Increasing deceased organ donor numbers in Johannesburg, South Africa: 18-month results of the Wits Transplant Procurement Model.

In 2016, deceased-donor organ procurement at Wits Transplant, based at Wits Donald Gordon Medical Centre in Johannesburg, South Africa (SA), was in a state of crisis. As it is the largest-volume solid-organ transplant unit in SA, and as we aspire to provide transplant services of an international standard, the time to address our procurement practice had come. The number of deceased donors consented through our centre was very low, and we needed a radical change to improve our performance. This article describes the Wits Transplant Procurement Model - the result of our work to improve procurement at our centre. The model has two core phases, one to increase referrals and the other to improve our consent rates. Within these phases there are several initiatives. To improve referrals, the threefold approach of procurement management, acknowledgement and resource utilisation was developed. In order to 'convert' referrals into consents, we established the Wits Transplant 'Family Approach to Consent for Transplant Strategy' (FACTS). Since initiation of the Wits Transplant Procurement Model, both our referral numbers from targeted hospitals and our conversion rates have increased. Referrals from targeted hospitals increased by 54% (from 31 to 57). Our consent rate increased from 25% (n=6) to 73% (n=35) after the initiation of Wits Transplant FACTS. We hope that other transplant centres in SA and further afield in the region will find this article helpful, and to this end we have created a handbook on the Wits Transplant Procurement Model that is freely available for download (http://www.dgmc.co.za/docs/Wits-Transplant-Procurement-Handbook.pdf).

Reimagining liver transplantation in South Africa: A model for justice, equity and capacity building - the Wits Donald Gordon Medical Centre experience.

The challenge of providing effective and integrated liver transplant services across South Africa's two socioeconomically disparate healthcare sectors has been faced by Wits Donald Gordon Medical Centre (WDGMC) since 2004. WDGMC is a private academic hospital in Johannesburg and serves to supplement the specialist and subspecialist medical training provided by the University of the Witwatersrand. Over the past 14 years, our liver transplant programme has evolved from a sometimes fractured service into the largest-volume liver centre in sub-Saharan Africa. The growth of our programme has been the result of a number of innovative strategies tailored to the unique nature of transplant service provision. These include an employment model for doctors, a robust training and research programme, and a collaboration with the Gauteng Department of Health (GDoH) that allows us to provide liver transplantation to state sector patients and promotes equality. We have also encountered numerous challenges, and these continue, especially in our endeavour to make access to liver transplantation equitable but also an economically viable option for our hospital. In this article, we detail the liver transplant model at WDGMC, fully outlining the successes, challenges and innovations that have arisen through considering the provision of transplant services from a different perspective. We focus particularly on the collaboration with the GDoH, which is unique and may serve as a valuable source of information for others wishing to establish similar partnerships, especially as National Health Insurance comes into effect.

Adult liver transplantation in Johannesburg, South Africa (2004 - 2016): Balancing good outcomes, constrained resources and limited donors.

BACKGROUND: Liver transplantation is the standard of care for the treatment of liver failure worldwide, yet millions of people living in sub-Saharan Africa remain without access to these services. South Africa (SA) has two liver transplant centres, one in Cape Town and the other in Johannesburg, where Wits Donald Gordon Medical Centre (WDGMC) started an adult liver transplant programme in 2004. OBJECTIVES:  To describe the outcomes of the adult liver transplant programme at WDGMC. METHODS:  This was a retrospective review of all adult orthotopic liver transplants performed at WDGMC from 16 August 2004 to 30 June 2016 with a minimum follow-up of 6 months. The primary outcome was recipient and graft survival and the effect of covariates on survival. Kaplan-Meier survival analysis included all adults who underwent their first transplant for end-stage liver disease (ESLD) (N=275). Proportional hazards regression analysis using hazard ratios (HRs) was conducted to determine which covariates were associated with a significantly increased risk of mortality. RESULTS:  A total of 297 deceased-donor liver transplants were performed during the study period; 19/297 (6.4%) were for acute liver failure (ALF) and the remainder were for ESLD. The median age of recipients was 51 years (interquartile range 41 - 59), and two-thirds were male. The most common cause of ESLD was primary sclerosing cholangitis. The median follow-up was 3.2 years, and recipient survival was characterised in the following intervals: 90 days = 87.6% (95% confidence interval (CI) 83.1 - 91.0), 1 year = 81.7% (95% CI 76.6 - 85.8), and 5 years = 71.0% (95% CI 64.5 - 76.5). Allograft survival was similar: 90 days = 85.8% (95% CI 81.1 - 89.4), 1 year = 81.0% (95% CI 75.8 - 85.2), and 5 years = 69.1% (95% CI 62.6 - 74.7). The most significant covariates that impacted on mortality were postoperative biliary leaks (HR 2.0 (95% CI 1.05 - 3.80)), recipient age >60 years at time of transplant (HR 2.06 (95% CI 1.06 - 3.99)), theatre time >8  hours (HR 3.13 (95% CI 1.79 - 5.48)), and hepatic artery thrombosis (HR 5.58 (95% CI 3.09 - 10.08)). The most common infectious cause of death was invasive fungal infection. CONCLUSIONS:  This study demonstrates that outcomes of the adult orthotopic liver transplant programme at WDGMC are comparable with international transplant centres. Management of biliary complications, early hepatic artery thrombosis and post-transplant infections needs to be improved. Access to liver transplantation services is still extremely limited, but can be improved by addressing the national shortage of deceased donors and establishing a national regulatory body for solid-organ transplantation in SA.

Kidney transplant outcomes following the introduction of hand-assisted laparoscopic living donor nephrectomy: a comparison of recipient groups.

BACKGROUND: Laparoscopic donor nephrectomy has become the procedure of choice for living donor kidney transplantation in many centres. We report on our experience with hand-assisted laparoscopic donor nephrectomy (HALDN). We concentrated on graft function and postoperative surgical complications in the recipient population, and compared outcomes to a similar recipient group who had received kidneys procured by open living-donor nephrectomy (OLDN). METHOD: Following the receipt of institutional approval, the files of all patients who received a kidney transplant between September 2008 and June 2011 were reviewed. One hundred patients with end-stage renal disease received kidney transplantations from living donors. OLDN was performed in 65 donors, and 35 underwent HALDN. Delayed graft function (DGF) and postoperative complications were recorded. RESULTS: Six adverse events were reported, during which five patients presented with DGF. One DGF was reported in the HALDN group, and four in the OLDN group. The morbidity in the HALDN group (1/35, 3%) was a graft rupture secondary to acute rejection which required exploration and transplant nephrectomy. Reoperation was required in five patients in the OLDN group (5/65, 8%). This amounted to overall morbidity of 6%, with no recipient mortalities. CONCLUSION: As previously documented, HALDN is safe for the donor, and not inferior to OLDN. In this study, it was associated with neither an increased incidence of DGF, nor a higher complication rate in the transplant recipient, when compared to the cohort that received a kidney harvested using the OLDN technique.

South African guideline for the management of chronic hepatitis B: 2013.

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.

Guideline for the diagnosis and treatment of chronic pancreatitis.

BACKGROUND: Chronic pancreatitis (CP) is defined as a continuing inflammatory disease of the pancreas characterised by irreversible morphological changes, often associated with pain and with the loss of exocrine and/or endocrine function that may be clinically relevant. Alcohol is the predominant cause of CP in the western world and is particularly prevalent in South Africa, especially in the indigent patient. CP ranks high among intractable diseases of the gastrointestinal tract. The tendency for substance abuse in the alcohol-induced group poses major psychological and socio-economic problems. OBJECTIVE: CP is a disease with significant clinical and pathological heterogeneity. Level 1 evidence to support definitive guidelines for diagnosis, medical management and interventional therapy is lacking. Despite this paucity of robust scientific evidence, it is important to provide some assistance based on the best available evidence as to the current standard of care for CP in the South African context; this will aid all involved in the management of the disease, and includes clinicians, health care managers and funders. SCOPE: The guidelines were developed as recommendations addressing the diagnosis, medical management and interventions, both endoscopic and surgical, for the management of a very complex and heterogeneous disease of the pancreas. The recommendations are particularly relevant in the South African context where the predominant patho-aetiological agents are alcohol-associated with smoking. RECOMMENDATIONS: The guidelines provide clear recommendations regarding the diagnostic modalities available, both imaging (which includes MRI and endoscopic ultrasound (EUS)) and pancreatic function tests. The section on medical management makes recommendations on the use of analgesics, enzyme replacement and other therapeutic options in the non-interventional management of the majority of patients with CP. The section on interventional procedures identifies the indications and options available for the interventional management of both uncomplicated and complicated CP. The role of endoscopic and surgical modalities is defined, but it is in this context especially that the best available evidence, combined with the experience of the group, influenced the recommendations put forward. Owing to the lack of evidence and the complexity of the disease, it is recommended that, where possible, CP is managed in the context of a multidisciplinary team. VALIDATION: The guidelines are based on best practice principles determined by the available evidence and the opinions of the group, which comprised 7 medical and surgical gastroenterologists with significant experience in dealing with patients with chronic pancreatitis in the South African context. The group convened between May 2009 and August 2010 under the auspices of the Hepato-Pancreatico-Biliary Association of South Africa (HPBASA) and the South African Gastroenterology Society (SAGES), and the guidelines are the result of broad consensus within this group. The draft was presented to other experts in this field of endeavour to ensure broader participation and consensus. PLANS FOR GUIDELINE REVISION: HPBASA and SAGES will publish a revised modification of the recommendations when new levels 1 and 2 evidence data are published.

The use of a cyclosporin-ketoconazole combination: making renal transplantation affordable in developing countries.

OBJECTIVES: The costs of immunosuppressive drugs in renal transplant recipients remains prohibitively high. Ketoconazole (KZ) has, in limited studies, been shown to significantly reduce the dose of cyclosporin (CyA) after renal transplantation. We report our long-term experience with the use of KZ in a large group of renal transplant recipients. Although this study was not a formal health economic assessment, we undertook a cost-saving analysis of the CyA-KZ combination usage. METHODS: The 170 patients (174 transplants) undergoing renal transplantation between 1991 and 1997 included in the study received CyA (10 mg/kg/day), prednisone (30 mg/day) and azathioprine (100 mg/day) in the immediate perioperative period. At 1 month post-transplantation, KZ (100 mg twice daily) was added and the CyA dose reduced to 25% and the prednisone dose to 50%. The CyA dose was adjusted to maintain trough levels of 150-200 ng/ml. RESULTS: There was an 85% reduction in the dose of CyA. The average costs were 10.61 pounds sterling for CyA alone compared with pound 2.26 (pounds sterling) for the CyA-KZ combination, which represents an average savings of 8.35 pounds sterling (79%) per patient per day. The estimated savings during the study period was 999,930 pounds sterling. The patient and graft survival for patients receiving KZ was similar to patients on the South African Dialysis and Transplant Registry. Graft survival was significantly worse in black patients. CONCLUSION: The use of KZ with CyA in renal transplant recipients with stable allograft function results in a significant reduction in the dose of CyA and a significant cost savings, without compromising patient or graft survival. The regimen may be useful in countries with limited resources.

Withdrawal of cyclosporine in renal transplant recipients with acute tubular necrosis improves renal function.

In this study, patients with acute tubular necrosis (ATN) after renal transplantation were prospectively randomized to either conventional immunosuppression or withdrawal of cyclosporine and replacement with anti-thymocyte globulin (ATG). The patients treated with cyclosporine withdrawal and ATG had a significantly shorter duration of ATN (8.9 +/- 1.5 vs 10.8 +/- 1.4 days; P < 0.05) and better renal function (mean serum creatinine on day 5 postoperatively: 740 +/- 49 vs 918 +/- 73 micromol/l; P < 0.05). The incidence of acute rejection was lower in the patients with cyclosporine withdrawal and ATG. In conclusion, cyclosporine is toxic to the renal allograft with ATN, and withdrawal of cyclosporine shortens the duration of ATN and improves renal function.

Does rural follow-up of renal allografts give impaired graft survival?

In this study, we compared the patient and graft survival after renal transplantation in patients followed up in rural centers against those in a major transplant center. There was a greater proportion of patients having a living related donor transplant and having prolonged cold ischemic times in the group followed up in a rural centre. The patient and graft survival at 1, 3 and 5 years were similar for local and rural patients. We conclude that a centralized transplant unit with follow-up of patients in rural centers optimizes the use of highly skilled personnel.

Prolonged survival of baboon renal allografts using idarubicin-conjugated anti-CD4 monoclonal antibodies.

Tolerance to organ allografts in rodents and pigs can be easily achieved. However, tolerance induction in a large primate model has been more elusive. In this study, we have used an anti-CD4, murine monoclonal antibody as a carrier for the cytotoxic drug idarubicin (IDA) to delete or inactivate alloreactive T-cells responding to a renal allograft in a baboon transplant model. Fourteen Chacma baboons weighing between 15-25 kg received heterotopic renal allografts. Recipient and donor pairs were selected on the basis of ABO compatibility. Seven animals were given no immunosuppression and served as the control group. The remaining 7 animals received anti-CD4 IDA. The first 2 animals in this group received 2 mg IVI intraoperatively and three doses at 48-h intervals thereafter. The last 5 animals received a larger dose of 1 mg/kg, starting 24 h preoperatively and again on postoperative days 2 and 5. The untreated animals promptly rejected their allografts with a mean survival of 10 days. The survival of the 2 animals treated with 2 mg anti-CD4 IDA was 7 days each. However, the animals treated with 1 mg/kg anti-CD4 IDA survived 7, 18, 20, 40 and > 40 days. Peritransplant administration of anti-CD4 IDA prolonged renal allograft survival in a large primate model. This unique immunoconjugate has the potential of tolerance induction.

Ten years of liver transplantation at Groote Schuur Hospital.

INTRODUCTION: Liver transplantation has evolved from an experimental procedure to being the treatment of choice for many patients with end-stage liver disease, and is performed on a routine basis in most major centres throughout the world. However, certain situations peculiar to developing countries have a major impact on liver transplant programmes in these countries. We present the results of the liver transplant programme in Cape Town. PATIENTS AND METHODS: All patients undergoing orthotopic liver transplantation at Groote Schuur Hospital and Red Cross War Memorial Children's Hospital were included in this report. Standard surgical techniques were used for procuring the donor liver, the recipient hepatectomy and the subsequent implantation of the liver. All patients received standardised peri-operative management; in particular, the immunosuppressive protocol consisted of cyclosporin, steroids and azathioprine. Since October 1988, 83 patients have undergone 89 orthotopic liver transplants. There were 44 adults and 39 children, the age range being from 6 months to 56 years. The commonest indications for hepatic transplantation in adults included cryptogenic cirrhosis, auto-immune hepatitis and primary sclerosing cholangitis. In children biliary atresia was the commonest cause of liver failure. RESULTS: Of the 81 patients transplanted, 50 are alive and well with follow-up ranging from 2 months to 9.5 years. The cumulative graft survival rate was 72% at 1 year and 61% at 5 years. Six patients have undergone re-transplantation and 4 patients have had combined liver/kidney transplants. De novo hepatitis due to hepatitis B virus (HBV) has occurred in 8 patients following transplantation. Subsequent investigation has shown that 5 of the donors of these livers were hepatitis B core antibody (HBcAb)-positive, while information on the remaining 3 was not available. Tuberculosis (TB) has been a significant problem in 4 patients, with 2 deaths precipitated by anti-TB drug-induced hepatitis. Post-transplant lymphoproliferative disorder was also responsible for significant postoperative morbidity. CONCLUSION: Orthotopic liver transplantation has been established at Groote Schuur Hospital as the treatment of choice for selected patients with chronic end-stage liver disease. However, hepatitis B and TB appear to present a problem. The particularly high prevalence of HBV carrier status in our donor population may necessitate the use of living donors in the future.

A tale of two kidneys--how long can a kidney transplant wait?

This paper compares early graft function (EGF) of the first transplanted kidney (group 1) with the kidney transplanted second (group 2) in kidney pairs from the same cadaver donor. Thirty-one pairs of kidneys were harvested from cadaver donors between January 1997 and October 1998. Each pair was transplanted using a standard technique by the same team of surgeons, one after the other, as a result of limitations in theatre time and staff availability. Incidence of acute rejection (AR), acute tubular necrosis (ATN) and need for post-transplant dialysis was recorded for both groups, and was compared using the relevant statistical methods. Patients in both groups were well matched for age, gender and mode of dialysis pre-transplant. Human leucocyte antigen (HLA) matching and panel reactive antibody (PRA) status were similar in the two groups (p > 0.05). Cold ischaemia time (CIT) in the two groups was 14.1 +/- 5.7 and 19.2 +/- 6.9 h, respectively, the difference being statistically significant (p < 0.05). The incidence of AR was similar in the two groups. However, ATN (on renogram) was significantly more common in group 2 (p < 0.05; 12 patients versus 5 patients in group 1). All patients with ATN required post-transplant dialysis. Hospital stay was significantly prolonged in group 2 patients (p < 05; 20 +/- 10.6 versus 16.3 + 6.2 d for group 1). Even a relatively short increase in CIT can cause the second transplanted kidney of a pair to have a significantly higher incidence of ATN, resulting in need for dialysis and prolongation of hospital stay. Simultaneous transplantation, in areas lacking organ sharing networks, would not only improve EGF, but also improve long term graft survival. In addition, the reduced requirement for post-transplant dialysis and a shorter hospital stay would balance any increased demand on resources.

Renal transplantation from a living related donor with a retrocaval ureter--a note of caution.

In our study we describe a renal transplant from a living related donor who was found to have a retrocaval ureter. The retrocaval ureter is a rare congenital anomaly resulting from a defect in the embryological development of the ureter and the inferior vena cava (IVC). The compression of the ureter between the IVC and the vertebrae can result in progressive hydronephrosis. The non-dilated segment of the ureter was used for the uretero-neocystostomy. The patient presented with ureteric obstruction in the immediate post-transplant period, and at surgical exploration the ureteroneocystostomy was revised using the dilated portion of the ureter. We recommend that when transplanting a kidney with a retrocaval ureter, caution should be exercised in using the non-dilated portion of the ureter, since either the blood supply may be compromised or the peristalsis may be interrupted.

Parathyroid function after successful renal transplantation.

PURPOSE: The aim of this retrospective study was to assess parathyroid function after renal transplantation in patients with good renal function (creatinine < 133 mumol/l). METHODS AND MATERIALS: Of 1,628 patients on whom we performed renal transplantation, 210 have stable good renal function as defined above. Total calcium (Ca), creatinine, albumin and parathyroid hormone (PTH) values were obtained from patient records at varying intervals after transplantation, and in 91/210 patients pre-transplant values were available. Patients who had undergone parathyroidectomy before the transplant were excluded from the study. Follow-up ranged from 6 months to 24 years. RESULTS: These 210 patients were divided into 4 groups according to PTH and Ca levels. Group 1 consisted of 118 patients (56%) with normal Ca and PTH levels and group 2 of 69 patients (33%) with normal Ca but persistently high PTH levels, of whom 25 persistently have Ca levels in the high normal range. The reason for the inappropriate PTH levels is not obvious. In group 3 there were 18 patients (8%) with high Ca and PTH levels. They have disease requiring parathyroidectomy. Group 4 comprised 5 patients (3%) with low Ca and high PTH levels. In the 91 patients for whom pre-transplant PTH values were available, 16/46 patients with tertiary hyperparathyroidism (3 degrees HPT) have normalised after transplant, 12/46 patients have ongoing 3 degrees HPT post transplant, while 4/45 patients with less severe disease (secondary HPT) have developed 3 degrees HPT (P < 0.059). CONCLUSIONS: In 56% of patients with good renal function after transplant parathyroid function is normal. Thirty-three per cent have high PTH levels with normal Ca, but 36% of these are in the high normal range. Eight per cent have persistent 3 degrees HPT. Post-transplant parathyroid dysfunction correlates with the severity of pre-transplant disease.

Efficacy and tolerability of pantoprazole 40 mg versus 80 mg in patients with reflux oesophagitis.

BACKGROUND: Pantoprazole is a substituted benzimidazole which is a potent inhibitor of gastric acid secretion by its action upon H+, K+-ATPase. METHODS: Pantoprazole 40 mg and 80 mg were compared in a randomized double-blind study in 192 out-patients with stage II or III (Savary-Miller classification) reflux oesophagitis. Patients received either pantoprazole 40 mg (n = 97) or pantoprazole 80 mg (n = 95), once daily before breakfast for 4 weeks. Treatment was extended for a further 4 weeks if the oesophagitis had not healed. RESULTS: After 4 weeks complete healing of the reflux oesophagitis was seen in 78% of protocol-correct patients given pantoprazole 40 mg daily (n = 86), and in 72% in the 80 mg (n = 87) group. The cumulative healing rates after 8 weeks were 95 and 94%, respectively (P > 0.05, Cochran-Mantel-Haenszel), and time until healing of oesophagitis comparable in both groups. Differences between doses were also not significant in an intention-to-treat analysis. Both dosing schedules were well tolerated and the patients experienced remarkable symptom relief. No adverse event or changes in laboratory values of clinical significance could definitely be ascribed to the trial medication. CONCLUSION: The 40 mg pantoprazole dosage is comparable to 80 mg in reflux oesophagitis, both in efficacy and tolerability.

The prevalence of antibodies to the hepatitis A virus in Owambo children.

The prevalence of hepatitis A virus infection, in a population as well as the age at which it is usually acquired reflect the prevailing socio-economic conditions and standards of public hygiene. Infection occurs equally in both the sexes. Black Africans are known to have a high prevalence of hepatitis A virus infection and do acquire the infection early in life. This study documents the age-specific prevalence in Owambo children and confirms an equal sex distribution.

Hepatitis B virus carrier state in black children in Ovamboland: role of perinatal and horizontal infection.

Hepatitis B surface antigen (HBsAg) was detected in 17% of adult males and 11% of mothers in Ovamboland , South West Africa/Namibia. Hepatitis B e antigen (HBeAg) was present in 15% of HBsAg-positive mothers. Only 1% of children less than 6 months of age were HBsAg-positive, compared with 13% of children over the age of 1 year. 27% of mothers who were HBsAg-positive had HBsAg-positive children, whereas the corresponding figure for mothers who were HBsAg-negative was 6%. 63% of mothers who were positive for both HBsAg and HBeAg had HBsAg-positive children. 37% of HBsAg-positive children had HBsAg-positive mothers, compared with 8% of HBsAg-negative children. Later "horizontal" rather than neonatal maternal-infant transmission of the hepatitis B virus (HBV) seems to be the more important mode of spread of this infection in Ovambo children. The difference in the pattern of transmission of this virus between the Far East and Africa seems to centre mainly on the differences in the HBeAg status of the mothers in these two regions.