| Objectives:To determine whether the nucleotide sequence of hepatitis B virus (HBV), and HBeAg, influence the correlation between serum HBsAg levels and viral loads, with the aim of clarifying whether the serum HBsAg titer may be used as a surrogate marker of serum HBV DNA in chronic HBV infection.Methods:The study subjects were recruited from the Long An cohort. Their serum samples for analysis were drawn during the first to third rounds of follow-up. Serum HBsAg titers were measured by a commercial chemiluminescent microparticle immunoassay. Serum HBV DNA concentrations were quantified by real time PCR. The HBV preS/S, PreC and basal core promoter regions were amplified using nested PCR. HBV DNA positive products were sequenced using a BigDye Terminator V3.1 Cycle Sequencing kit. The data were analysed using SPSS software (ver.16.0). Continuous and categorical variables were compared between the groups using, respectively, the Mann-Whitney test and the chi-square/Fisher’s exact test. Pearson’s correlation coefficient (r) was used to describe the correlation between two continuous, normally distributed variables. Spearman’s correlation was used where the variables were not distributed normally. Simple and multiple linear regression analyses were performed to identify independent factors for serum HBsAg titer quantification.Results:Eighty-nine study subjects were recruited from the Long An cohort,52 males and 37 females. Their mean age was 37.5±6.2 years. Twenty four study subjects were HBeAg-positive and 65 were HBeAg-negative. The distribution of serum HBsAg titer across the study subjects is skewed. The median (range) of HBsAg is 2.9×103 IU/ml (5.0×101-4.6×105). The median (range) of viral loads is 3.0×105 IU/ml (5×102-4.8×108).1) Viral loads of mutant HBV are lower than those of wild type HBV (P<0.05).2) In the first round of follow up, the serum HBsAg titer was positively correlated with serum HBV DNA in both HBeAg positive and negative subjects (r=0.449, P= 0.013;r=0.300, P=0.018, respectively). The correlation could also be seen in the third round samples (r=0.782, P<0.001)for the HBeAg positive group; r=0.279, P=0.028) for the HBeAg negative group. In the second round samples, although the correlation was seen only in the HBeAg positive group, the P value of the HBeAg negative group is close to significance (r=0.229, P=0.078).3) Chronic HBV infection has a complicated course and four phases have been identified:immune tolerant, immune clearance, inactive and immune escape phase. No correlation between serum HBsAg titer and HBV DNA concentrations was found for any of the phases (n=19, r=0.423, P=0.071; n=5, r=0.838, P=0.077; n=45, r=0.242, P=0.110 and n=17, r=0.421, P=0.092, respectively).4) The serum HBsAg titers were positively correlated with serum HBV DNA concentrations in the first round samples from the groups with wild type sequences of the preS/S, BCP and PreC regions (r=0.502, P=0.040). However, the correlation was not seen in the same round samples from the groups with mutant sequences (r=0.165, P=0.257). These findings are supported by the results from the second and third rounds of follow up (r=0.553, P=0.026,r =0.671, P=0.004 for the wild type group; r=0.148, P=320;r=0.220, P=0.125 for the mutant group)5) The multiple linear regression analysis revealed that HBV DNA concentrations and HBeAg status affect significantly the levels of serum HBsAg.Conclusions:The presence or absence of HBeAg does not influence the correlation between serum HBsAg titer and HBV DNA concentrations, while the sequence of HBV DNA does influence the correlation. The serum HBsAg titers were positively correlated with serum HBV DNA concentrations in individuals infected with wild type HBV, while the correlation was not seen in those infected with mutant virus, suggesting that the serum HBsAg titer may be used as a surrogate marker of serum HBV DNA only in those infected with wild type HBV. |
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