Journal of Transplantation

Introduction. Histopathological assessment of liver biopsies is the current “gold standard” for diagnosing graft dysfunction after liver transplantation (LT), as graft dysfunction can have nonspecific clinical presentations and inconsistent patterns of liver biochemical dysfunction. Most commonly, post-LT, graft dysfunction within the first year, is due to acute T-cell mediated rejection (TCMR) which is characterised histologically by the degree of portal inflammation (PI), bile duct damage (BDD), and venous endothelial inflammation (VEI). This study aimed to establish the relationship between global assessment, which is the global grading of rejection using a “gestalt” approach, and the rejection activity index (RAI) of each component of TCMR as described in revised Banff 2016 guidelines. Methods. Liver biopsies (n = 90) taken from patients who underwent LT in 2015 and 2016 at the Australian National Liver Transplant Unit were identified from the electronic medical records. All biopsy slides were microscopically graded by at least two assessors independently using the revised 2016 Banff criteria. Data were analysed using IBM SPSS v21. A Fisher–Freeman–Halton test was performed to assess the correlation between the global assessment and the RAI scores for each TCMR biopsy. Results. Within the cohort, 60 (37%, n = 164) patients underwent at least 1 biopsy within 12 months after LT. The most common biopsy outcome (total n = 90) was acute TCMR (64, 71.1%). Global assessment of TCMR slides strongly positively correlated with PI ( value <0.001), BDD ( value <0.001), VEI ( value <0.001), and total RAI ( value <0.001). Liver biochemistry of patients with TCMR significantly improved within 4 to 6 weeks post-biopsy compared to the day of the biopsy. Conclusion. In acute TCMR, global assessment and total RAI are strongly correlated and can be used interchangeably to describe the severity of TCMR.

Background. Pericardial effusions are a known complication posthematopoietic stem cell transplant (HSCT), causing significant morbidity. We aimed to evaluate the risk factors associated with the development of high-grade effusions requiring interventions. Procedure. A retrospective chart review of all HSCT patients over a period of 7 years (2013–2019) in a single institution in the Northeastern United States is conducted. All patients who developed an effusion requiring intervention were included. Patient’s clinical characteristics were compared with all others transplanted during the same time period. Echocardiogram findings of the affected patients were compared to a case-control cohort of unaffected patients with similar age and diagnosis. Chi-square and paired t-tests were utilized to ascertain statistical differences between the groups. Results. A total of 15 patients out of 201 (7.5%) transplanted at our institution developed a moderate or large pericardial effusion requiring pericardiocentesis or a pericardial window. Of this cohort, 13 (87%) underwent a myeloablative preparative regimen, 13 (87%) had cyclophosphamide as part of their regimen, 13 (87%) had recent treatment for viral reactivation, 6 (40%) had an underlying hemoglobinopathy diagnosis, and only 4 (27%) had an active diagnosis of GVHD. A myeloablative preparative regimen had a higher rate of effusion requiring intervention, although it was not statistically significant, and concurrent GVHD was not predictive of effusion development. However, exposure to cyclophosphamide, recent treatment for viral reactivation, and a diagnosis of transplant-associated thrombotic microangiopathy (Ta-TMA) were highly associated with effusions. The latter was associated with increased mortality. The duration of pericardial effusion correlated with the pretransplant echocardiogram left ventricle end diastolic diameter z-score and apical 4-chamber left ventricular peak average strain measurement. Conclusions. Potential risk factors for pericardial effusions post-HSCT include a diagnosis of Ta-TMA, active viral infection, exposure to cyclophosphamide, and a higher left ventricle end diastolic diameter z-score. This information may help guide management for these patients, including identifying high-risk subjects, determining the frequency of echocardiograms, and determining specific echocardiogram measures to follow over time.

Background. Nonadherence to immunosuppression in liver transplant recipients (LTRs) leads to deterioration in health outcomes. Once-dailyextended-release tacrolimus (TAC-ER) may improve adherence when compared to twice-dailyimmediate-release tacrolimus (TAC-IR). Methods. We conducted a randomized controlled study to evaluate medication adherence, clinical efficacy, and safety of TAC-ER in stable LTR. All patients >18 years who underwent liver transplantation before 6 months were eligible. Patients were randomized 1 : 1 to continued TAC-IR or conversion to TAC-ER. The primary outcome was change in medication adherence from baseline to 9 months, assessed using BAASIS. Secondary outcomes were tacrolimus trough levels, safety, and quality of life. Results. Thirty-one patients were consented and randomized to either of the two groups: conversion to TAC-ER (n = 15) or continued TAC-IR (n = 16). Six patients in the TAC-ER group withdrew after randomization due to apprehension about switching medication (n = 2), unwillingness to travel (n = 2), and increased liver tests after conversion (n = 2, both were acute rejections despite therapeutic tacrolimus levels and were considered unrelated to TAC-ER). We compared the results of nine patients in the TAC-ER group that completed the study with those of sixteen in the TAC-IR group. At baseline, there was no difference in tacrolimus trough levels between groups. Improved adherence was observed in the TAC-ER group as 100% of patients reported at least one period of full adherence during the study period (100% vs. 62.6%, ). Tacrolimus trough levels and liver tests were comparable between groups throughout the study. There were no differences in eGFR, HbA1c, or QoL between the groups. Conclusion. TAC-ER improved medication adherence while maintaining comparable trough levels, liver function, and QoL as TAC-IR in LTR.

Background. The incidence of chronic liver disease is increasing in the Nepalese population. Liver transplantation (LT) is the best option for patients with end-stage liver disease (ESLD). Nepal’s first liver transplant was performed in 2016 in an international collaborative effort at Shahid Dharmabhakta National Transplant Centre (SDNTC), Bhaktapur, Nepal. We aim to report details of the first five patients who had undergone liver transplantation in SDNTC before the beginning of the COVID-19 outbreak in the history of transplantation in Nepal. Method. A descriptive analysis of the clinical data of five adult recipients of liver transplantation at SDNTC was done. We described the patient’s demographics, length of stay, and survival of all the first five patients who had undergone four living donor liver transplantations and one brain-dead donor liver transplantation in SDNTC before the beginning of the COVID-19 outbreak. Results. Recipients were between 36 and 63 years old. The recipients of the four live donor liver transplants (LDLT) and one brain-dead donor liver transplant (DDLT) had alcoholic liver disease and cryptogenic liver disease, leading to end-stage liver disease. The model for end-stage liver disease (MELD) scores ranged from 23 to 34. Out of five, four recipients and four donors are doing well and relishing the prospect of a normal life, while the recipient of a brain-dead donor liver transplant passed away due to postoperative primary graft failure. Conclusion. Despite the small number of liver transplants that have been done, the success of these has created confidence in a sustainable liver transplantation program in Nepal.

Background. There is an increasing demand for kidney retransplantation. Most studies report inferior outcomes compared to primary transplantation, consequently feeding an ethical dilemma in the context of chronic organ shortage. Objective. To assess variables influencing long-term graft survival after kidney retransplantation. Material and Methods. All patients transplanted at our center between 2000 and 2016 were analyzed retrospectively. Survival was estimated with the Kaplan–Meier method, and risk factors were identified using multiple Cox regression. Results. We performed 1,376 primary kidney transplantations and 222 retransplantations. The rate of retransplantation was 67.8% after the first graft loss, with a comparable 10-year graft survival compared to primary transplantation (67% vs. 64%, ) but an inferior graft survival thereafter (log-rank ). Independent risk factors for graft survival in retransplantation were age ≥ 50 years, time on dialysis ≥1 year, previous graft survival <2 years, ≥1 mild comorbidity in the Charlson–Deyo index, active smoking, and life-threatening complications (Clavien–Dindo grade IV) at first transplantation. Conclusion. Graft survival is comparable for first and second kidney transplantation within the first 10 years. Risk factors for poor outcomes after retransplantation are previous graft survival, dialysis time after graft failure, recipient age, comorbidities, and smoking. Patients with transplant failure should have access to retransplantation as early as possible.

Background. Persistent orthostatic hypotension (OH) is a lesser-known complication of lung transplantation (LTx). In this retrospective case series, we describe the clinical manifestations, complications, and treatment of persistent OH in 13 LTx recipients. Methods. We identified LTx recipients who underwent transplantation between March 1, 2018, and March 31, 2020, with persistent symptomatic OH and retrospectively queried the records for clinical information. Results. Thirteen patients were included in the analysis, 9 (69%) had underlying pulmonary fibrosis, and 12 (92%) were male. The median age, height, and body mass index at LTx were 68 years, 70 inches, and 27 kg/m², respectively. Six (46%) patients were deceased at the time of chart abstraction with a median (IQR) posttransplant survival of 12.6 months (6, 21); the 7 remaining living patients were a median of 19.6 months (18, 32) posttransplant. Signs and symptoms of OH developed a median of 60 (7, 75) days after transplant. Patients were treated with pharmacological agents and underwent extensive physical therapy. Most patients required inpatient rehabilitation (n = 10, 77%), and patients commonly developed comorbid conditions including weight loss, renal insufficiency with eGFR <50 (n = 13, 100%), gastroparesis (n = 7, 54%), and tachycardia-bradycardia syndrome (n = 2, 15%). Falls were common (n = 10, 77%). The incidence of OH in LTx recipients at our center during the study period was 5.6% (13/234). Conclusions. Persistent OH is a lesser-known complication of LTx that impacts posttransplant rehabilitation and may lead to comorbidities and shortened survival. In addition, most LTx recipients with OH at our center were tall, thin men with underlying pulmonary fibrosis, which may offer an opportunity to instate pretransplant OH screening of at-risk patients.