Characterization of hepatitis B virus mutations in untreated patients co-infected with HIV and HBV based on complete genome sequencing
ABSTRACT Co-infection of HBV with HIV results in an accelerated course of HBV-associated chronic liver disease. Several studies have shown that viral mutations are related to disease progression in mono-infection with HBV. However, it is unclear whether HBV mutation patterns might differ between co-infected and mono-infected patients. To compare the frequencies and mutation patterns in the HBV genome between co-infection and mono-infection. Twenty-four treatment-naïve co-infected and 31 treatment-naïve mono-infected Thai patients were included. HBV mutations were characterized by whole genome sequencing of virus serum samples. The clinical features and frequency of known clinically significant mutations were compared between the two groups. No significant difference between the groups was found with respect to sex, age and HBeAg. However, HBV DNA levels were significantly higher in co-infected patients. The distribution of HBV genotypes was comparable between the two groups and restricted mostly to sub-genotypes C1 and B2. An isolate with recombinants of genotypes G/C1 was also identified in a patient with co-infection. There was no difference in the prevalence of mutations in the enhancer II/basal core promoter/precore region, pre-S/S and polymerase genes between the two groups. In conclusion, dual infections tend to engender increased HBV DNA levels. There was no major difference in the frequencies of common HBV mutations between co-infected and mono-infected patients. Thus, HBV mutations may not contribute to disease pathogenesis in Thai patients with co-infection. J. Med. Virol. © 2012 Wiley Periodicals, Inc.
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ABSTRACT: Hepatitis B virus (HBV) infection is endemic in South Africa however, there is limited data on the degree of liver disease and geographic variation in HIV/HBV coinfected individuals. In this study, we analysed data from the CIPRA-SA 'Safeguard the household study' in order to assess baseline HBV characteristics in HIV/HBV co-infection participants prior to antiretroviral therapy (ART) initiation. 812 participants from two South African townships Soweto and Masiphumelele were enrolled in a randomized trial of ART (CIPRA-SA). Participants were tested for hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and HBV DNA. FIB-4 scores were calculated at baseline. Forty-eight (5.9%) were HBsAg positive, of whom 28 (58.3%) were HBeAg positive. Of those with HBV, 29.8% had an HBV DNA<2000 IU/ml and ALT<40 IU/ml ; 83.0% had a FIB-4 score <1.45, consistent with absent or minimal liver disease. HBV prevalence was 8.5% in Masiphumelele compared to 3.8% in Soweto (relative risk 2.3; 95% CI: 1.3-4.0). More participants in Masiphumelele had HBeAg-negative disease (58% vs. 12%, p = 0.002) and HBV DNA levels ≤2000 IU/ml, (43% vs. 6% p<0.007). One third of HIV/HBV co-infected subjects had low HBV DNA levels and ALT while the majority had indicators of only mild liver disease. There were substantial regional differences in HBsAg and HbeAg prevalence in HIV/HBV co-infection between two regions in South Africa. This study highlights the absence of severe liver disease and the marked regional differences in HIV/HBV co-infection in South Africa and will inform treatment decisions in these populations.PLoS ONE 12/2013; 8(12):e74900. DOI:10.1371/journal.pone.0074900 · 3.53 Impact Factor
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ABSTRACT: The number of cases of HBV infection reported by the WHO for each district and country is positively correlated with the number of HBV sequences in the database isolated from the corresponding district and country. This study determined distribution characteristics of HBV genotypes and subtypes in 14 countries neighboring China. The progress made in genomic research involving HBV was also reviewed. Nine hundred fifty-one complete genome sequences of HBV from 14 countries neighboring China were selected from NCBI. The sequence-related information was analyzed and recorded. One hundred seventy-two sequences of HBV genotype B were screened for alignment using DNA star and MEGA 5.1. Dominant HBV genotypes in the countries neighboring China were genotypes B, C and D and dominant subtypes were adw2 and adrq+. The association between genotype and serotype of HBV in these countries was shown to differ from previous research results. As shown by sequence alignment, the sequence divergence between five subgenotypes (B3, B5, B7, B8 and B9) was below 4%. The B subgenotypes shared six common specific amino acid sites in the S region. The B3, B5, B7, B8 and B9 subgenotypes can be clustered into quasi-sub-genotype B3 and the open reading frame of HBV has a start codon preference; however, whether a mutation in the start codon in the pre-S2 region has an impact on survival and replication of HBV remains to be determined.Hepatitis Monthly 05/2015; 15(5). DOI:10.5812/hepatmon.15(5)2015.24422 · 1.80 Impact Factor