The African Liver Tissue Biorepository Consortium: Capacitating Population-Appropriate Drug Metabolism, Pharmacokinetics, and Pharmacogenetics Research in Drug Discovery and Development.

Pharmaceutical companies subject all new molecular entities to a series of in vitro metabolic characterizations that guide the selection and/or design of compounds predicted to have favorable pharmacokinetic properties in humans. Current drug metabolism research is based on liver tissue predominantly obtained from people of European origin, with limited access to tissue from people of African origin. Given the interindividual and interpopulation genomic variability in genes encoding drug-metabolizing enzymes, efficacy and safety of some drugs are poorly predicted for African populations. To address this gap, we have established the first comprehensive liver tissue biorepository inclusive of people of African origin. The African Liver Tissue Biorepository Consortium currently includes three institutions in South Africa and one in Zimbabwe, with plans to expand to other African countries. The program has collected 67 liver samples as of July 2023. DNA from the donors was genotyped for 120 variants in 46 pharmacogenes and revealed variants that are uniquely found in African populations, including the low-activity, African-specific CYP2C9*5 and *8 variants relevant to the metabolism of diclofenac. Larger liver tissue samples were used to isolate primary human hepatocytes. Viability of the hepatocytes and microsomal fractions was demonstrated by the activity of selected cytochrome P450s. This resource will be used to ensure the safety and efficacy of existing and new drugs in African populations. This will be done by characterizing compounds for properties such as drug clearance, metabolite and enzyme identification, and drug-drug and drug-gene interactions. SIGNIFICANCE STATEMENT: Standard optimization of the drug metabolism of new molecular entities in the pharmaceutical industry uses subcellular fractions such as microsomes and isolated primary hepatocytes, being done mainly with tissue from donors of European origin. Pharmacogenetics research has shown that variants in genes coding for drug-metabolizing enzymes have interindividual and interpopulation differences. We established an African liver tissue biorepository that will be useful in ensuring drug discovery and development research takes into account drug responses in people of African origin.

Successful ABO-incompatible living donor liver transplant for acute liver failure secondary to Hodgkin's Lymphoma in a child.

We present a case of pediatric ALF, secondary to hepatic HL, who underwent a successful ABOi living donor liver transplant. We believe this is the first such case reported in academic literature. HL with liver involvement is extremely rare and is not considered an indication for transplantation. The 12-year-old, male patient presented with a viral illness prodrome, and parvovirus was detected in pre-transplant laboratory cultures. He received an ABOi living donor liver graft followed by a course of plasma exchange and rituximab after which standard immunosuppression was used. The HL was diagnosed on hepatic biopsy post-transplant. Subsequently, the patient commenced six cycles of R-CHOP chemotherapy. During chemotherapy, we stopped tacrolimus and mycophenolate mofetil. Immunosuppression was maintained with corticosteroids in-between cycles. The patient is alive and reports good quality of life 1-year post-transplant. The HL is in remission. During the post-operative period, the patient experienced four episodes of neutropenia, a bile leak, and gram-negative sepsis. One episode of acute rejection has been treated. Although we did not initially transplant the patient for ALF secondary to HL, its subsequent diagnosis and the patient's response to management raises many issues that warrant consideration. While the findings from a single case cannot be generalized, this could be a "proof of concept" for liver transplantation in hepatic HL. We hope it will facilitate discussions and potentially expand therapeutic options available to this very small group patients.

Blood stream infections in children in the first year after liver transplantation at Wits Donald Gordon Medical Centre, South Africa.

Children who undergo liver transplantation and subsequently develop BSI are at risk for adverse outcomes. Research from high-income settings contrasts the dearth of information from transplant centers in low- and middle-income countries, such as South Africa. Therefore, this study from Johannesburg aimed to describe the clinical and demographic profile of children undergoing liver transplantation, and determine the incidence and pattern of BSI and associated risk factors for BSI during the first year after liver transplant. Pediatric liver transplants performed from 2005 to 2014 were reviewed. Descriptive analyses summarized donor, recipient, and post-transplant infection characteristics. Association between BSI and sex, cause of liver failure, age, nutritional status, PELD/MELD score, graft type, biliary complications, and acute rejection was determined by Fisher's exact test; and association with length of stay by Cox proportional hazards regression analysis. Survival estimates were determined by the Kaplan-Meier method. Sixty-five children received one transplant and four had repeat transplants, totaling 69 procedures. Twenty-nine BSI occurred in 19/69 (28%) procedures, mostly due to gram-negative organisms, namely Klebsiella species. Risk for BSI was independently associated with biliary atresia (44% BSI in BA compared to 17% in non-BA transplants; P = .014) and post-operative biliary complications (55% BSI in transplants with biliary complications compared to 15% in those without; P = .0013). One-year recipient and graft survival was 78% (CI 67%-86%) and 77% (CI 65%-85%), respectively. In Johannesburg, incident BSI, mostly from gram-negative bacteria, were associated with biliary atresia and post-operative biliary complications in children undergoing liver transplantation.

Minding the gap-Providing quality transplant care for South African children with acute liver failure.

Pediatric ALF is rare but life-threatening and may require urgent transplantation. In low and middle-income countries, access to transplantation is limited, deceased organ donation rates are low, and data on outcomes scarce. The Wits Donald Gordon Medical Centre, in Johannesburg, is one of only two centers in South Africa that perform pediatric liver transplant. We describe the etiology, clinical presentation, and outcomes of children undergoing liver transplant for ALF at our center over the past 14 years. We performed a retrospective chart review of all children undergoing liver transplantation for ALF from November 2005 to September 2019. Recipient data included demographics, clinical and biochemical characteristics pretransplant, post-operative complications, and survival. We conducted descriptive data analysis and used the Kaplan-Meier method for survival analysis. We performed 182 primary pediatric liver transplants. Of these, 27 (15%) were for ALF, mostly from acute hepatitis A infection (11/27;41%). Just over half of the grafts were from living donors (15/27;56%), and five grafts (5/27;19%) were ABO-incompatible. The most frequent post-transplant complications were biliary leaks (9/27;33%). There were two cases of hepatic artery thrombosis (2/27;7%), one of whom required re-transplantation. Unadjusted patient and graft survival at one and 3 years were the same, at 81% (95% CI 61%-92%) and 78% (95% CI 57%-89%), respectively. At WDGMC, our outcomes for children who undergo liver transplantation for ALF are excellent. We found workable solutions that effectively addressed our pervasive organ shortages without compromising patient outcomes.

HIV and Solid Organ Transplantation: Where Are we Now.

PURPOSE OF REVIEW: We review the international evolution of HIV and solid organ transplantation over 30 years. We emphasise recent developments in solid organ transplantation from HIV-infected to HIV-uninfected individuals, and their implications. RECENT FINDINGS: In 2017, Johannesburg, South Africa, a life-saving partial liver transplant from an HIV-infected mother to her HIV-uninfected child was performed. This procedure laid the foundation not only for consideration of HIV-infected individuals as living donors, but also for the possibility that HIV-uninfected individuals could receive organs from HIV-infected donors. Recent advances in this field are inclusion of HIV-infected individuals as living organ donors and the possibility of offering HIV-uninfected individuals organs from HIV-infected donors who are well-controlled on combination antiretroviral therapy (cART). The large number of HIV-infected individuals on cART is an unutilised source of otherwise eligible living organ donors. HIV-positive-to-HIV-negative organ transplantation has become a reality, providing possible new therapeutic options to address extreme organ shortages.

Needs must: living donor liver transplantation from an HIV-positive mother to her HIV-negative child in Johannesburg, South Africa.

The world's first living donor liver transplant from an HIV-positive mother to her HIV-negative child, performed by our team in Johannesburg, South Africa (SA) in 2017, was necessitated by disease profile and health system challenges. In our country, we have a major shortage of donor organs, which compels us to consider innovative solutions to save lives. Simultaneously, the transition of the HIV pandemic, from a death sentence to a chronic illness with excellent survival on treatment required us to rethink our policies regarding HIV infection and living donor liver transplantation . Although HIV infection in the donor is internationally considered an absolute contraindication for transplant to an HIV-negative recipient, there have been a very small number of unintentional transplants from HIV-positive deceased donors to HIV-negative recipients. These transplant recipients do well on antiretroviral medication and their graft survival is not compromised. We have had a number of HIV-positive parents in our setting express a desire to be living liver donors for their critically ill children. Declining these parents as living donors has become increasingly unjustifiable given the very small deceased donor pool in SA; and because many of these parents are virally suppressed and would otherwise fulfil our eligibility criteria as living donors. This paper discusses the evolution of HIV and transplantation in SA, highlights some of the primary ethical considerations for us when embarking on this case and considers the new ethical issues that have arisen since we undertook this transplant.

A Qualitative Analysis of South African Health Professionals' Discussion on Distrust and Unwillingness to Refer Organ Donors.

INTRODUCTION: South Africa is faced with very low deceased organ donor numbers. Often, sociocultural practices, which are thought to be fundamentally opposed to deceased organ donation, are hailed as the cause. However, other factors such as context, social perceptions, and clinical environment may play a role. AIM: The aim of this article is to present research that explored communication in organ transplant and identified barriers to organ donation decisions in a province of South Africa. METHODS: Qualitative methods were used. Thirty semistructured interviews with transplant professionals and 2 focus groups with transplant coordinators took place across 6 health institutions in Gauteng Province. RESULTS: Barriers that may prevent transplant professionals from referring potential donors were identified: The wider public and transplant professionals may be suspicious of biomedicine and have a perception that people could be killed for their organs. Organ donation was sometimes framed as "murder," "killing," or a "bunch of vultures." Doctors may be unwilling to refer brain-dead patients, as this was seen as failing in one's professional duty to cure the patient. The role of sociocultural practices was inconclusive, with the sample divided based on the extent of their influence. CONCLUSION: Low donor numbers may be a manifestation of barriers to referral in the clinical setting. These barriers interplay in a context of suspicion and are framed by a clinical transplant discourse that is sometimes loaded with negative connotation. Sociocultural practices are influential, but they may not be the overriding cause of low donor numbers.

Opt-in or opt-out to increase organ donation in South Africa? Appraising proposed strategies using an empirical ethics analysis.

Utilising empirical ethics analysis, we evaluate the merits of systems proposed to increase deceased organ donation in South Africa (SA). We conclude that SA should maintain its soft opt-in policy, and enhance it with 'required transplant referral' in order to maximise donor numbers within an ethically and legally acceptable framework. In SA, as is the case worldwide, the demand for donor organs far exceeds the supply thereof. Currently utilising a soft opt-in system, SA faces the challenge of how to increase donor numbers in a context which is imbued with inequalities in access to healthcare, multiplicitous personal beliefs and practices, distrust of organ transplant and varying levels of education and health literacy. We argue that a hard opt-in, opt-out or mandated consent system would be problematic, and we present empirical data from Gauteng Province illustrating barriers to ethically sound practice in soft consent systems. Ultimately, we argue that in spite of some limitations, a soft opt-in system is most realistic for SA because its implementation does not require extensive public education campaigns at national level, and it does not threaten to further erode trust at a clinical level. However, to circumvent some of the clinical-level barriers identified in our empirical study, we propose a contextually sensitive option for "enabling" soft opt-in through "required transplant referral". We argue that this system is legally defensible, enhances ethical practice and could also increase donor numbers as it has in many other countries.

Ethics and Rationing Access to Dialysis in Resource-Limited Settings: The Consequences of Refusing a Renal Transplant in the South African State Sector.

Resource constraints in developing countries compel policy makers to ration the provision of healthcare services. This article examines one such set of Guidelines: A patient dialysing in the state sector in South Africa may not refuse renal transplantation when a kidney becomes available. Refusal of transplantation can lead to exclusion from the state-funded dialysis programme. This Guideline is legally acceptable as related to Constitutional stipulations which allow for rationing healthcare resources in South Africa. Evaluating the ethical merit of the Guideline, and exploring the ethical dilemma it poses, proves a more complex task. We examine the actions of healthcare professionals as constrained by the Guideline. From a best interests framework, we argue that in these circumstances directing patient decision making (pressurising a patient to undergo renal transplantation) is not necessarily unethical or unacceptably paternalistic. We then scrutinise the guideline itself through several different ethical 'lenses'. Here, we argue that bioethics does not provide a definitive answer as to the moral merit of rationing dialysis under these circumstances, however it can be considered just in this context. We conclude by examining a potential pitfall of the Guideline: Unwilling transplant recipients may not comply with immunosuppressive medication, which raises questions for policies based on resource management and rationing.

Communication in Healthcare: Global challenges in the 21st Century.

This article explores the communication challenges brought about by the digital revolution in the 21st century for healthcare professionals internationally. It particularly focuses on the use of content-generating and sharing platforms like social media. Globally, healthcare has been irrevocably altered by digital innovation and health professionals deploy an extensive range of social media and web-based tools on a daily basis. However, many healthcare professionals use these platforms in a regulatory vacuum-where there may not be specific legal or ethical guidance-and without an appreciation of the associated risks. Given the special protections afforded to the practitioner-patient relationship, and the importance of a health practitioners' reputation, it is vital that we understand how to traverse the many ethical and legal challenges of the digital interaction. A comprehensive set of recommendations (see "Guidelines for Good Digital Citizenship in the Health Professions" on page 5 ff.) to keep practitioners out of trouble is provided. These hinge on the notion of being a "good person and a good doctor" as a formative maxim for ethical and legal safety. The constituents of publication, and the consequences of falling foul of acceptable publication standards on social media, are specifically discussed. "Publication" involves sharing content with a third party, or a group of people, and social media refers to platforms on which content can be shared with more than one person. Hence, most information that we post on social media can be considered as "published," and as such may attach liability for health professionals who do not use these platforms with requisite care and sufficient forethought.

Emphasising Organisational Routine: A Qualitative Study of Patient and Health Professional Experiences of Inpatient Oncology Care.

BACKGROUND: Although the experience of hospitalisation for cancer management has been widely researched, such research from the African sub-continent is limited. OBJECTIVE: This study explored experiences of patient care in a tertiary, inpatient oncology setting in urban South Africa, from the point of view of patients and health professionals. METHODS: In-depth interviews and focus groups were conducted with participants. Participants included oncology inpatients, oncologists, nurses and nursing management (N = 46) at an oncology unit in Johannesburg, South Africa. Data were analysed by a multidisciplinary research group using reflexive thematic analysis principles. RESULTS: Our results suggest that barriers to establishing effective organisational routines included communication breakdowns between patients and healthcare providers, a lack of predictability in interactions with doctors, deficient access to information and diminished confidence in nurses. CONCLUSIONS: Oncology inpatients may not feel in control of their circumstances, in part due to lacking routine in the hospital setting. Ironically, nurses, who are often at the frontline of patient management, appear to be underutilised or disabled by the healthcare system as conveyors of information. IMPLICATIONS FOR PRACTICE: Robust organisational routines for oncology inpatients may be a good mechanism for allaying uncertainty and conferring a sense of control. Nursing staff, as the individuals with the most direct patient contact, could be instrumental in nurturing organisational routines towards improving patient perceptions of care.

Coronavirus Host Genomics Study: South Africa (COVIGen-SA).

Host genetic factors are known to modify the susceptibility, severity, and outcomes of COVID-19 and vary across populations. However, continental Africans are yet to be adequately represented in such studies despite the importance of genetic factors in understanding Africa's response to the pandemic. We describe the development of a research resource for coronavirus host genomics studies in South Africa known as COVIGen-SA-a multicollaborator strategic partnership designed to provide harmonised demographic, clinical, and genetic information specific to Black South Africans with COVID-19. Over 2,000 participants have been recruited to date. Preliminary results on 1,354 SARS-CoV-2 positive participants from four participating studies showed that 64.7% were female, 333 had severe disease, and 329 were people living with HIV. Through this resource, we aim to provide insights into host genetic factors relevant to African-ancestry populations, using both genome-wide association testing and targeted sequencing of important genomic loci. This project will promote and enhance partnerships, build skills, and develop resources needed to address the COVID-19 burden and associated risk factors in South African communities.

Assessing Global Organ Donation Policies: Opt-In vs Opt-Out.

This paper argues that there is little difference between opt-in and opt-out organ donation systems for increasing donor numbers when used in isolation. Independently diverting to an opt-out system confers no obvious advantage and can harm efforts to bolster donations. Rather, it is essential to address barriers to organ donation on several levels along with a switch in system. Moreover, for many countries, it may be more beneficial to adequately capacitate the donation system already in place, rather than entertain a significant change with its attendant resource requirements. For decades, the international transplant community has been involved in vigorous debate as to the merits of moving from default opt-in systems to opt-out policies to grow organ donor numbers and better meet the ever-increasing demand for lifesaving transplants. Opt-out is certainly en vogue, with Wales, England and Nova Scotia recently switching over, Scotland due to become opt-out in March 2021 and Northern Ireland and Canada seriously considering a similar move. Thanks to several countries making the switch from opt-in to opt-out over the last 20-30 years, there are sets of robust longitudinal data that aid in analysing the efficacy of donation systems. However, these data are often contradictory and largely inconclusive, suggesting other factors may be in play. This paper reviews some emerging trends in opt-in versus opt-out organ donation policies and considers recent data that elucidates some of the main contentions across each. Ethical frameworks underpinning donation systems, such as informed consent, trust and transparency, are discussed in detail. Substantial time is also devoted to opt-in vs opt-out systems in developing countries, which tend to be excluded from many analyses, and where the challenges faced are magnified by socio-economic constraints. This constitutes a major gap in recently published literature, as developing countries often lag far behind their developed counterparts in donor and transplant numbers.

A pilot study evaluating an intervention designed to raise awareness of clinical trials among potential participants in the developing world.

BACKGROUND: This pilot study evaluated the speaking book 'What it means to be part of a clinical trial'. The book aims at empowering populations with information on their rights and responsibilities when enrolled in clinical research. Wide publication of the book-at significant cost-is anticipated. It is important that the book is evaluated within the communities for whom it is intended, and the necessary changes (if any) are made, before translation and large-scale publication takes place. OBJECTIVE: The objective of the study was to measure the efficacy and ease of use of the book. METHODS: Participants were recruited from a catering company. Participants were questioned on their knowledge of clinical trials and were then given the book. Instructions for use of the book were given to one group ('experimental' group). The other group ('control' group) was not given any instructions. A week later, the investigators returned, repeated the knowledge questions and asked 'ease of use' questions. RESULTS: A two-way repeated measure of covariants showed a statistically significant positive increase in knowledge of clinical trials among the intervention group (p=0.02). Results for the control group displayed trends that were not statistically significant. Percentage analysis of 'ease of use' questions proved that the book is easy to use, although some changes would be beneficial. CONCLUSION: This study revealed that the speaking book is easy to use. It significantly increased knowledge of clinical trials among the study sample if instructions on use of the book were provided.

Liver Transplant for Nonresectable Colorectal Cancer Liver Metastases in South Africa: A Single-Center Case Series.

OBJECTIVES: Publication in 2013 of the first Secondary Cancer cohort study returned attention to liver transplant for nonresectable colorectal cancer, demonstrating excellent outcomes for a procedure that was historically contraindicated. The Wits Donald Gordon Medical Centre in Johannesburg, South Africa, hosts the largest liver transplant program in sub-Saharan Africa. The persistent shortage of deceased donor organs in our setting has compelled us to innovate solutions unique to our context, which allows us to perform as many transplants as possible and maximize our resource utilization. Therefore, we initiated a research study to transplant organs in patients with nonresectable colorectal carcinoma with expanded criteria using marginal deceased donor organs that would otherwise have been discarded. MATERIALS AND METHODS: Institutional Review Board approval was obtained for this study. We used criteria from the 2013 Secondary Cancer cohort study to determine eligibility of patients with nonresectable colorectal carcinoma for liver transplant. Unlike the study from 2013, we utilized expanded criteria and marginal liver allografts for transplant. RESULTS: Five patients have undergone liver transplant for nonresectable colorectal carcinoma. At a median follow-up of 36 months (range, 10-52 months), 4 of the 5 (80%) patients are alive. The patient who died had progressive disease on chemotherapy pretransplant and was the only patient who tested positive for the Kirsten rat sarcoma viral oncogene homolog mutant. Recurrence occurred in all patients at a median time of 6 months after transplant (range, 3-13 months). CONCLUSIONS: To our knowledge, this is the only published case series of patients undergoing liver transplant for nonresectable colorectal carcinoma in Africa and is internationally unique in its use of expanded criteria and marginal grafts for this type of transplant. Despite the use of such grafts in our recipients, thus far, these outcomes align with those of the 2013 Secondary Cancer cohort studies from Norway.

Methods and reporting of kidney function: a systematic review of studies from sub-Saharan Africa.

Globally, chronic kidney disease (CKD) is an emerging public health challenge but accurate data on its true prevalence are scarce, particularly in poorly resourced regions such as sub-Saharan Africa (SSA). Limited funding for population-based studies, poor laboratory infrastructure and the absence of a validated estimating equation for kidney function in Africans are contributing factors. Consequently, most available studies used to estimate population prevalence are hospital-based, with small samples of participants who are at high risk for kidney disease. While serum creatinine is most commonly used to estimate glomerular filtration, there is considerable potential bias in the measurement of creatinine that might lead to inaccurate estimates of kidney disease at individual and population level. To address this, the Laboratory Working Group of the National Kidney Disease Education Program published recommendations in 2006 to standardize the laboratory measurement of creatinine. The primary objective of this review was to appraise implementation of these recommendations in studies conducted in SSA after 2006. Secondary objectives were to assess bias relating to choice of estimating equations for assessing glomerular function in Africans and to evaluate use of recommended diagnostic criteria for CKD. This study was registered with Prospero (CRD42017068151), and using PubMed, African Journals Online and Web of Science, 5845 abstracts were reviewed and 252 full-text articles included for narrative analysis. Overall, two-thirds of studies did not report laboratory methods for creatinine measurement and just over 80% did not report whether their creatinine measurement was isotope dilution mass spectroscopy (IDMS) traceable. For those reporting a method, Jaffe was the most common (93%). The four-variable Modification of Diet in Renal Disease (4-v MDRD) equation was most frequently used (42%), followed by the CKD Epidemiology Collaboration (CKD-EPI) equation for creatinine (26%). For the 4-v MDRD equation and CKD-EPI equations, respectively, one-third to one half of studies clarified use of the coefficient for African-American (AA) ethnicity. When reporting CKD prevalence, <15% of studies fulfilled Kidney Disease: Improving Global Outcomes criteria and even fewer used a population-based sample. Six studies compared performance of estimating equations to measured glomerular filtration rate (GFR) demonstrating that coefficients for AA ethnicity used in the 4-v MDRD and the CKD-EPI equations overestimated GFR in Africans. To improve on reporting in future studies, we propose an 'easy to use' checklist that will standardize reporting of kidney function and improve the quality of studies in the region. This research contributes some understanding of the factors requiring attention to ensure accurate assessment of the burden of kidney disease in SSA. Many of these factors are difficult to address and extend beyond individual researchers to health systems and governmental policy, but understanding the burden of kidney disease is a critical first step to informing an integrated public health response that would provide appropriate screening, prevention and management of kidney disease in countries from SSA. This is particularly relevant as CKD is a common pathway in both infectious and non-communicable diseases, and multimorbidity is now commonplace, and even more so when those living with severe kidney disease have limited or no access to renal replacement therapy.

Non-referral of potential organ donors in South Africa: insights, challenges and ethical dilemmas.

Traditionally, minimal potential organ donor referrals emanate from general medicine departments. We use a clinical vignette to draw attention to challenges related to referral of potential organ donors from general internal medicine departments. In addition, we provide potential solutions to overcome challenges and reflect on the ethical issues of non-referral of potential organ donors. It is hoped that this paper will increase the awareness of organ donation in the medical fraternity in Africa and thus mitigate critical shortages of organs for transplantation.

Living donor liver transplant from an HIV-positive mother to her HIV-negative child: opening up new therapeutic options.

OBJECTIVE: Transplant a liver from an HIV-positive mother to her HIV-negative child to save the child's life. DESIGN: A unique case of living donor liver transplantation from an HIV-positive mother to her HIV-negative child in South Africa. Two aspects of this case are ground-breaking. First, it involves living donation by someone who is HIV-positive and second it involves controlled transplant of an organ from an HIV-positive donor into an HIV-negative recipient, with the potential to prevent infection in the recipient. METHODS: Standard surgical procedure for living donor liver transplantation at our centre was followed. HIV-prophylaxis was administered preoperatively. Extensive, ultrasensitive HIV testing, over and above standard diagnostic assays, was undertaken to investigate recipient serostatus and is ongoing. RESULTS: Both mother and child are well, over 1 year posttransplantation. HIV seroconversion in our recipient was detected with serological testing at day 43 posttransplant. However, a decline in HIV antibody titres approaching undetectable levels is now being observed. No plasma, or cell-associated HIV-1 DNA has been detected in the recipient at any time-point since transplant. CONCLUSION: This case potentially opens up a new living liver donor pool which might have clinical relevance in countries where there is a high burden of HIV and a limited number of deceased donor organs or limited access to transplantation. However, our recipient's HIV status is equivocal at present and additional investigation regarding seroconversion events in this unique profile is ongoing.

Challenges in Expanding Access to Dialysis in South Africa-Expensive Modalities, Cost Constraints and Human Rights.

South Africa is a country with two distinct health sectors, which are both characterised by inequalities. Within this context, patients with end stage renal disease face unique and sometimes impenetrable barriers to accessing dialysis. There are a number of reasons for this situation. These include: the South African government's endorsement of discordant, unequal policies, which disadvantage the most vulnerable; a lack of robust national guidelines; and divisive rationing practices, which are ad hoc and place the burden of responsibility for rationing dialysis on the clinician. In this paper, we trace the socio-economic mechanisms of how we have come to be in this situation, and overlay this with a detailed examination of South African legislation. Finally, we make comprehensive practical recommendations for rectifying the situation, which include engagement with key stakeholders, public-private partnerships, and more equitable funding mechanisms.