95 research outputs found
An investigation of hepatitis B virus in antenatal women tested for human immunodeficiency virus, in the Western Cape Province of South Africa
No full textThesis (MScMedSc)--Stellenbosch University, 2012.ENGLISH ABSTRACT: Hepatitis B virus (HBV) immunisation protocols in much of Africa are based on data from the pre-human immunodeficiency virus (pre-HIV) era that indicated that HBV transmission occurs predominantly horizontally between siblings and play-mates rather than vertically from mother to child. The immunosuppression associated with HIV infection however may release HBV from immune control resulting in higher HBV viral loads, which may increase the risk of perinatal mother to child transmission of HBV. The aim of this study was to determine the prevalence and characteristics of chronic HBV infection in HIV-infected pregnant women compared to HIV-uninfected pregnant women in the Western Cape province of South Africa.
Ethical approval was obtained to conduct a retrospective, matched case-control, unlinked anonymous study using residual plasma samples from the 9355 pregnant women included in the Western Cape's 2008 National HIV and Syphilis Antenatal Survey. Samples were tested for HBsAg on the AxSYM (Abbott, Chicago, IL) and confirmed by neutralization. Confirmed HBsAg-positive samples were tested for HBeAg, anti-HBe and anti-HD (Diasorin, Saluggia, Italy) and had HBV viral load and genotyping done. In addition, HBsAg-negative samples were tested for anti-HBc.
Samples from 1549 HIV-infected pregnant women were included and matched to the same number of samples from age- and race-matched HIV-uninfected women. Median age of 26 years, parity and education were similar in the two groups. The prevalence of HBsAg was 3.4% for the HIV-infected group and 2.9% for the HIV-uninfected group. HBV DNA loads of greater than 104 IU/ml were detected in 32.1% of HBsAg-positive, HIV/HBV co-infected women, and in 14.3% HBsAg positive, HBV mono-infected women. Among the HIV-infected group 18.9% of HBsAg-positive were HBeAg positive, with a median viral load of 7.93 log10 IU/ml; whilst 15.5% HIV-uninfected women were positive for HBeAg with a median viral load of 6.07 log10 IU/ml. Genotype A was seen in 92.6% of the isolates while 7.4% of the isolates were genotype D. Serum total anti-HBc antibodies that are a marker of past infection were detected in 42.2% of HIV-infected and in 24.1% of HIV-uninfected women that were negative for HBsAg. No positive sample for anti-HD was seen among all HBsAg-positive samples. This data indicates that there is increased exposure to HBV in HIV-infected pregnant women than in HIV-uninfected women and that a greater proportion of HIV-infected pregnant women compared to HBV mono-infected pregnant women may be at increased risk of transmitting HBV to their infants. Further studies are needed to determine the rate of vertical transmission of HBV in the HIV era.AFRIKAANSE OPSOMMING: Hepatitis B virus (HBV) immunisasie protokolle vir meeste dele van Afrika is gebaseer op data versamel in die era voor MIV. Die data dui aan dat HBV oordrag hoofsaaklik deur horisontale transmissie tussen broers, susters en speelmaats eerder as vertikale transmissie van moeder na kind plaasvind. Die onderdrukking van die immuunstelsel as gevolg van MIV infeksie kan egter lei tot 'n verhoogde risiko van perinatale HBV oordrag van moeder na kind. Die doel van hierdie studie was om die voorkoms en karakter van chroniese HBV infeksie in MIV-positiewe swanger vroue te vergelyk met die van MIV-negatiewe swanger vroue.
Etiese goedkeuring is verkry om 'n retrospektiewe, deursnee-, ongekoppelde anonieme studie uit te voer wat gebruik maak van oorblywende plasma monsters van 9355 swanger vroue wat ingesluit is in die Wes-Kaap 2008 Nasionale MIV en Sifilis Voorgeboortelike Opname. Die monsters was getoets vir HBsAg antiliggame (AxSYM, Abbott, Chicago, IL) en bevestig deur neutralisasie toetse. Positiewe monsters was getoets vir HBeAg en anti-HBe (Diasorin, Saluggia, Italië). HBV viruslading en genotipering was ook op HBsAg positiewe monsters gedoen. Die HBsAg negatiewe monsters was getoets vir die teenwoordigheid van anti-HBc.
Monsters van 1549 MIV-positiewe swanger vroue was ingesluit in die studie. Dieselfde aantal monsters van MIV-negatiewe vroue, met ooreenstemende ouderdom en etnisiteit, was ingesluit as kontroles. Die gemiddelde ouderdom van albei groepe was 26 jaar. Pariteit en opvoeding was dieselfde in albei groepe. Die voorkomssyfer van HbsAg was 3.4% in die MIV-positiewe groep en 2.8% in die MIV-negatiewe groep. HBV DNS ladings van meer as 104 IU/ml was waargeneem in 32.1% van die MIV-mede-geinfekteerde vroue en in 14.3% van die MIV-negatiewe groep. In die MIV-positiewe groep was 18.9% vroue HBeAg positief, met 'n gemiddelde virale lading van 7.93 log10 IU/ml, terwyl 15.5% MIV-negatiewe vroue positief was vir HBeAg met 'n gemiddelde virale lading van 6.07 log10 IU/ml. In ons studie was 92.6% van die monsters genotipe A en 7.4% genotipe D. Toatale anti-HBc antiliggame, 'n merker van vorige infeksie, was gevind in 42.2% van MIV-mede-geïnfekteerde vroue en 24.1% van MIV-negatiewe vroue wat negatief was vir HBsAg antiliggame.
Data van ons studie dui op 'n verhoogde risiko vir vertikale HBV transmissie van MIV-positiewe moeders na hul babas. Verdere studies word benodig om vas te stel of vertikale transmissie van HBV van MIV-positiewe vroue na hul babas plaasvind.Wellcome TrustPoliomyelitis Research Foundatio
Hepatitis B virus-associated hepatocellular carcinoma in South Africa: epidemiology and impact of HIV-1 co-infection and immune dysregulation
No full textThesis (PhD)--Stellenbosch University, 2016ENGLISH ABSTRACT : Co-infection with the human immunodeficiency virus (HIV) negatively impacts the natural progression of hepatitis B virus (HBV) infection, including causing rapid progression to liver fibrosis and hepatocellular carcinoma (HCC). In sub-Saharan Africa the overlap between high HIV and HBV prevalence may increase the incidence of HCC. The aim of this study was to investigate the effect of HIV co-infection on presentation of HCC among HBV-infected patients. Since HCC is thought to be driven by ongoing severe inflammation, the study also evaluated the association between the expression of markers of immune activation/exhaustion and liver inflammation in patients with chronic hepatitis B (CHB) to determine if the risk of hepatofibrosis is increased by exposure to gut microbial products and compared HIV-infected patients with HBV-infected and HIV-HBV co-infected patients.
Ethical approval was obtained to conduct two sub-studies. The first sub-study (HCC Epidemiology Study) involved recruitment of patients diagnosed with HCC at oncology units of selected teaching hospitals in South Africa. A total of 107 HCC cases were recruited between December 2012 and October 2015. Demographic, laboratory and clinical data together with blood specimens were collected. Patients were tested for HBV, hepatitis C virus (HCV) and HIV. Molecular characterization of HBV and HCV was also performed. For the second sub-study (Liver Fibrosis and Immune Markers Study), 46 HBV/HIV co-infected; 47 HBV monoinfected; 39 HIV monoinfected and; 39 HIV-/HBV-uninfected controls were recruited following informed consent. All HIV-infected patients had been on highly active antiretroviral therapy (HAART) for ≥3 months. Liver stiffness measurements were taken using the Fibroscan 402. Cell-based immunomarkers of activation/exhaustion were measured using flow cytometry of fresh whole blood. Soluble serum/plasma immunomarkers were measured using ELISA and Luminex. HIV and HBV viral loads and genotyping of HBV were performed.
Of 107 cases in the HCC Epidemiology study, 83 (78%) were male and 68/106 (64%, 95% CI: 59-77) were positive for HBsAg. HIV seropositivity was seen in 22/100 (22%, 95% CI: 14-30) of all HCC cases. Among HBsAg-positive HCC cases, 19/66 (29%, 95% CI: 18-40) were HIV-infected compared to only 3/34 (9%) among those that were HBsAg-negative, p=0.04. The proportion of females among the HBV/HIV co-infected HCC cases 6/18 (33%, 95% CI: 11-55) was significantly higher compared to those that were HBV-mono-infected 6/47 (13%, 95% CI: 3-23), p=0.005. HIV/HBV co-infected females presented younger, at mean age 36.8 years (95% CI: 32.2-41.5) compared to 50.5 years (95% CI: 30.2-70.8) in HBV-mono-infected women, p=0.09. Males continue to be disproportionally affected with HCC. There is a trend towards younger age at diagnosis of HCC among HIV-positive compared to HIV-negative women.
The Liver Fibrosis and Immune Markers Study showed a high percentage of CD8+ T lymphocytes from co-infected subjects expressing HLA-DR/CD38 and PD-1 (p<0.05). Soluble CD14 and IP-10 were also significantly elevated in plasma of co-infected patients. Co-infected subjects exhibited delayed immune recovery with lower CD4/CD8 T cell ratio; CD4 cell counts and frequent HIV viremia compared to HIV mono-infected participants (p<0.05). The HBV mono-infected group had the highest proportion of participants with moderate/advanced liver fibrosis measured by Fibroscan, together with highest plasma concentrations of most of the cytokines measured. The results showed positive correlation between HIV and HBV viral replication and liver fibrosis. The results suggest that there is persistent T-lymphocyte dysregulation and delayed immune recovery in ART-experienced HBV/HIV co-infected patients. However this does not appear to be associated with severity of liver fibrosis in this cohort. HAART used in HIV is also effective against HBV and may therefore have led to control of viral replication leading to better fibrosis scores compared to the HBV mono-infected patients. Moderate/advanced liver fibrosis in HBV-mono-infection may well be an indicator of poor access to HBV screening and treatment.AFRIKAANSE OPSOMMING : Geen Afrikaanse opsomming geskikbaar nieDoctora
The application of wastewater-based epidemiology to Hepatitis E virus in South Africa
No full textThesis (MSc)--Stellenbosch University, 2024.ENGLISH ABSTRACT: Background Hepatitis E virus (HEV) has a global presence, but the highest burden of disease is found in Africa and Asia. Unfortunately, in Sub-Saharan Africa, there is a gap in knowledge on the molecular epidemiology of the disease, as often serological methods only are applied. In recent years a high seroprevalence of the virus has been detected in populations in the Western Cape province. Evidence of viraemia has been published on a few South African patients from the Western Cape. Viral ribonucleic acid (RNA) was also detected in swine samples from an abattoir and in porcine meat products in Cape Town. Based on the existing literature, HEV genotype 3 has been detected in patients and swine samples. In this study, the aim was to determine whether HEV was circulating in communities in the Western Cape by testing wastewater extracts for the presence of HEV RNA. The study also sought to determine the HEV genotype in wastewater sample extracts. Methods One hundred and forty-three wastewater extracts were tested for the presence of HEV RNA using real-time polymerase chain reaction (PCR). Samples were sourced from four locations: two wastewater treatment works and sewer manholes from two Stellenbosch University residences. Nested reverse-transcriptase PCR (RTPCR) targeting three regions of the HEV genome was applied to samples which tested positive for HEV RNA. The sequenced regions were a portion of open reading frame (ORF) 2 covering 347 base pairs (bp), a 286 bp region of ORF1 and a 126 bp region of the overlapping ORF2/3. The generated PCR products were then sequenced with Sanger sequencing. The generated consensus sequences were placed in a phylogenetic tree with reference sequences for HEV genotypes 1 to 8, to determine which genotype is likely circulating in the selected communities. Results Out of the 143 wastewater samples, 130 valid results were generated. Out of 130, 21 (16.2%%) were positive and 109 (83.9%) were negative. Of the 21 positive samples, 5 (23.8%) were collected from Athlone wastewater treatment works (WWTW), 9 (42.9%) from Zandvliet WWTW, 1 (4.8%) from Meerhoff residence in Tygerberg and 6 (28.6%) from Metanoia residence in Stellenbosch. The positive samples had a median cycle threshold value of 37.9 (interquartile range: 36.7-39.7). Out of the 21 positive samples, 4 (19.1%) sequences were obtained from the ORF2/3 region. The sequences clustered most closely with a sequence from a South African patient and HEV genotype 3 reference sequences. Conclusions Based on the real-time PCR results, it appears that HEV is circulating among communities in the Western Cape province. Based on the detection of HEV genotype 3 in the wastewater samples, it suggests that zoonotic transmission may be the mostly likely route of infections. Further investigation to identify porcine and other food products which may be contaminated with HEV are necessary to break chains of transmission.AFRIKAANSE OPSOMMING: Agtergrond Hepatitis E virus (HEV) het ‘n wêreldwye teenwoordigheid, maar die hoogste siektelas is in Afrika en Asië ondervind. In Sub-Sahara Afrika, is daar ongelukkig ‘n gaping in die kennis van die molekulêre epidemiologie van die siekte, omdat serologiese metodes alleen dikwels gebruik word. ‘n Hoë seroprevalensie van die virus is onlangs in bevolkings in die Wes-Kaap provinsie opgespoor. Bewyse van viremie was in ‘n paar SuidAfrikaanse patiënte gedokumenteer. Virale ribonukleïensuur (RNS) was ook in vark monsters van ‘n slagpale en in varkvleisprodukte in Kaapstad bespeur. Gebaseer op die bestaande literatuur is HEV genotipe 3 in pasiënte en vark monsters bespeur. In hierdie studie was die doel om vas te stel of HEV in gemeenskappe in die Wes-Kaap sirkuleer deur afvalwaterekstrakte vir HEV RNS te toets. Hierdie studie het ook probeer om die HEV genotipe in afvalwatermonster ekstrakte te bepaal. Metodes Een honderd-drie-veertig afvalwaterektrakte was vir die teenwoordighied van HEV RNA getoets met intydse polimerase kettingsreaksie (PKR). Monsters was van vier liggins verkry: twee afvalwaterbehandelingswerke en riool mangate van twee Universiteit Stellenbos koshuise. Geneste omgekeerede transkripsie-PKR was gedoen op monsters wat positief getoets het vir HEV RNS. Die bepaalde streke was ‘n gedeelte van oop leesraam (OLR) 2 wat 347 base pair dek, ‘n 286 bp gedeelte van OLR1 en ‘n 126 bp OLR van OLR2/3. Die PKR produkte het toe volgorderbepaaling ondergaan met Sanger-volgorderbepaling. Die gegenereerde konsensus volgordes was dan met verwysing volgordes vir HEV genotipes een tot agt in ‘n filogenetiese boom geplaas. Dit was gebruik om die waarskynlike sirkulerende genotipe in die geselekteerde gemeenskappe te bepaal. Resultate Uit die die 143 afvalwatermonsters, het 130 geldige resultate gegenereer. Uit die 130 resultate, is 21 (16.2%) positief en 109 (83.9%) negatief. Uit die 21 positiewe monsters, is 5 (23.8%) van Athlone afvalwaterbehandelingswerke (AWBW) ingesamel, 9 (42.9%) van Zandvliet AWBW, 1(4.8%) van Meerhoff koshuis in Tygerberg en 6 (28.6%) van Metanoia koshuis in Stellenbos. Die positiewe monsters het ‘n mediaan waarde van 37.9 (interkwartielvariasiewydte: 36.7-39.7). Uit die 21 positiewe monsters, is 4 (19.1%) volgordes van die ORF2/3 streek verkry. Die volgordes het die nouste saam met ‘n positiewe volgorde van ‘n SuidAfrikaanse pasiënt en HEV genotipe 3 verwysingvolgordes gegroepeer. Gevolgtrekkings: Gebaseer op die intydse PKR resultate, blyk dit dat HEV onder gemeenskappe in the Wes-Kaap sirkuleer. Gebaseer op die opsoring van HEV genotipe 3 in die afvalwatermonsters, blyk dit dat soönotiese oordrag heel waarskynlik die roete van infeksies is. Verdere ondersoek is nodig om vark en ander kosprodukte wat dalk met HEV besmet is te identifiseer, om die kettings van oordrag te breek.Master
Implementation, evaluation and use of methods to identify SARS-CoV-2 genetic variants of significance
No full textThesis (MSc)--Stellenbosch University, 2023.ENGLISH SUMMARY: Background: The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants, designated as variants of concern (VOCs) by the World Health Organization (WHO) continue to threaten measures in place to contain the spread of the virus. Consequently, efforts have been made to intensify genomic surveillance to track and monitor the evolution and spread of SARS-CoV-2 VOCs to help inform public health interventions in a timely manner. However, whole genome sequencing (WGS) is expensive, has a longer turnaround time and requires expert bioinformatics analysis, making it unfeasible for near real-time monitoring and reporting of SARS-CoV-2 variants. There is a need for affordable variant screening methods for the rapid detection and differentiation of SARS-CoV-2 VOCs. Methods: Ten SARS-CoV-2 variant screening assays targeting SARS-CoV-2 Alpha, Beta, Delta and Omicron VOCs were used. The analytical sensitivity of the assays was assessed using RNA extracted from cell culture supernatants of isolates of the Beta and Delta VOCs and the limit of detection (LOD) and linearity of the assays were determined. Furthermore, the assays were used to screen for SARS-CoV-2 VOCs in 898 patient samples diagnosed with infection between November 2020 and January 2022. Screening results were validated against WGS to determine the clinical sensitivity, and specificity of variant screening assays, and the agreement between assays (using WGS as the gold standard) was reported as the kappa value. Lastly, the TaqMan SNP genotyping panel, TaqPath COVID-19, and ModularDx assays were implemented to estimate the proportion of SARS-CoV-2 VOCs that circulated between November 2020 and January 2022. Results: The SARS-COV-2 variant screening assay had a correlation coefficient between 0.98 and 0.99, indicating good linearity between the dilution and the corresponding average cycle threshold values (Ct-values) at each standard dilution. Of the 10 screening assays, the Smartchek B.1.351 assay had the lowest clinical sensitivity (86.4%) followed by the Allplex Variants I assay (95.5%). The sensitivity of the ModularDx assay and the TaqPath COVID-19 assays was 98.6% and 99.7%, respectively. Furthermore, the TaqMan mutation panel, Allplex Variants II, IV and Master assays were 100% sensitive. All assays demonstrated 100% specificity and moderate to high concordance in comparison with WGS. The predominant circulating variant before and during May 2021 was the Beta VOC, constituting 86.7%, 100% and 79.4% of samples screened in November and December 2020 and May 2021 respectively. The Delta VOC rapidly spread, displacing the Beta VOC in May 2021 and dominating from June until October 2021. In November, December 2021, and January 2022 the Omicron VOC predominated, with the proportion of samples resulting in failure of the S gene target to amplify, SGTF rising from 87.7% in November to 99.5% in December. Conclusion: This study demonstrated that SARS-CoV-2 variant screening assays can be used as rapid and affordable tools to monitor signature mutations in SARS-CoV-2 VOCs. In addition, they can be useful tools for scaling up SARS-CoV-2 genomic surveillance. However, they need to be regularly updated and cannot replace traditional sequencing methods, but rather serve as tools to complement sequencing in monitoring circulating SARS-CoV-2 VOCs.AFRIKAANSE OPSOMMING: Agtergrond: Die opkoms van akute respiratosie sindroom koronavirus (SARS-CoV-2) variante, wat deur die wereldgesondheidsorganisasie (WGO) as variante van kommer aangewys is, dreig steeds maatreels wat in plek is om die verspreiding van die virus te beperk. Gevolglik is pogings aangewend om genomiese toesig te versterk om die evolusie en verspreiding van SARS-CoV-2 variante van kommer (VOC's) op te spoor en te monitor om te help om openbare gesondheidsingrypings betyds in te lig. Heelgenoomvolgordebepaling is egter duur, het 'n langer omkeertyd en vereis kundige bioinformatika-analise en infrastruktuur, wat dit onprakties maak vir SARS-CoV-2 genomiese toesigstudies. Daar is 'n behoefte om vinnige en bekostigbare variante siftingsmetodes te ontwikkel om SARS-CoV-2 VOC's op te spoor en te onderskei en resultate betyds te rapporteer. Metodes: Tien toetse is in hierdie studie gebruik. Analitiese sensitiwiteit van die toetse is geassesseer deur gebruik te maak van ribonukleiensuur (RNS) wat uit selkultuursupernatant van variante kultuurisolate onttrek is en die limiet van opsporing en lineariteit van die toetse is bepaal. Verder is geevalueerde toetse gebruik om te sif vir die teenwoordigheid van SARS-CoV-2 VOC's in monsters wat tussen November 2020 en Januarie 2022 versamel is. Die resultate wat verkry is, is bekragtig teen heelgenoomvolgordes, die kliniese sensitiwiteit, spesifisiteit is bepaal, en die ooreenkoms tussen toetse (met heelgenoom-volgordebepaling as die goudstandaard) is bereken en as die kappa-waarde gerapporteer. Laastens is die TaqMan SNP genotiperingstoetse, TaqPath COVID-19 en ModularDx toetse gebruik om die verhouding SARS-CoV-2 VOC's in monsters wat tussen November 2020 en Januarie 2022 versamel is, te skat. Resultate: SARS-COV-2 variant siftingstoetse wat geevalueer is, het 'n korrelasiekoeffisient van 0.98 en 0.99 gehad, wat 'n goeie lineariteit tussen die verdunning en die ooreenstemmende gemiddelde siklus-drempel-waardes by elke standaardverdunning aandui. Nege siftingstoetse wat gebruik is om vir SARS-CoV-2 VOC's te sirkuleer wat tussen November 2020 en Januarie 2022 in 898 monsters gesirkuleer het. Die Smartchek B.1.351-toets het die laagste sensitiwiteit (86.4%) gevolg deur die Allplex Variants I-toets (95.5%). Die sensitiwiteit van die ModularDx- en TaqPath COVID-19-toetse was onderskeidelik 98.6% en 99.7%. Terwyl die TaqMan-mutasiepaneel, Allplex Variants II, IV en Master-toetse 100% sensitief was. Alle toetse het 100% spesifisiteit en matige tot hoe konkordansie getoon in vergelyking met heelgenoomvolgordes. Die oorheersende sirkulerende variant voor en gedurende Mei 2021 was die B.1.351 wat 86.7%, 100% en 79.4% uitmaak van monsters wat onderskeidelik in November en Desember 2020 en Mei 2021 gekeur is. Die B.1.617.2-lyn (Delta-variant) het vinnig versprei en die Beta-variant in Mei 2021 verplaas en daarna oorheers van Junie tot Oktober 2021. In November en Desember 2021 en Januarie 2022 was die omikronvariant oorheersend, met die proporsie van monsters wat daartoe gelei het dat die spike geen teiken mislukking (SGTF) van 87.7% in November 2021 tot 99.5% in Desember 2021 gestyg het. Gevolgtrekking: Hierdie studie was in staat om te demonstreer dat gevalideerde SARS-CoV-2 variant siftingstoetse gebruik kan word as vinnige en bekostigbare instrumente om handtekeningmutasie in SARS-CoV-2 VOC's te monitor. Boonop kan dit nuttige instrumente wees om SARS-CoV-2 genomiese toesig op te skaal. Hulle moet egter gereeld bygewerk word en kan nie tradisionele volgordebepalingsmetodes vervang nie, maar dien eerder as hulpmiddels om volgordebepaling aan te vul in die monitering van sirkulerende SARS-CoV-2 VOC's.Master
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Hepatitis B virus-associated hepatocellular carcinoma in South Africa in the era of HIV
No full textCITATION: Maponga, T. G., et al. 2020. Hepatitis B virus-associated hepatocellular carcinoma in South Africa in the era of HIV. BMC Gastroenterology, 20:226, doi:10.1186/s12876-020-01372-2.The original publication is available at https://bmcgastroenterol.biomedcentral.comBackground: Patients co-infected with hepatitis B virus (HBV) and the human immunodeficiency virus (HIV) are at
risk of developing hepatocellular carcinoma (HCC). In sub-Saharan Africa, the overlap between high HIV and HBV
prevalence may increase the incidence of HCC. This study investigated the impact of HBV/HIV co-infection on age
at presentation and survival of HCC.
Methods: Ethical approval was obtained to recruit, following informed written consent, patients diagnosed with
HCC at oncology units at four South African hospitals. Between December 2012 and August 2015, patients newly
diagnosed with HCC were recruited and provided demographic and clinical data and blood specimens. Patients
were tested for HBV, hepatitis C virus (HCV) and HIV. Survival data was available for a subset of patients.
Results: Of 107 HCC cases, 83 (78%) were male. Median age was 46 years (range 18 to 90 years), 68/106 (64%) were
HBsAg-positive, and 22/100 (22%) were HIV infected. Among HBV surface antigen (HBsAg)-positive HCC cases, 18/66
(27%) were HIV-infected compared to 3/34 (9%) among those that were HBsAg-negative (p = 0.04). A greater
proportion of HBV/HIV co-infected cases were female than HBV mono-infected (6/18, 33% vs 6/47, 13%; p = 0.005).
In addition, HBV/HIV co-infected females presented at a younger mean age (36.8 years) than HBV mono-infected
women (50.5 years) (p = 0.09). Median survival was 82 days among the HIV-infected HCC patients compared to 181
days among those without HIV (p = 0.15).
Conclusions: HCC is an important complication in the HIV/HBV infected patient. HIV-positive patients presented
with HCC at a younger age than HIV-negative patients, this effect appears to be greater in women. These data
provide more evidence supporting the call to address. HCC as a cause of morbidity and mortality in the HBV/HIV
co-infected patient population. (281 words).https://bmcgastroenterol.biomedcentral.com/articles/10.1186/s12876-020-01372-2Publisher's versio
OXSAHEP Project Report
No full textThis is a report for the 'OXSAHEP' (Oxford - South Africa - Hepatitis B' project.
OXSAHEP is a collaborative cohort established for the study of hepatitis B virus (HBV), undertaken with funding from Wellcome, supporting a collaboration between UK institutes (Oxford University and the Francis Crick Institute) and South African institutes (The University of Stellenbosch and The Univerisity of the Free State), from 2018 onwards. </p
Nascent technology ventures commercialization: A framework for capability development and business model transitions
No full textThis study examines the development of business models in early-stage technology startups and explores the impact of entrepreneurial decisions on the venture\u27s structure and success. The research sheds light on the importance of adapting business models to address complexity and uncertainty and examines the use of strategic decision-making logics by technology ventures. The findings reveal that early-stage technology ventures employ a combination of bricolage and effectuation logics, transitioning to a hybrid approach, which leads to greater success for firms with strong adaptive capabilities. The study also highlights the role of learning capabilities in the success of platform-based technology startups and demonstrates the importance of hybrid decision-making, experimentation, and agile pivoting in the adaptability of the business model. The study provides new insights into the commercialization process, regulation, and leadership in the growth trajectory of early-stage technology ventures, emphasizing the importance of decision-making dynamics, business model adaptation, and dynamic capabilities for success. The author argues that the interplay between business model regulation and organizational learning is essential for the commercialization and scaling of platform-based technology ventures and that utilizing both local and distant searches is key to unlocking the bottlenecks in the commercialization process. Overall, this study provides valuable insights into the centrality of business models, capabilities, and leadership in the growth trajectory of early-stage technology ventures
Viral hepatitis associated hepatocellular carcinoma on the African continent, the past, present, and future: a systematic review
No full textAbstract Background Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths in Africa. In Africa, the major causes of HCC include chronic infection with hepatitis B virus (HBV) and/or hepatitis C virus (HCV). Knowledge of the changes in the incidence of viral hepatitis-associated HCC over time and the factors responsible for such changes is key in informing policies for the prevention of viral hepatitis-associated HCC in Africa. Aim The study aimed to systematically summarize the changes in the prevalence of viral hepatitis among HCC patients and the overall effect of the prevalence of viral hepatitis on the incidence of HCC over the past four decades in Africa (1980–2019). Methods A literature search was conducted in MEDLINE (PubMed), Google Scholar, Science Direct, Scopus, Web of Science, and African wide web for articles published on viral hepatitis-associated HCC in Africa from 1980 to 2019. The abstracts of the articles were screened for eligibility and those meeting the inclusion criteria were retrieved and reviewed. Results A total of 272 studies were included in the analysis. Viral hepatitis-related HCC incidence changed by 1.17% (95% confidence interval (CI): 0.63–1.71, p < 0.001), 0.82% (95% CI: 0.45–1.18, p < 0.001), and 3.34% (95% CI: 2.44–4.25, p < 0.001) for every 1% change in the prevalence of HBV, HCV, and hepatitis D virus (HDV) respectively, per decade. The incidence of HBV-related HCC decreased by − 0.50% (95% CI: − 0.74 – − 0.25, p < 0.001) over the last 40 years, while HCV-related HCC increased. Conclusion Overall, the incidence of viral hepatitis-associated HCC has not declined, mainly due to no decline in the prevalence of HCV, HDV, and the high number of chronic hepatitis B carriers on the African continent. There is an urgent need for the allocation of resources for the implementation of treatment and preventive programs for HBV, HCV, HDV, and HCC in Africa. This systematic review is registered with PROSPERO®, number CRD42020169723
A putative hepatitis B virus sequence motif associated with hepatocellular carcinoma in South African adults
No full textIntroduction and ObjectivesChronic hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC). In African populations, HCC frequently presents at an advanced stage with poor outcomes. We applied whole genome sequencing (WGS) to compare HBV genomes in individuals with and without HCC.Materials and MethodsWe identified adults with HBV infection, with and without complicating HCC, in Cape Town, South Africa. We generated HBV WGS using pan-genotypic probe-based enrichment followed by Illumina sequencing.ResultsCompared to the non-HCC group, HCC patients were more likely to be male (p<0.0001), older (p=0.01), HIV-negative (p=0.006), and have higher HBV viral loads (p<0.0001). Among 19 HCC and 12 non-HCC patients for whom WGS was obtained, genotype A dominated (74%), of which 96% were subgenotype A1. PreS2 deletions (Δ38–55) were enriched in HBV sequences from HCC patients (n=7). The sequence motif most strongly associated with HCC comprised either a deletion or polymorphism at site T53 in PreS2 – collectively coined ‘non-T53’ – together with a basal core promoter (BCP) mutation G1764A (AUROC = 0.79).ConclusionsIn this setting, HBV sequence polymorphisms and deletions are associated with HCC, and ‘non-T53+G1764A’ represents a putative signature motif for HCC. Additional investigations are needed to disaggregate the impact of other demographic, clinical, and environmental influences, to ascertain the extent to which viral polymorphisms contribute to oncogenesis, and to determine whether HBV sequence is a useful biomarker for HCC risk stratification
Prevalence and risks of hepatitis E virus infection in blood donors from the Western Cape, South Africa
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