The association of HBV core promoter double mutations (A1762T and G1764A) with viral load differs between HBeAg positive and anti-HBe positive individuals: A longitudinal analysis
Authors: XiaoPing Pan, Haijun Huang, WeiBo Du, LanJuan Li
Journal: Journal of Hepatology (2009)

We read with great interest the study by Fang and colleagues [[1]Fang Z.L. Sabin C.A. Dong B.Q. Wei S.C. Chen Q.Y. Fang K.X. et al.The association of HBV core promoter double mutations (A1762T and G1764A) with viral load differs between HBeAg positive and anti-HBe positive individuals: a longitudinal analysis.J Hepatol. 2009; 50: 273-280Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar] that evaluated the association of HBV core promoter double mutations (A1762T and G1764A) with viral loads between HBeAg positive and anti-HBe positive individuals. In their study, the authors concluded that BCP double mutations are associated with lower viral loads in HBeAg positive individuals, but have no effect on the viral loads of anti-HBe positive individuals. Our concerns regarding this study and its conclusions are outlined as follows: It is well known that treatment with an antiviral therapy, such as lamivudine therapy, can give rise to HBV mutations, including core promoter mutations [[2]Chen C.H. Lee C.M. Lu S.N. Changchien C.S. Wang J.C. Wang J.H. et al.Comparison of sequence changes of precore and core promoter regions in HBeAg-positive chronic hepatitis B patients with and without HBeAg clearance in lamivudine therapy.J Hepatol. 2006; 44: 76-82Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar] or biochemical and virological breakthrough [[3]Yuen M.F. Sablon E. Hui C.K. Yuan H.J. Decraemer H. Lai C.L. Factors associated with hepatitis B virus DNA breakthrough in patients receiving prolonged lamivudine therapy.Hepatology. 2001; 34: 785-791Crossref PubMed Scopus (357) Google Scholar]. Moreover, antiviral therapies, including nucleotide analogy, are widely used for the treatment of hepatitis B in urban and rural areas of China. Although the authors have mentioned that no subject received antiviral or immunosuppressive therapy during the 3-year follow-up period, the authors still have not stated whether the subjects enrolled in the present study had been treated with any antiviral therapy in the early days prior to their inclusion in the study. In other words, if some subjects enrolled in this study had received antiviral therapy prior to the study, which could have influenced the results. Therefore, it is important to further address the above-mentioned question in the context of the study. The effect of BCP double mutations on viral loads remains uncertain [1Fang Z.L. Sabin C.A. Dong B.Q. Wei S.C. Chen Q.Y. Fang K.X. et al.The association of HBV core promoter double mutations (A1762T and G1764A) with viral load differs between HBeAg positive and anti-HBe positive individuals: a longitudinal analysis.J Hepatol. 2009; 50: 273-280Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar, 4Buckwold V.E. Xu Z. Chen M. Yen T.S. Ou J.H. Effects of a naturally occurring mutation in the hepatitis B virus basal core promoter on precore gene expression and viral replication.J Virol. 1996; 70: 5845-5851Crossref PubMed Google Scholar, 5Chen W.N. Oon C.J. Mutations and deletions in core promoter and precore stop codon in relation to viral replication and liver damage in Singaporean hepatitis B virus carriers.Eur J Clin Invest. 2000; 30: 787-792Crossref PubMed Scopus (23) Google Scholar]. In this study, cross-sectional analysis and longitudinal analysis have been utilized for evaluating the association of HBV core promoter double mutations (A1762T and G1764A) with viral loads, and more reliable results have been obtained by the authors [[1]Fang Z.L. Sabin C.A. Dong B.Q. Wei S.C. Chen Q.Y. Fang K.X. et al.The association of HBV core promoter double mutations (A1762T and G1764A) with viral load differs between HBeAg positive and anti-HBe positive individuals: a longitudinal analysis.J Hepatol. 2009; 50: 273-280Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar]. However, viral replication, as measured by viral loads in vivo, is influenced by the interaction of the virus with the host immune system, and this has been admitted by the authors and colleagues [[1]Fang Z.L. Sabin C.A. Dong B.Q. Wei S.C. Chen Q.Y. Fang K.X. et al.The association of HBV core promoter double mutations (A1762T and G1764A) with viral load differs between HBeAg positive and anti-HBe positive individuals: a longitudinal analysis.J Hepatol. 2009; 50: 273-280Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar] and ascertained by Chu and colleagues [[6]Chu C.J. Hussain M. Lok A.S. Quantitative serum HBV DNA levels during different stages of chronic hepatitis B infection.Hepatology. 2002; 36: 1408-1415Crossref PubMed Scopus (268) Google Scholar]. That is to say, when we are attempting to investigate viral loads, we should also be paying attention to the influence of the viral and host factors, such as age, sex and viral genotype, etc., on viral loads. In Table 3 [[1]Fang Z.L. Sabin C.A. Dong B.Q. Wei S.C. Chen Q.Y. Fang K.X. et al.The association of HBV core promoter double mutations (A1762T and G1764A) with viral load differs between HBeAg positive and anti-HBe positive individuals: a longitudinal analysis.J Hepatol. 2009; 50: 273-280Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar], however, the authors have not provided any details regarding the baseline characteristics of subjects, including age, sex and viral genotype, either for the BCP double mutation subgroup or for the wild-type subgroup. Moreover, it is also unclear whether viral loads were associated with the other factors considered, including age, sex and viral genotype, either in the BCP double mutations subgroup or in the wild-type subgroup. Therefore, the aforementioned question needs to be considered and further investigated.