Variability of the preC/C region of hepatitis B virus genotype A from a South African cohort predominantly infected with HIV

Mayaphi, Simnikiwe H.; Martin, Des; Mphahlele, M. Jeffrey; Blackard, Jason T.; Bowyer, Sheila Mary

doi:10.1002/jmv.23695

Cited by 12 publications

(10 citation statements)

References 36 publications

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“…The HBV genotype D is second to genotype A in terms of predominance in Southern Africa, with the dominant D subgenotype reported to be the D3 [20,29]. However, a recent South African study isolated the subgenotype D4 [26] as was the case in the current study, showing potential importation from other countries like Kenya [24] and Somalia [29] where the D4 subgenotype has been reported.…”

Section: Discussionmentioning

confidence: 51%

Hepatitis B virus infection in post-vaccination South Africa: Occult HBV infection and circulating surface gene variants

Amponsah-Dacosta

Lebelo

Rakgole

et al. 2015

Journal of Clinical Virology

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Background and objective The aim of this study was to investigate the prevalence of occult hepatitis B virus (HBV) infection and the HBV surface (S) gene variants circulating in the South African population after nearly two decades of universal hepatitis B vaccination. Study design From a previous serosurvey, 201 serum samples with serological evidence of exposure to HBV were identified and these were stratified into post- and pre-vaccine introduction populations. For all samples, HBV DNA was screened and quantified using a real-time PCR assay and results analysed together with HBV serological markers. Where HIV results were available, subset analysis was performed. The HBV S gene was PCR-amplified and sequences analysed for a total of 37 isolates. Results The prevalence of occult HBV infection reduced from 70.4% in the pre-vaccine introduction era to 66.0% post-vaccine introduction. There was an association between HIV infection and an increase in prevalence of occult HBV infection within the post-vaccine introduction population, although this was not statistically significant. Furthermore, sequence analysis revealed the following HBV subgenotypes; A1 (n = 34), A2 (n = 2) and a rare D4 isolate. HBV S gene variants, including diagnostic escape mutants were isolated. Conclusion There was a decline in the prevalence of occult HBV infection in post-vaccination South Africa, although the disease burden remains significant in the HIV co-infected population. After nearly two decades of a universal hepatitis B vaccination programme, no positive selection of vaccine escape mutants were observed.

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Section: Discussionmentioning

confidence: 51%

Hepatitis B virus infection in post-vaccination South Africa: Occult HBV infection and circulating surface gene variants

Amponsah-Dacosta

Lebelo

Rakgole

et al. 2015

Journal of Clinical Virology

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“…HBV preC/C primers were used for nested HBV‐PCR as previously described . Sequencing was performed at Inqaba Biotechnical company using published preC/C primers and method …”

Section: Methodsmentioning

confidence: 99%

Nosocomial outbreak of hepatitis B virus infection in a pediatric hematology and oncology unit in South Africa: Epidemiological investigation and measures to prevent further transmission

Büchner

Plessis

Reynders³

et al. 2015

Pediatric Blood & Cancer

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Background Hospital‐acquired hepatitis B virus (HBV) infection has been well described and continues to occur worldwide. Recent nosocomial outbreaks have been linked to unsafe injection practices, use of multi‐dose vials, and poor staff compliance with standard precautions. This report describes a nosocomial outbreak that occurred in a pediatric hematology and oncology unit of a large academic hospital, the epidemiological investigation of the outbreak, and preventive measures implemented to limit further in‐hospital transmission. Methods Outbreak investigation including contact tracing and HBV screening were initially carried out on all patients seen by the unit during the same period as the first three cases. Routine screening for the entire patient population of the unit was initiated in February 2013 when it was realized that numerous patients may have been exposed. Results Forty‐nine cases of HBV infection were confirmed in 408 patients tested between July 2011 and October 2013. Phylogenetic analysis of the HBV preC/C gene nucleotide sequences revealed that all tested outbreak strains clustered together. Most (67%) patients were HBeAg positive. The cause of transmission could not be established. Preventive measures targeted three proposed routes. HBV screening and vaccination protocols were started in the unit. Conclusions The high number of HBeAg positive patients, together with suspected lapses in infection prevention and control measures, are believed to have played a major role in the transmission. Measures implemented to prevent further in‐hospital transmission were successful. On‐going HBV screening and vaccination programs in pediatric hematology and oncology units should become standard of care. Pediatr Blood Cancer © 2015 Wiley Periodicals, Inc.

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“…Within the continent, data on the prevalence of pc mutations in both HBV mono‐infected and HIV‐HBV co‐infected patients are certainly available . However, their implications with respect to virological and serological response during anti‐HBV NA therapy remain to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

“…11 The pcG1896A mutation would then appear to impose serious consequences on the therapeutic course of NA-treated patients.Within the continent, data on the prevalence of pc mutations in both HBV mono-infected and HIV-HBV co-infected patients are certainly available. [12][13][14][15][16] However, their implications with respect to virological and serological response during anti-HBV NA therapy remain to be elucidated. In the study herein, we used unique data from a cohort of antiretroviral treatment (ART)-naïve HIV-HBV co-infected patients from Côte d'Ivoire initiating treatment with an anti-HBV containing regimen.…”

mentioning

confidence: 99%

Precore G1896A mutation is associated with reduced rates of HBsAg seroclearance in treated HIV hepatitis B virus co‐infected patients from Western Africa

Boyd

Moh

Maylin

et al. 2018

Journal of Viral Hepatitis

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The nucleotide substitution G1896A on the precore (pc) region has been implicated in virological and serological responses during treatment in hepatitis B virus (HBV)-infected patients. Whether this mutation affects the therapeutic course of HIV-HBV co-infected patients, especially from Western Africa, is unknown. In this prospective cohort study, 86 antiretroviral (ARV)-naïve HIV-HBV co-infected patients from Côte d'Ivoire, initiating ARV-treatment containing lamivudine (n = 53) or tenofovir (n = 33), had available baseline pc sequences. Association of the pcG1896A mutation with time to undetectable HBV-DNA, hepatitis B "e" antigen (HBeAg) seroclearance (in HBeAg-positive patients), and hepatitis B surface antigen (HBsAg) seroclearance was evaluated using Cox proportional hazards regression. At ARV-initiation, median HBV-DNA was 6.04 log copies/mL (IQR = 3.70-7.93) with 97.7% harbouring HBV genotype E. Baseline pcG1896A mutation was identified in 51 (59.3%) patients, who were more commonly HBeAg-negative (P < .001) and had basal core promotor A1762T/G1764A mutations (P < .001). Patients were followed for a median 36 months (IQR = 24-36). Cumulative proportion of undetectable HBV-DNA was significantly higher in patients with baseline mutation (pcG1896A = 86.6% vs no pcG1896A = 66.9%, P = .04), but not after adjusting for baseline HBV-DNA levels and anti-HBV agent (P = .2). No difference in cumulative proportion of HBeAg seroclearance was observed between mutation groups (pcG1896A = 57.1% vs no pcG1896A = 54.3%, P = .7). Significantly higher cumulative proportion of HBsAg seroclearance was observed in patients without this mutation (pcG1896A = 0% vs no pcG1896A = 36.9%, P < .001), even after adjusting for baseline HBsAg quantification and anti-HBV agent (P < .001). In conclusion, lacking the pcG1896A mutation before ARV initiation appeared to increase HBsAg seroclearance rates during treatment. The therapeutic implications of this mutation need further exploration in this setting.

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Variability of the preC/C region of hepatitis B virus genotype A from a South African cohort predominantly infected with HIV

Cited by 12 publications

References 36 publications

Hepatitis B virus infection in post-vaccination South Africa: Occult HBV infection and circulating surface gene variants

Hepatitis B virus infection in post-vaccination South Africa: Occult HBV infection and circulating surface gene variants

Nosocomial outbreak of hepatitis B virus infection in a pediatric hematology and oncology unit in South Africa: Epidemiological investigation and measures to prevent further transmission

Precore G1896A mutation is associated with reduced rates of HBsAg seroclearance in treated HIV hepatitis B virus co‐infected patients from Western Africa

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