Pajaree Treesuwan. Genetic diversity of hepatitis B virus in pregnant women with human immunodeficiency virus and hepatitis B virus co-infection. Master's Degree(Medical Technology). Chiang Mai University Library. : Chiang Mai University, 2016.
Genetic diversity of hepatitis B virus in pregnant women with human immunodeficiency virus and hepatitis B virus co-infection
Abstract:
Background & Aims: Despite effective vaccines against HBV are available in Asia Pacific, perinatal HBV transmission still continues to occur. High maternal HBV viral load is a major risk factor for perinatal transmission of HBV however impact of HBV genetic diversity on perinatal transmission is unclear. Since HIV infection increases HBV replication analysis of HBV genetic diversity among HBV/HIV co-infected pregnant women may help to assess its impact on perinatal transmission of HBV. This study aimed to assess the relationship between 1) HBV genetic diversity and perinatal HBV transmission and 2) HBV genetic diversity and HBeAg negativity in HBV/HIV co-infected pregnant women.
Methods: This is a retrospective analysis study using samples and data collected from two large perinatal HIV prevention trials conducted in Thailand during 1997-1999 (PHPT-1 and PHPT-2). HBV/HIV co-infected women with HBV DNA levels ≥3.5 log10 IU/mL were included in this study. To assess the relationship between HBV genetic diversity and perinatal HBV transmission, 9 HBV transmitting mothers were matched to HBV non-transmitting mothers on a ratio of 1:2 according to their baseline HBV DNA levels and HBeAg status. To assess the relationship between HBV genetic diversity andabsence of HBeAg in plasma, 15 women HBeAg negative and 15 women HBeAg positive were randomly selected. Full-length HBV genome was directly sequenced using BigDye Terminator V. 3.1 cycle sequencing kit. HBV genotypes were identified using phylogenetic analysis and web-based tools. HBV genetic diversity was analyzed and compared between groups using 1) Shannon entropy scores, 2) mean genetic distance 3) dN/dS ratio and 4) mutation patterns.
Results: Of 49 pregnant women with available HBV sequence, 44 women were infected with HBV genotype C, 4 with genotype B and one was infected with an inter-genotype recombinant C/G. HBV transmitting women had higher genetic diversity in preS/S regions, using Shannon entropy, than non-transmitting women (0.067vs 0.043; p<0.0001) but this difference disappeared when only HBV genotype C viruses were considered. This study observed several well-known and potential mutations, precore A1896G mutation and basal core promoter (BCP) T1762/A1764 mutations, across the whole HBV genome but no particular mutation pattern was associated with perinatal transmission. HBeAg-negative women had higher genetic diversity than HBeAg positive women (0.063 vs. 0.045; p <0.0001) but this difference disappeared when only HBV genotype C viruses were considered.
Conclusions: Assessment of viral factors associated with perinatal transmission of HBV may provide information useful for the design of new and highly effective vaccine to better prevent HBV infection. However, in our study, perinatal transmission of HBV was not associated with a higher genetic diversity of HBV or particular mutation pattern. Higher HBV genetic diversity in women who seroconverted HBeAg may be due more rapid evolutionary rates of HBeAg negative sequences. In addition, large-scale studies are needed to evaluate the prevalence of A1896G mutation and its impact on the result of HBeAg testing and thus, the usefulness of HBeAg testing. Were this prevalence high, HBV DNA quantification would be the appropriate approach to assess viral replication in all HBeAg negative people.