Browsing by Department "Division of Hepatology"

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    Evaluation of encapsulated liver cell spheroids in a fluidised-bed bioartificial liver for treatment of ischaemic acute liver failure in pigs in a translational setting
    (Public Library of Science, 2013) Selden, Clare; Spearman, Catherine Wendy; Kahn, Delawir; Miller, Malcolm; Figaji, Anthony; Erro, Eloy; Bundy, James; Massie, Isobel; Chalmers, Sherri-Ann; Arendse, Hiram
    Liver failure is an increasing problem. Donor-organ shortage results in patients dying before receiving a transplant. Since the liver can regenerate, alternative therapies providing temporary liver-support are sought. A bioartificial-liver would temporarily substitute function in liver failure buying time for liver regeneration/organ-procurement. Our aim: to develop a prototype bioartificial-liver-machine (BAL) comprising a human liver-derived cell-line, cultured to phenotypic competence and deliverable in a clinical setting to sites distant from its preparation. The objective of this study was to determine whether its use would improve functional parameters of liver failure in pigs with acute liver failure, to provide proof-of-principle. HepG2cells encapsulated in alginate-beads, proliferated in a fluidised-bed-bioreactor providing a biomass of 4-6×10 10 cells, were transported from preparation-laboratory to point-of-use operating theatre (6000miles) under perfluorodecalin at ambient temperature. Irreversible ischaemic liver failure was induced in anaesthetised pigs, after portal-systemic-shunt, by hepatic-artery-ligation. Biochemical parameters, intracranial pressure, and functional-clotting were measured in animals connected in an extracorporeal bioartificial-liver circuit. Efficacy was demonstrated comparing outcomes between animals connected to a circuit containing alginate-encapsulated cells (Cell-bead BAL), and those connected to circuit containing alginate capsules without cells (Empty-bead BAL). Cells of the biomass met regulatory standards for sterility and provenance. All animals developed progressive liver-failure after ischaemia induction. Efficacy of BAL was demonstrated since animals connected to a functional biomass (+ cells) had significantly smaller rises in intracranial pressure, lower ammonia levels, more bilirubin conjugation, improved acidosis and clotting restoration compared to animals connected to the circuit without cells. In the +cell group, human proteins accumulated in pigs' plasma. Delivery of biomass using a short-term cold-chain enabled transport and use without loss of function over 3days. Thus, a fluidised-bed bioreactor containing alginate-encapsulated HepG2cell-spheroids improved important parameters of acute liver failure in pigs. The system can readily be up-scaled and transported to point-of-use justifying development at clinical scale.
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    Global Disparities in Hepatitis B Elimination—A Focus on Africa
    (2022-01-03) Sonderup, Mark W.; Spearman, C. Wendy
    In 2016, WHO member states at the World Health Assembly adopted a Global Health Sector Strategy that included a policy of eliminating viral hepatitis. Clear targets were established to assist in achieving this by 2030. The strategy, while achievable, has exposed existing global disparities in healthcare systems and their ability to implement such policies. Compounding this, the regions with most disparity are also those where the hepatitis B prevalence and disease burden are the greatest. Foundational to hepatitis B elimination is the identification of both those with chronic infection and crucially pregnant women, and primary prevention through vaccination. Vaccination, including the birth dose and full three-dose coverage, is key, but complete mother-to-child transmission prevention includes reducing the maternal hepatitis B viral load in the third trimester where appropriate. Innovations and simplified tools exist in order to achieve elimination, but what is desperately required is the will to implement these strategies through the support of appropriate investment and funding. Without this, disparities will continue.
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    Hepatitis C prevalence in HIV infected heterosexual men and men who have sex with men
    (2018) Gogela, Neliswa Antonia; Sonderup, Mark Wayne; Spearman, C Wendy
    Background: Globally 1% of individuals are infected with hepatitis C virus (HCV). In South Africa (SA), the prevalence ranges between 0.3% - 1% with few prospective screening data available. Similarly, local data on transmission modes of HCV are limited but probably include parenteral routes and pre-1992 blood or blood product products. The risk of heterosexually transmission is low but is increased in men who have sex with men (MSM) with co- transmission risk of both HIV and HCV. Objectives: Given a limited local understanding, we sought to better understand HCV characteristics and prevalence in 2 groups of HIV-infected men. Methods: HIV positive men in the greater Cape Town metropolitan area were recruited. Sexual orientation was self-identified and demographic and other personal data obtained via a confidentially administered questionnaire. Participants were screened for HCV after a blood draw and positive HCV Ab tests were tested for HCV RNA. Risk factors associated with HCV seropositivity were determined. Results: Five hundred HIV positive men were recruited; 215 (43%) non-MSM and 285 (57%) MSM, with median age 36 years (IQR 20 – 64) and 37 years (IQR 21 – 56), in the MSM and non-MSM group, respectively, p = NS. Overall, 3.4% (n=17) screened HCV positive, 5.6% (n=16) MSM and 0.5% (n=1) non-MSM, with 82.4% viremic for HCV RNA. In respect to genotype (GT) distribution, 50% were infected with GT1, 14.3% GT4 and 35.7% were GT2. In terms of risk, MSM were more likely to have used drugs (54.4% vs. 30.2%, p<0.001) and to have used all five modes of drugs administration (13% of MSM vs. 0.5% of non- MSM for injected drugs, 36.1% vs. 2.3% inhaled, 10% vs. 0% for the rectal route, 48.1% vs. 28.8% for smoked and 27.4% vs. 2.3% for oral drugs). More MSM than non-MSM (46.3% vs. 16.7%) reported sex whilst using recreational drugs and similarly more MSM (21.4% vs. 14%) reported having sex with a sex worker (SW).Risk factors for HCV seropositivity included drug use history (odds ratio (OR) 6.28, 98% confidence interval (CI). 1.78 – 22.12: p=0.004) and in MSM, sex with SW (OR 5.5, 95% 2.06 – 14.68; p=0.001) or use of recreational drugs with sex (OR 6.88, 95% CI 2.21 -21.44; p=0.001). Conclusion: HCV prevalence in HIV positive MSM is higher than previously appreciated or documented in South Africa. Risk factors include injecting drug use, use of recreational drugs with sex and sex with SWs. Targeted interventions are required to address this emerging challenge to achieve the viral hepatitis elimination ideal by 2030.
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    Highlights from the 3rd international HIV/viral hepatitis Co-infection meeting - HIV/viral hepatitis: improving diagnosis, antiviral therapy and access
    (BioMed Central, 2017-04-20) Maponga, Tongai G; Matsha, Matteau Rachel; Morin, Sébastien; Scheibe, Andrew; Swan, Tracy; Andrieux-Meyer, Isabelle; Spearman, C Wendy; Klein, Marina B; Rockstroh, Jürgen Kurt
    The International AIDS Society convened the 3rd International HIV/Viral Hepatitis Co-Infection Meeting on 17 July 2016 as part of the pre-conference program preceding the 21st International AIDS Conference held in Durban, South Africa. The meeting brought together a diversity of scientific, technical and community interests to discuss opportunities and challenges for increased prevention, diagnosis and treatment of viral hepatitis in people living with HIV, particularly in low- and middle-income settings. The objectives of the meeting were: i. To review the latest therapeutic developments in viral hepatitis; ii. To identify challenges such as high cost of medications for hepatitis C virus (HCV) and risk of developing viral resistance, and successes, such as the provision of HCV treatment in community-based settings, movements to reduce drug costs and increasing access, in relation to scaling up diagnosis, screening, antiviral treatment and prevention of viral hepatitis; iii. To advance the agenda for elimination of viral hepatitis as a public health problem. Discussions centred around the six key interventions outlined by the World Health Organization Global Health Sector Strategy on Viral Hepatitis 2016–2021: hepatitis B virus (HBV) vaccination (including birth dose); safe injection practices plus safe blood; harm reduction among people who inject drugs; safer sex practices; hepatitis B treatment; and hepatitis C cure. This article summarizes the main issues and findings discussed during the pre-conference meeting. One of the recommendations from the meeting delegates is universal implementation of birth dose vaccination for HBV without further delay to prevent mother-to-child transmission of infection. There is also the need to implement screening and treatment of hepatitis among pregnant women. A call was made for concerted efforts to be put together by all stakeholders towards addressing some of the structural barriers, including criminalization of drug use, discrimination and stigma that people living with viral hepatitis face. Finally, the need for greater advocacy was highlighted to enable access to therapy of viral hepatitis at lower cost than currently prevails. Implementation of these resolutions will help in achieving the target of eliminating viral hepatitis as a public health threat.
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    Preventing hepatitis B and hepatocellular carcinoma in South Africa: The case for a birth-dose vaccine
    (2014) Spearman, C W N; Sonderup, Mark W
    Hepatitis B is a global public health issue, with some 2 billion people having current or past infection. In Africa, 65 million are chronically infected, an estimated 2.5 million of them in South Africa (SA). Hepatitis B and the associated complications of cirrhosis and hepatocellular carcinoma are entirely vaccine preventable. SA was one of the first ten countries in Africa to introduce universal hepatitis B vaccination in April 1995, but has no birth dose or catch-up programme. Although universal infant vaccination in SA has been successful in increasing population immunity to hepatitis B, improvements in terms of implementing protocols to screen all pregnant mothers for hepatitis B surface antigen (HBsAg) and ensuring full hepatitis B coverage, especially in rural areas, is justified. The World Health Organization has recommended a birth dose of hepatitis B vaccine in addition to the existing hepatitis B vaccine schedule in order to further decrease the risk of perinatal transmission. We recommend that SA implement a birth-dose vaccine into the existing schedule to attenuate the risk of perinatal transmission, prevent breakthrough infections and decrease HBsAg carriage in babies born to HIV-positive mothers.
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    South African guideline for the management of chronic hepatitis B: 2013
    (2013) Spearman, C W N; Sonderup, Mark W; Botha, J F; van der Merwe, S W; Song, E; Kassianides, C; Newton, K A; Hairwadzi, H N
    Hepatitis B remains a significant yet preventable health issue in South Africa. The introduction of the hepatitis B vaccine into the country some 18 years ago has demonstrated benefit, but the exposure to, and prevalence of chronic HBsAg positivity remain unacceptably high. Those with chronic hepatitis B virus infection have an elevated risk of developing cirrhosis with end-stage liver disease and a markedly elevated risk of hepatocellular carcinoma, independent of the presence of cirrhosis. The challenge in South Africa remains prevention through the universal vaccination coverage of all children and the identification of those with chronic hepatitis B virus infection. Over the last decade our understanding of hepatitis B and its behaviour and natural history in those with chronic infection has significantly improved. This understanding is key to identifying those who warrant further evaluation and therapy. A number of global societies have updated their guidelines in recent years. This document draws on these guidelines and serves to contextualise, for South Africa, practice guidelines for the management of chronic hepatitis B.