A retrospective analysis of outcomes and complications of living- and deceased-donor split-liver transplantation in Johannesburg, South Africa

Background. South African transplant centres are faced with significant challenges in meeting the need for liver transplantation, owing to the low and ever-decreasing number of deceased-donor organs. To increase organ utility, deceased-donor split-liver transplant (DDSLT) and living-donor liver transplant (LDLT) programmes were initiated in the Wits Transplant Unit. Objective. To evaluate outcomes of the LDLT and DDSLT programmes. Methods. A retrospective analysis of de-identified recipient and donor variables from all adult and paediatric DDSLTs and LDLTs conducted between 2013 and 2021 was performed. Comparison of categorical study variables between graft types was done with the χ2 test. Continuous variables were compared by means of the independent samples t-test. Cox proportional hazards regression was performed to examine the effect of graft type on recipient and graft survival. All comparisons were made unadjusted, and adjusted for recipient age, recipient ethnicity, donor sex, and graft-weight-to-recipient-weight ratio (GWRWR) (for the paediatric cohort); and for donor age and GWRWR (for the adult cohort). Results. A total of 181 paediatric and 48 adult liver transplants have been performed since the inception of the two programmes. Chronic liver failure, specifically intra- and extrahepatic cholestatic disease, was our main indication for liver transplantation in both cohorts. There were no significant differences between the DDSLTs and LDLTs in respect of pre- or post-discharge intervention, in-hospital mortality, length of stay, and recipient or graft survival within both the paediatric and adult groups. Our overall 1- and 3-year survival estimates (95% confidence intervals) were 77% (70% - 83%) and 71% (64% - 78%) for the paediatric cohort, and 77% (62% - 87%) and 66% (50% - 78%) for the adult cohort, respectively. Conclusion. The results of this study demonstrate comparable outcomes between DDSLT and LDLT, indicating that both methods are effective approaches to optimise organ utilisation for liver transplantation within our setting

Pregnancy after kidney and liver transplantation

Pregnancy in kidney and liver transplant recipients presents unique challenges and risks for both maternal and fetal health. This article examines the management of pregnancy in kidney and liver transplant recipients, focusing on pre-pregnancy counselling, trimester-specific care, the teratogenic effects of immunosuppressive drugs, and the role of the multidisciplinary team. While South African (SA) data on this topic are limited, the Transplant Pregnancy Registry International has provided valuable insights. Despite the increased risk of maternal and fetal complications, the overall risk of graft loss during pregnancy is low. Graft survival rates are comparable between pregnant and non- pregnant transplant recipients, except for pregnancies occurring within 1 year of transplantation. By addressing the complexities of managing pregnant women with kidney or liver transplants, this article underscores the importance of tailored care and the involvement of various medical specialists. It also explores the safety of and potential complications associated with specific immunosuppressive therapies during pregnancy. Further research is needed to enhance our understanding and optimise the management of these high-risk pregnancies in SA

ABO-incompatible liver transplantation – exploring utilitarian solutions to restricted access and organ shortages: A single-centre experience from Johannesburg, South Africa

Background. Liver transplantation is the definitive management for severe acute liver failure refractory to supportive management, and end- stage chronic liver failure. Owing to a shortage of deceased liver donors, South Africa requires innovative techniques to broaden the donor pool. Objectives. This study evaluated the outcomes of the Wits Transplant Unit ABO-incompatible liver transplant (ABOi-LT) programme. Methods. This retrospective record review compared all adult and paediatric patients receiving ABO-compatible (ABOc) and ABO-incompatible (ABOi) liver transplants from January 2014 to December 2021 with a minimum one-year follow-up. Primary outcomes were recipient and graft survival and secondary outcomes included vascular, enteric and biliary complications, relook surgery, acute cellular rejection (ACR) and lenghth of hospital stay. Cox proportional hazards regression was performed to examine the effect of ABO-compatibility group on recipient and graft survival. The relationship between the ABO-compatibility group and categorical outcomes was assessed by binomial regression. Results. During the study period, 532 liver transplants were performed; 44/532 (8%) were ABOi of which 14/44 (32%) were paediatric and 30/44 (68%) adult recipients. Within the pediatric group, the proportion of transplants performed for acute liver failure was significantly higher in the ABOi group (7/14; 50%) compared with the ABOc group (33/207; 16%) (p=0.005). Comparable recipient and graft survival estimates were noted: one-, three- and five-year recipient survival in the ABOi group was 77% (95% confidence interval (CI) 44 - 92), 58% (95% CI 17 - 84) and 58% (95% CI 17 - 84) respectively. There were significantly increased relative risks of relook surgery for the ABOi group compared with the ABOc group, both overall (relative risk (RR) 1.74; 95% CI 1.10 - 2.75) and at 90 days (RR 2.28; 95% CI 1.27 - 4.11); and also, for pre-discharge bloodstream infection (BSI), (RR 1.84; 95% CI 1.11 - 3.06). In adults, there were significantly more acute indications for liver transplantation in the ABOi (10/30; 33%) compared with the ABOc group (26/281; 9%) (p=0.0007) with the most common cause being drug or toxin ingestion (16/36; 44%). For the ABOi group, recipient survival estimates (95% CI) at 1, 3 and 5 years were 71% (50 - 84), 63% (41 - 78) and 58% (37 - 75) which, as noted with complication rates, were similar between ABO groups. Conclusion. This study confirms ABOi-LT as a feasible option to increase the liver donor pool in this organ-depleted setting as recipient survival and complication rates were similar between ABO-compatibility groups

Wits Transplant Unit Annual Report 2022: Adult and paediatric liver transplantation

In 2022, the Wits Transplant Unit performed 57 liver transplants: 33/57 adult (58%) and 24/57 paediatric (42%) recipients. At the beginning of 2022, 28 candidates were on the adult waitlist. Forty-six candidates were added to the waitlist during the year. Sixty-five percent of waitlisted candidate were transplanted. Adult candidates remained on the waitlist for longer than previous years, with 52% of them waitlisted for less than one year before undergoing liver transplantation. There was a decrease in adult pretransplant mortality to 9% in 2021 from 25% in 2020. The most common aetiology in waitlist candidates was alcoholic steatohepatitis (ASH)/non-alcoholic steatohepatitis (NASH) (36%) and in recipients cholestatic (primary sclerosing cholangitis (PSC) and primary biliary sclerosis (PBC)) (40%). Most adult recipients received a deceased donor graft (79%). Unadjusted recipient one- and three-year survivals were 75% (95% confidence interval (CI) 65 - 83) and 74% (95% CI 65 - 81), respectively. In the paediatric population, the most common aetiologies for both pretransplant candidates and transplant recipients remained cholestatic disease and acute liver failure. There was a decrease in paediatric pretransplant mortality from 27% in 2017 to 6% in 2021. Unlike the adult cohort, most paediatric recipients received a living donor graft (79%). Unadjusted one-year and three-year survival rates were 85% (95% CI 75 - 92) and 68% (95% CI 56 - 77), respectively.

Acute cellular rejection in adult liver transplant recipients in Johannesburg, South Africa

Background. Wits Donald Gordon Medical Centre (WDGMC) in Johannesburg, South Africa, established a liver transplant programme in 2004. Acute cellular rejection (ACR) of the transplanted liver is a serious complication because of the potential for graft loss. ACR is defined as allograft dysfunction secondary to predominantly T-cell-mediated injury to the graft, and has been reported in up to 50% of liver transplants worldwide. While the advent of tacrolimus-based immunosuppression reduces the incidence of ACR in liver transplant recipients, it remains a concern. Objectives. To review the incidence and risk factors for ACR, as well as the impact of ACR on graft survival in adult liver transplant recipients at WDGMC. Methods. This was a retrospective review of first-time adult liver transplants performed from 1 January 2014 to 31 December 2022. Data collected included donor and recipient sociodemographic and clinical characteristics; transplant surgical procedure details; postoperative surgical complications; overall post-transplant ACR incidence rates in the first 365 days; ACR incidence stratified as early (≤90 days) and late (>91 days - <365 days); diagnosis and treatment details of biopsy-proven ACR episodes, including steroid resistance; and graft survival. Results. Of 326 first-time adult liver transplants performed during the review period, 295 were eligible for inclusion. The post-transplant ACR incidence rates were 10.7% (early), 8.8% (late) and 20.3% overall (first 365 days). Corticosteroid resistance occurred in 19% of adult liver transplant recipients with biopsy-proven ACR. Risk factors for early ACR were younger recipient age, black ethnicity and male-donor- to-female-recipient sex discordance. A higher pre-transplant model for end-stage liver disease (MELD) score was a risk factor in late ACR. Younger recipient age, black ethnicity, female sex, acute liver failure, lower donor risk index scores and postoperative biliary complications were associated with increased risk for ACR in the first 365 days. ACR was not significantly associated with increased graft loss in this cohort. Conclusion. While the incidence of ACR was low in this cohort, identification of ACR risk factors and presence of steroid-resistant ACR indicate the need for personalised and context-specific immunosuppression

The ‘ins and outs’ of colonoscopy at Wits Donald Gordon Medical Centre, South Africa: A practice audit of the outpatient endoscopy unit

Background. In South Africa, there are no national guidelines for the conduct or quality assessment of colonoscopy, the gold standard for investigation and diagnosis of bowel pathology.Objectives. To describe the clinical profile of patients and evaluate the practice of colonoscopy using procedural quality indicators at the Wits Donald Gordon Medical Centre (WDGMC) outpatient endoscopy unit (OEU).Methods. We conducted a prospective, clinical practice audit of colonoscopies performed on adults (≥18 years of age). A total of 1 643 patients were included in the study and variables that were collected enabled the assessment of adequacy of bowel preparation, length of withdrawal time and calculation of caecal intubation rate (CIR), polyp detection rate (PDR) and adenoma detection rate (ADR). We stratified PDR and ADR by sex, age, population group, withdrawal time and bowel preparation. CIR, PDR and ADR estimates were compared between patient groups by the χ2 test; Fisher’s exact test was used for 2 × 2 tables. A p-value <0.05 was used. Benchmark recommendations by the American Society for Gastrointestinal Endoscopy (ASGE)/American College of Gastroenterology (ACG) Task Force on Colorectal Cancer (CRC) were used in this audit to assess individual endoscopist performance and that of the endoscopy unit as a whole.Results. The mean age of patients was 55.7 (standard deviation (SD) 14.4; range 18 - 91) years, ~60% were female, and the majority (75.5%) were white. Of the outpatients, 77.6% had adequate bowel preparation (ASGE/ACG benchmark ≥85%). The CIR was 97.0% overall, and screening colonoscopy was 96.3% (ASGE/ACG benchmark ≥90% overall and ≥95% for screening colonoscopies). The median withdrawal time for negative-result screening colonoscopies was 5.7 minutes (interquartile range (IQR) 4.2 - 9.3; range 1.1 - 20.6) (ASGE/ACG benchmark ≥ 6minutes), and PDR and ADR were 27.6% and 15.6%, respectively (ASGE/ACG benchmark ADR ≥25%). We demonstrated a 23.7% increase in PDR and 14.1% increase in ADR between scopes that had mean withdrawal times of ≥6 minutes and <6 minutes, respectively. Although the number of black Africans in the study was relatively small, our results showed that they have similar ADRs and PDRs to the white population group, contradicting popular belief.Conclusions. The WDGMC OEU performed reasonably well against the international guidelines, despite some inadequacy in bowel preparation and lower than recommended median withdrawal times on negative-result colonoscopy. Annual auditing of clinical practice and availability of these data in the public domain will become standard of care, making this audit a baseline for longitudinal observation, assessing the impact of interventions, and contributing to the development of local guidelines

Natural and Vaccine-Mediated Immunity to Salmonella Typhimurium is Impaired by the Helminth Nippostrongylus brasiliensis

The impact of exposure to multiple pathogens concurrently or consecutively on immune function is unclear. Here, immune responses induced by combinations of the bacterium Salmonella Typhimurium (STm) and the helminth Nippostrongylus brasiliensis (Nb), which causes a murine hookworm infection and an experimental porin protein vaccine against STm, were examined. Mice infected with both STm and Nb induced similar numbers of Th1 and Th2 lymphocytes compared with singly infected mice, as determined by flow cytometry, although lower levels of secreted Th2, but not Th1 cytokines were detected by ELISA after re-stimulation of splenocytes. Furthermore, the density of FoxP3+ T cells in the T zone of co-infected mice was lower compared to mice that only received Nb, but was greater than those that received STm. This reflected the intermediate levels of IL-10 detected from splenocytes. Co-infection compromised clearance of both pathogens, with worms still detectable in mice weeks after they were cleared in the control group. Despite altered control of bacterial and helminth colonization in co-infected mice, robust extrafollicular Th1 and Th2-reflecting immunoglobulin-switching profiles were detected, with IgG2a, IgG1 and IgE plasma cells all detected in parallel. Whilst extrafollicular antibody responses were maintained in the first weeks after co-infection, the GC response was less than that in mice infected with Nb only. Nb infection resulted in some abrogation of the longer-term development of anti-STm IgG responses. This suggested that prior Nb infection may modulate the induction of protective antibody responses to vaccination. To assess this we immunized mice with porins, which confer protection in an antibody-dependent manner, before challenging with STm. Mice that had resolved a Nb infection prior to immunization induced less anti-porin IgG and had compromised protection against infection. These findings demonstrate that co-infection can radically alter the development of protective immunity during natural infection and in response to immunization