Browsing by Author "Chotun, Bibi Nafiisah"
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- ItemHepatitis b virus-related hepatocellular carcinoma in south africa: investigations into the risk profile of a previously unscreened population from the Western Cape(Stellenbosch : Stellenbosch University, 2018-12) Chotun, Bibi Nafiisah; Anderson, Monique Ingrid; Preiser, Wolfgang; Fernandez, Pedro; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Pathology. Medical Virology.ENGLISH ABSTRACT: Hepatocellular carcinoma (HCC) is a neglected major public health problem worldwide. In SubSaharan Africa (SSA), most HCC cases are diagnosed with advanced disease, well past the timing of possible treatment. Most HCC cases worldwide are caused by chronic infection with hepatitis B virus (HBV). Although the bulk of the burden of HBV is in SSA, there are no screening programmes implemented in the general African population so only 0.8% of HBV-infected individuals are diagnosed. Most research on HBV-related HCC has been conducted in Asia, where HBV is also endemic, but where there are differences in disease progression and presentation. The present study investigated HBV and HCC from an African perspective and tackled these public health issues by incorporating three key components for early diagnosis of HBV-related HCC: HBV screening, HCC biomarkers, and HBV-related HCC genomics. The HBV screening study found the prevalence of HBV in a South African community-based cohort using a validated point-of-care test to be 2.2% (95% CI: 1.4%–3.3%). The test performed well in the field and had a sensitivity, specificity, negative and positive predictive values of 100%. The test was also accepted by the community (93% uptake) and health care providers. The results of the present study support the case for the implementation of HBV screening in South Africa by demonstrating the magnitude of the HBV health problem in South Africa and new evidence that the POCT test performs well in the field, is accepted by the community and health care providers, and that patients diagnosed with the test can be successfully linked to treatment and long-term follow-up. The HCC biomarker study found significant differences in methylation expression levels in CpG islands in the promoter region of the tumour suppressor gene RASSF1A between HCC cases and normal liver tissue controls as well as a significant association between HBV genotype A and HCC. Although the sample size was small, it showed that there are biomarkers that may be used to identify HCC, paving the way for future studies looking into developing HCC risk scores for early diagnosis of HCC. Using whole-exome sequencing, the HBV-related HCC genomics study identified two novel germline variants in the SMARCA1 and RAB19 genes that in the absence of other risk factors besides HBV infection, could have contributed to early-onset HBV-related HCC in their respective hosts. Overall, these data provide evidence that early diagnosis of HBV-related HCC in an African setting is possible especially if a multi-targeted approach is taken. The simplest approach to minimise the incidence of HCC in SSA would be to implement HBV screening, at the very least in pregnant women, to break the transmission cycle of HBV. Moreover, the biomarkers of interest identified in the present study should be investigated further in larger cohorts and non-invasive patient samples to determine their utility in stratifying HCC risk. Lastly, the WES study showed that there are germline variants that could predispose carriers to HCC although these results need to be further investigated in in-silico and proteomic studies.
- ItemThe prevalence of Hepatitis B virus infection in an HIV-exposed paediatric cohort from the Western Cape, South Africa(Stellenbosch : Stellenbosch University, 2012-12) Chotun, Bibi Nafiisah; Andersson, Monique I.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Pathology Medical Virology..ENGLISH ABSTRACT: Despite the availability of Hepatitis B virus (HBV) vaccination for over three decades, this infection remains a major public health problem. Whilst the WHO recommends giving a birth dose of the vaccine, in South Africa, routine infant HBV vaccination commences at six weeks of age. This schedule is based on data from the pre-HIV era which showed transmission occurred via the horizontal, rather than the vertical route. In the era of HIV however, maternal HIV co-infection may release HBV from immune control, resulting in higher HBV loads and increasing the risk of vertical transmission. The aim of this study was to determine the prevalence and character of HBV infection in HIV-exposed infected and uninfected infants. Residual plasma samples from routine HIV nucleic acid testing of 1000 HIV-exposed infants aged between 0 and 18 months from the Western Cape were tested. Samples were tested for HBsAg by ELISA (Murex HBsAg Version 3) and confirmed by neutralisation. HBV DNA was quantified using an in-house real-time PCR assay. Infants with HBsAg positive samples were followed up and a blood sample was collected from mother and child. Those HBsAg positive samples were tested for HBeAg/antiHBe (Diasorin) and HBsAg negative samples were tested for antiHBs. HBV DNA was quantified. The surface gene was sequenced and the HBV genotype determined by phylogenetic analysis using HepSEQ (www.hepseq.org.uk). Whole genome sequencing was also performed. Of 1000 samples tested, four samples were positive for HBsAg and/or HBV DNA, indicating a prevalence of HBV transmission of 0.4%. At follow-up, two of three infected infants were positive for HBsAg, with HBV viral loads of greater than 108 IU/ml. The third infant was found to have cleared his infection and the fourth child was lost to follow up. These infected infants had all received HBV vaccination. All four mothers were HBeAg positive. Sequencing analysis showed the HBV strains from the two infants and four mothers belonged to subgenotype A1. The two mother-child paired sequences were identical. The data from this study shows that vertical transmission of HBV infection in HIV-exposed infants from the Western Cape is occurring, despite vaccination. Data from the Western Cape, showing an HBV prevalence of 3.4% in HIV-infected pregnant women, and those presented here suggest a vertical transmission rate of HBV of 12%. This is despite the widespread use of tenofovir and lamivudine in HIV-infected women with low CD4 counts. This study provides data supporting calls to bring HBV vaccination closer to the time of birth. Further work is urgently needed to confirm these findings and to determine the rates of transmission in HIV-unexposed infants.