348(17)30012-6. doi: 10.1016/j.meegid.2017.01.009. [Epub ahead of print]
The nucleotide changes within HBV core promoter/precore during the first 12weeks of nucleos(t)ide treatment might be associated with a better virological response.Peng Y1, Li Y2, Hou J3, Sun J3, Su M2, Li Y2, Xiang K2, Yan L2, Zhuang H2, Li T4. Author information
1Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; Department of Clinical Laboratory, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
2Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
3Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
4Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China. Electronic address: [email protected].
AbstractOBJECTIVES: We aimed to study the dynamic changes of hepatitis B virus (HBV) core promoter/precore (CP/preC) sequences during antiviral treatment and their associations with virological responses.
MATERIALS AND METHODS: The baseline and 12-week CP/preC sequences (nts 1655-2014) were obtained from 52 chronic hepatitis B patients with positive hepatitis B e antigen (HBeAg), who received a 104-week lamivudine and adefovir dipivoxil combination therapy. The mutations within the CP/preC were analyzed against genotype specific reference sequences. The nucleotide change rates in individuals during therapy were analyzed in a pairwise comparison manner.
RESULTS: There was no significant difference of the mutation rate at each nucleotide site between baseline and week 12 of treatment (P>0.05). The mutation rates of A1762T/G1764A and G1896A were found to decrease from 46.2% (24/52) at baseline to 36.5% (19/52) at week 12 (P=0.426) and from 28.8% (15/52) to 21.2% (11/52) (P=0.497), respectively. The nucleotide change rates varied from 0.0% - 7.8% in individuals [0.0% in Group 1 (N=26); 0.3% - 7.8% in Group 2 (N=26)] during the first 12-week treatment. HBV DNA levels in group 2 were significantly lower than those in group 1 throughout therapy (P<0.01) (e.g., 1.5±1.3log10 IU/ml vs. 2.6±1.0log10 IU/ml at week 104, P=0.001). At week 104 the rates of HBV DNA undetectable and HBeAg loss in group 2 were significantly higher than those in group 1 (P<0.05). Along with the increased nucleotide change rates, the rate of HBV DNA undetectable at week 104 tended to increase (odds ratio=0.323, 95% confidence interval=0.138-0.758, P<0.001).
CONCLUSION: Our findings suggested that the nucleotide changes within HBV CP/preC region during the first 12-week treatment might be associated with a better virological response.