Living-Donor Liver Transplant in Oman: A Quantitative Cross-Sectional Study of Donors’ Experiences and Challenges

Background. In Oman, the first liver transplant was performed at the Royal Hospital (RH) in September 2017. Since then, thirteen cases have been operated on at the RH. All of these cases were living-donor liver transplants (LDLT), and the remaining cases were treated in India with a total of approximately 193 recipients. To provide an in-depth overview of donor experiences, challenges, and perceptions, a cross-sectional study was conducted. Methods. A cross-sectional study was conducted at one tertiary hospital in 2019. The survey was designed to collect data composed of closed and open-ended questions to reveal a thorough knowledge of the topic. Results. A total of 50 of 120 donors responded to the survey with male dominance in the sample (68%) and 64% were aged 28 to 38 years. 66% of the respondents came to know about the donation through hospital staff. Interestingly, respondents (n = 8/12) who reported that fear of operation is the cause that prevents people from donating are among the male gender, while more men believe that the main cause is lack of knowledge. 90% of the respondents felt satisfied after donation. More men reported ambiguous feelings before donation. Moreover, married donors reported ambiguous feelings before donation (p = 0.008). The younger age group reported anxiety and doubt as a challenge through their donation experience. Conclusion. This study revealed that donors have a positive feeling after donating as they have saved a life, as well as being empowered by family and community. The donors encourage individuals to donate a portion of their liver. Some crucial questions arose, such as anxiety before surgery, ambiguous feelings before surgery, and fatigue after surgery. These findings underscore the importance of a holistic approach that would enable donors to be well informed prior to surgery.

Natural Antibodies and Alloreactive T Cells Long after Kidney Transplantation

Background. The relationship between circulating effector memory T and B cells long after transplantation and their susceptibility to immunosuppression are unknown. To investigate the impact of antirejection therapy on T cell-B cell coordinated immune responses, we assessed IFN-γ-producing memory cells and natural antibodies (nAbs) that potentially bind to autoantigens on the graft. Methods. Plasma levels of IgG nAbs to malondialdehyde (MDA) were measured in 145 kidney transplant recipients at 5–7 years after transplantation. In 54 of these patients, the number of donor-reactive IFN-γ-producing cells was determined. 35/145 patients experienced rejection, 18 of which occurred within 1 year after transplantation. Results. The number of donor-reactive IFN-γ-producing cells and the levels of nAbs were comparable between rejectors and nonrejectors. The nAbs levels were positively correlated with the number of donor-reactive IFN-γ-producing cells (rs = 0.39, p = 0.004 ). The positive correlation was only observed in rejectors (rs = 0.53, p = 0.003 ; nonrejectors: rs = 0.24, p = 0.23 ). Moreover, we observed that intravenous immune globulin treatment affected the level of nAbs and this effect was found in patients who experienced a late ca-ABMR compared to nonrejectors ( p = 0.008 ). Conclusion. The positive correlation found between alloreactive T cells and nAbs in rejectors suggests an intricate role for both components of the immune response in the rejection process. Treatment with intravenous immune globulin impacted nAbs.

Waitlist Mortality and Posttransplant Outcomes in African Americans with Autoimmune Liver Diseases

Background. Liver transplantation is indicated in end-stage liver disease due to autoimmune diseases. The liver allocation system can be affected by disparities such as decreased liver transplant referrals for racial minorities, especially African Americans that negatively impact the pre- and posttransplant outcomes. Aim. To determine differences in waitlist survival and posttransplant graft survival rates between African American and Caucasian patients with autoimmune liver diseases. Study. The United Network for Organ Sharing database was used to identify all patients with autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis who underwent liver transplant from 1988 to 2019. We compared waitlist survival and posttransplant graft survival between Caucasians and African Americans using Kaplan–Meier curves and Cox regression models. We also evaluated the cumulative incidence of death or delisting for deterioration and posttransplant incidence of death and retransplantation using competing risk analysis. Results. African Americans were more likely to be removed from the waitlist for death or clinical deterioration (subdistribution hazard ratio (SHR) 1.26, 95% CI 1–1.58, P = 0.046 ) using competing risk analysis. On multivariate Cox regression analysis, there was no difference in posttransplant graft survival among the two groups (hazard ratio (HR) 1.10, 95% CI 0.98–1.23, P = 0.081 ). Conclusions. Despite the current efforts to reduce racial disparities, we found that African Americans are more likely to die on the waitlist for liver transplant and are less likely to be transplanted, with no differences in graft survival rates. The persistence of healthcare disparities continues to negatively impact African Americans.

Is Bigger Better? Living Donor Kidney Volume as Measured by the Donor CT Angiogram in Predicting Donor and Recipient eGFR after Living Donor Kidney Transplantation

Background. The role of kidney volume measurement in predicting the donor and recipient kidney function is not clear. Methods. We measured kidney volume bilaterally in living kidney donors using CT angiography and assessed the association with the donor remaining kidney and recipient kidney (donated kidney) function at 1 year after kidney transplantation. Donor volume was categorized into tertiles based on lowest, middle, and highest volume. Results. There were 166 living donor and recipient pairs. The mean donor age was 44.8 years (SD ± 10.8), and donor mean BMI was 25.5 (SD ± 2.9). The recipients of living donor kidneys were 64% male and had a mean age of 43.5 years (SD ± 13.3). Six percent of patients experienced an episode of cellular rejection and were maintained on dialysis for a mean of 18 months (13–32) prior to transplant. Kidney volume was divided into tertiles based on lowest, middle, and highest volume. Kidney volume median (range) in tertiles 1, 2, and 3 was 124 (89–135 ml), 155 (136–164 ml), and 184 (165–240 ml) with donor eGFR ml/min (adjusted for body surface area expressed as ml/min/1.73 m2) at the time of donation in each tertile, 109 (93–129), 110 (92–132), and 101 ml/min (84–117). The median (IQR) eGFR in tertiles 1 to 3 in kidney recipients at 1 year after donation was 54 (44–67), 62 (50–75), and 63 ml/min (58–79), respectively. The median (IQR) eGFR in tertiles 1 to 3 in the remaining kidney of donors at 1 year after donation was 59 (53–66), 65 (57–72), and 65 ml/min (56–73), respectively. Conclusion. Bigger kidney volume was associated with better eGFR at 1 year after transplant in the recipient and marginally in the donor remaining kidney.

The Impact of Timing of Stent Removal on the Incidence of UTI, Recurrence, Symptomatology, Resistance, and Hospitalization in Renal Transplant Recipients

Purpose. To evaluate the impact of early (<3 weeks) versus late (>3 weeks) urinary stent removal on urinary tract infections (UTIs) post renal transplantation. Methods. A retrospective study was performed including all adult renal transplants who were transplanted between January 2017 and May 2020 with a minimum of 6-month follow-up at King Abdulaziz Medical City, Riyadh, Saudi Arabia. Results. A total of 279 kidney recipients included in the study were stratified into 114 in the early stent removal group (ESR) and 165 in the late stent removal group (LSR). Mean age was 43.4 ± 15.8; women: n: 114, 40.90%; and deceased donor transplant: n: 55, 19.70%. Mean stent removal time was 35.3 ± 28.0 days posttransplant (14.1 ± 4.6 days in the ESR versus 49.9 ± 28.1 days in LSR, p < 0.001 ). Seventy-four UTIs were diagnosed while the stents were in vivo or up to two weeks after the stent removal “UTIs related to the stent” (n = 20, 17.5% in ESR versus n = 54, 32.7% in LSR; p = 0.006 ). By six months after transplantation, there were 97 UTIs (n = 36, 31.6% UTIs in ESR versus n = 61, 37% in LSR; p = 0.373 ). Compared with UTIs diagnosed after stent removal, UTIs diagnosed while the stent was still in vivo tended to be complicated (17.9% versus 4.9%, p : 0.019), recurrent (66.1% versus 46.3%; p : 0.063), associated with bacteremia (10.7% versus 0%; p : 0.019), and requiring hospitalization (61% versus 24%, p : 0.024). Early stent removal decreased the need for expedited stent removal due to UTI reasons (rate of UTIs before stent removal) (n = 11, 9% in the early group versus n = 45, 27% in the late group; p = 0.001 ). The effect on the rate of multidrug-resistant organisms (MDRO) was less clear (33% versus 47%, p : 0.205). Early stent removal was associated with a statistically significant reduction in the incidence of UTIs related to the stent (HR = 0.505, 95% CI: 0.302-0.844, p = 0.009 ) without increasing the incidence of urological complications. Removing the stent before 21 days posttransplantation decreased UTIs related to stent (aOR: 0.403, CI: 0.218-0.744). Removing the stent before 14 days may even further decrease the risk of UTIs (aOR: 0.311, CI: 0.035- 2.726). Conclusion. Early ureteric stent removal defined as less than 21 days post renal transplantation reduced the incidence of UTIs related to stent without increasing the incidence of urological complications. UTIs occurring while the ureteric stent still in vivo were notably associated with bacteremia and hospitalization. A randomized trial will be required to further determine the best timing for stent removal.

The Living-Related Kidney Transplant Program in Brunei Darussalam: Lessons Learnt from a Nascent National Program in a Small, Muslim, and Asian Country

Brunei Darussalam commenced its living-related renal transplant program in 2013, with subsequent attainment of independent local capacity and proficiency in 2019. The preliminary outcome from the program has already begun to shape the national nephrology landscape with a 36% increment in transplant rate and mitigation of commercialized transplantations. The blueprint for the program was first laid out in 2010 and thereupon executed in four phases. The first phase involved the gathering of evidence to support the establishment of the national program, through researches investigating feasibility, public opinion, quality of life, graft survival, and cost-effectiveness. The second phase focused on laying the foundation of the program through grooming of local expertise, implementation of legal-ethical frameworks, religious legitimization, and propagation of awareness. The third phase worked on facilitating experiential exposure and strengthening local infrastructure through the upgrading of facilities and the introduction of subsidiary services. The fourth phase was implemented in Brunei in 2013 when foreign personnel worked together with the local team to perform the transplants. Between 2013 and 2019, ten kidney transplants were performed, with two being done in 2018 and three in 2019. We hope to inspire other similar countries to develop their own self-sustainable and independent local program.

Treatment of Hepatitis C Post-Liver Transplantation Could Mitigate Discard Rates of Hepatitis C-Positive Deceased Donor Livers and Expand the Donor Pool

Background. Prior to 2014, treatment for hepatitis C was limited. However, the subsequent introduction of direct acting antiviral medications (DAA) against hepatitis C led to improvements in morbidity and better medication tolerance. DAA therapy allowed for an increase in treatment rates of hepatitis C in patients on the liver transplant waiting list. With the popularization of DAA, there became a growing concern about the utility of hepatitis C-positive (HCV+) deceased liver donors, especially after treating HCV+ potential recipients on the transplant waiting list. Methods. This is a retrospective, observational study using Mid-America Transplant Services (MTS) database from 2008 to 2017. Comparison was made before the widespread use of DAAs 2008–2013 (pre-DAA) against their common practice use 2014–2017 (post-DAA). All deceased liver donors with HCV antibody or nucleic acid positive results were evaluated. Results. Between 2008 and 2017, 96 deceased liver donors were positive for HCV. In the pre-DAA era, 47 deceased liver donors were positive for HCV, of which 32 (68.1%) were transplanted and 15 (31.9%) were discarded. In the post-DAA era, a total of 49 HCV+ organs were identified, out of which 43 (87.8%) livers were transplanted and 6 (12.2%) were discarded. Discard rate was significantly higher in the pre-DAA population (31.9% vs. 12.2%, p = 0.026). Secondary analysis showed a distinct trend towards increased regional sharing and utilization of HCV+ donors. Conclusion. In order to reduce discard rates of HCV+ patients, our data suggest that transplant centers could potentially delay HCV treatment in patients on the transplant waitlist.

Reversibility of Frailty after Lung Transplantation

Background. Frailty contributes to increased morbidity and mortality in patients referred for and undergoing lung transplantation (LTX). The study aim was to determine if frailty is reversible after LTX in those classified as frail at LTX evaluation. Methods. Consecutive LTX recipients were included. All patients underwent modified physical frailty assessment during LTX evaluation. For patients assessed as frail, frailty was reassessed on completion of the post-LTX rehabilitation program. Frailty was defined by the presence of ≥ 3 domains of the modified Fried Frailty Phenotype (mFFP). Results. We performed 166 lung transplants (frail patients, n = 27, 16%). Eighteen of the 27 frail patients have undergone frailty reassessment. Eight frail patients died, and one interstate recipient did not return for reassessment. In the 18 (66%) patients reassessed, there was an overall reduction in their frailty score post-LTX ((3.4 ± 0.6 to 1.0 ± 0.7), p<0.001) with 17/18 (94%) no longer classified as frail. Improvements were seen in the following frailty domains: exhaustion, mobility, appetite, and activity. Handgrip strength did not improve posttransplant. Conclusions. Physical frailty was largely reversible following LTX, underscoring the importance of considering frailty a dynamic, not a fixed, entity. Further work is needed to identify those patients whose frailty is modifiable and establish specific interventions to improve frailty.

Sirtuin 1: A Dilemma in Transplantation

Sirtuin 1, a member of sirtuin family of histone deacetylase enzymes, has been implicated in a variety of physiologic and pathologic events, including energy metabolism, cell survival, and age-related alterations. In view of the anti-inflammatory properties of sirtuin 1 along with its protective role in ischemia reperfusion injury, it might be considered as contributing to the promotion of transplantation outcome. However, the potential ability of sirtuin 1 to induce malignancies raises some concerns about its overexpression in clinic. Moreover, despite the findings of sirtuin 1 implication in thymic tolerance induction and T regulatory (Treg) cells survival, there is also evidence for its involvement in Treg suppression and in T helper 17 cells differentiation. The identification of sirtuin 1 natural and synthetic activators leads to the proposal of sirtuin 1 as an eligible target for clinical interventions in transplantation. All positive and negative consequences of sirtuin 1 overactivation/overexpression in the allograft should therefore be studied thoroughly. Herein, we summarize previous findings concerning direct and indirect influences of sirtuin 1 manipulation on transplantation.

Pretransplant Donor-Specific Anti-HLA Antibodies and the Risk for Rejection-Related Graft Failure of Kidney Allografts

Background. The presence of donor-specific antibodies (DSAs) against HLA before kidney transplantation has been variably associated with decreased long-term graft survival. Data on the relation of pretransplant DSA with rejection and cause of graft failure in recipients of donor kidneys are scarce. Methods. Patients transplanted between 1995 and 2005 were included and followed until 2016. Donor-specific antibodies before transplantation were determined retrospectively. For cause, renal transplant biopsies were reviewed. Results. Pretransplant DSAs were found in 160 cases on a total of 734 transplantations (21.8%). In 80.5% of graft failures, a diagnostic renal biopsy was performed. The presence of pretransplant DSA (DSApos) increased the risk of graft failure within the first 3 months after transplantation (5.2% vs. 9.4%) because of rejection with intragraft thrombosis (p<0.01). One year after transplantation, DSApos recipients had an increased hazard for antibody-mediated rejection at 10 years (9% DSAneg vs. 15% DSApos, p=0.01) with significant decreased graft survival at 10 years (79% DSAneg vs. 69% DSApos, p=0.02). This could largely contribute to an increased graft loss because of antibody-mediated rejection in the DSApos group. The incidence and graft loss because of T cell-mediated rejection was not affected by the presence of pretransplant DSA. Conclusions. Pretransplant DSAs are a risk factor for early graft loss and increase the incidence for humoral rejection and graft loss but do not affect the risk for T cell-mediated rejection.