Risk Of Acute Cellular Rejection Research Articles

Novel dimensionality reduction method, Taelcore, enhances lung transplantation risk prediction

In this work, we present a new approach to predict the risk of acute cellular rejection (ACR) after lung transplantation by using machine learning algorithms, such as Multilayer Perceptron (MLP) or Autoencoder (AE), and combining them with topological data analysis (TDA) tools. Our proposed method, named topological autoencoder with best linear combination for optimal reduction of embeddings (Taelcore), effectively reduces the dimensionality of high-dimensional datasets and yields better results compared to other models. We validate the effectiveness of Taelcore in reducing the prediction error rate on four datasets. Furthermore, we demonstrate that Taelcore’s topological improvements have a positive effect on the majority of the machine learning algorithms used. By providing a new way to diagnose patients and detect complications early, this work contributes to improved clinical outcomes in lung transplantation.

Microcirculatory Disease in Patients after Heart Transplantation.

Although the treatment and prognosis of patients after heart transplantation have significantly improved, late graft dysfunction remains a critical problem. Two main subtypes of late graft dysfunction are currently described: acute allograft rejection and cardiac allograft vasculopathy, and microvascular dysfunction appears to be the first stage of both. Studies revealed that coronary microcirculation dysfunction, assessed by invasive methods in the early post-transplant period, correlates with a higher risk of late graft dysfunction and death during long-term follow-up. The index of microcirculatory resistance, measured early after heart transplantation, might identify the patients at higher risk of acute cellular rejection and major adverse cardiovascular events. It may also allow optimization and enhancement of post-transplantation management. Moreover, cardiac allograft vasculopathy is an independent prognostic factor for transplant rejection and survival rate. The studies showed that the index of microcirculatory resistance correlates with anatomic changes and reflects the deteriorating physiology of the epicardial arteries. In conclusion, invasive assessment of the coronary microcirculation, including the measurement of the microcirculatory resistance index, is a promising approach to predict graft dysfunction, especially the acute allograft rejection subtype, during the first year after heart transplantation. However, further advanced studies are needed to fully grasp the importance of microcirculatory dysfunction in patients after heart transplantation.

MTOR Inhibition Impairs the Activation and Function of Belatacept-Resistant CD4+CD57+ T Cells In Vivo and In Vitro.

Calcineurin inhibitors have improved graft survival in solid-organ transplantation but their use is limited by toxicity, requiring a switch to another immunosuppressor in some cases. Belatacept is one option that has been shown to improve graft and patient survival despite being associated with a higher risk of acute cellular rejection. This risk of acute cellular rejection is correlated with the presence of belatacept-resistant T cells. We performed a transcriptomic analysis of in vitro-activated cells to identify pathways affected by belatacept in belatacept-sensitive cells (CD4+CD57-) but not in belatacept-resistant CD4+CD57+ T cells. mTOR was significantly downregulated in belatacept-sensitive but not belatacept-resistant T cells. The inhibition of mTOR strongly decreases the activation and cytotoxicity of CD4+CD57+ cells. In humans, the use of a combination of mTOR inhibitor and belatacept prevents graft rejection and decreases the expression of activation markers on CD4 and CD8 T cells. mTOR inhibition decreases the functioning of belatacept-resistant CD4+CD57+ T cells in vitro and in vivo. It could potentially be used in association with belatacept to prevent acute cellular rejection in cases of calcineurin intolerance.

Personalized risk predictor for acute cellular rejection in lung transplant using soluble CD31

We evaluated the contribution of artificial intelligence in predicting the risk of acute cellular rejection (ACR) using early plasma levels of soluble CD31 (sCD31) in combination with recipient haematosis, which was measured by the ratio of arterial oxygen partial pressure to fractional oxygen inspired (PaO2/FiO2) and respiratory SOFA (Sequential Organ Failure Assessment) within 3 days of lung transplantation (LTx). CD31 is expressed on endothelial cells, leukocytes and platelets and acts as a “peace-maker” at the blood/vessel interface. Upon nonspecific activation, CD31 can be cleaved, released, and detected in the plasma (sCD31). The study included 40 lung transplant recipients, seven (17.5%) of whom experienced ACR. We modelled the plasma levels of sCD31 as a nonlinear dependent variable of the PaO2/FiO2 and respiratory SOFA over time using multivariate and multimodal models. A deep convolutional network classified the time series models of each individual associated with the risk of ACR to each individual in the cohort.

Presence of CD163+ macrophages in DCD kidneys with high DGF reduces the risk for acute cellular rejection in 6 months after kidney transplantation

Acute cellular rejection (ACR) occurs in 10% of renal allograft recipients and is characterized by leukocyte infiltration as observed in needle biopsies. ACR onset is subject to several risk factors, including delayed graft function (DGF). As the impact of DGF on the etiology of ACR remains unclear, this study analyzed the association between presence of leukocyte subsets and ACR onset, in DCD kidney biopsies with extensive DGF following transplantation. Immunohistochemical analysis of protocol biopsies taken 10 days after kidney transplantation revealed that patients with high levels of renal CD163+ macrophages have a decreased risk (OR = 0.021, P = 0.008) for ACR in the first 6 months after transplantation. In pre-transplant biopsies of a comparable DCD cohort, with >80% DGF, presence of donor CD163+ macrophages showed no effect on ACR risk. Therefore, leukocyte infiltrate present during the inflammatory response at the time of DGF may contain anti-inflammatory macrophages that exert a protective effect against ACR development.

Validation of donor fraction cell-free DNA with biopsy-proven cardiac allograft rejection in children and adults

ObjectivesDonor-specific cell-free DNA shows promise as a noninvasive marker for allograft rejection, but as yet has not been validated in both adult and pediatric recipients. The study objective was to validate donor fraction cell-free DNA as a noninvasive test to assess for risk of acute cellular rejection and antibody-mediated rejection after heart transplantation in pediatric and adult recipients. MethodsPediatric and adult heart transplant recipients were enrolled from 7 participating sites and followed for 12 months or more with plasma samples collected immediately before all endomyocardial biopsies. Donor fraction cell-free DNA was extracted, and quantitative genotyping was performed. Blinded donor fraction cell-free DNA and clinical data were analyzed and compared with a previously determined threshold of 0.14%. Sensitivity, specificity, negative predictive value, positive predictive value, and receiver operating characteristic curves were calculated. ResultsA total of 987 samples from 144 subjects were collected. After applying predefined clinical and technical exclusions, 745 samples from 130 subjects produced 54 rejection samples associated with the composite outcome of acute cellular rejection grade 2R or greater and pathologic antibody-mediated rejection 2 or greater and 323 healthy samples. For all participants, donor fraction cell-free DNA at a threshold of 0.14% had a sensitivity of 67%, a specificity of 79%, a positive predictive value of 34%, and a negative predictive value of 94% with an area under the curve of 0.78 for detecting rejection. When analyzed independently, these results held true for both pediatric and adult cohorts at the same threshold of 0.14% (negative predictive value 92% and 95%, respectively). ConclusionsDonor fraction cell-free DNA at a threshold of 0.14% can be used to assess for risk of rejection after heart transplantation in both pediatric and adult patients with excellent negative predictive value.

Temporal trends and current use of de novo belatacept in kidney transplant recipients in the United States.

The adoption of de novo belatacept in kidney transplant (kTx) recipients was hampered by an increased risk of acute cellular rejection (ACR) with variation in adopted belatacept based immunosuppressive therapies across centers. We used data from the Scientific Registry of Transplant Recipients (SRTR) to evaluate the temporal trends in belatacept use and describe the associated induction and maintenance regimens in US adult kTx recipients transplanted between June 2011 and December 2018. The number of patients receiving de novo-belatacept based immunosuppressive therapy increased from .74% in 2011 to 3.11% in 2016. In 2016, 66/207 centers used de novo belatacept-based regimen with 3.03% using it in over 50% of their patients. The use of T-cell depleting agents increased with time. Since 2012, the rate of calcineurin inhibitor (CNI) use in combination with belatacept remained stable around 50% and ∼30% remained under belatacept/CNI combination at 1-year post-transplantation. The adoption of belatacept as de novo immunosuppressive regimen has been slow and its use remains low in the United States. Various regimens have been used to modulate the risk of ACR. Further studies evaluating the long-term outcomes of these regimens and assessing their safety especially with regard to the risk of infection are needed.

Abstract 11935: The Index of Microcirculatory Resistance to Predict Subsequent Acute Cellular Rejection and Cardiac Events After Heart Transplantation

Introduction: Single center data suggest that the index of microcirculatory resistance (IMR) measured early after heart transplantation predicts subsequent acute cellular rejection. Hypothesis: To validate whether IMR measured early after transplantation can predict subsequent acute cellular rejection and long-term outcome in a large multicenter cohort. Methods: From 5 international heart transplantation cohorts, 237 patients who underwent IMR measurement early after transplantation were enrolled. The primary outcome was biopsy-proven acute cellular rejection of grade 2 or 3 within 1 year after transplantation. A key secondary outcome was major adverse cardiac events (MACE, the composite of death, re-transplantation, myocardial infarction, stroke, graft dysfunction, and readmission due to a cardiac cause) at 10 years. Results: IMR was measured at a median of 7 weeks (interquartile range: 3 to 10 weeks) post-transplantation. Patients with acute cellular rejection grade 2 or 3 at the time of IMR assessment were excluded. At 1 year, the incidence of acute cellular rejection was 14.0%. IMR was associated proportionally with the risk of acute cellular rejection (per increase of 1-unit IMR; adjusted hazard ratio [aHR], 1.04; 95% confidence interval [CI], 1.01-1.06; P=0.002). The incidence of acute cellular rejection in patients with IMR ≥ 18 was 23.8%, while the incidence of acute cellular rejection in those with IMR < 18 was 5.5% (aHR, 4.09; 95% CI, 1.67-10.0; P=0.002). At 10 years, MACE occurred in 86 (36.3%) patients. IMR was significantly associated with the risk of MACE (per increase of 1-unit IMR; aHR, 1.03; 95% CI, 1.01-1.05; P=0.002). Conclusions: IMR measured early after heart transplantation is associated with subsequent acute cellular rejection at 1 year and clinical events at 10 years. Early IMR measurement after transplantation identifies patients at higher risk and may guide personalized post-transplantation management.

Coronary Microcirculatory Dysfunction and Acute Cellular Rejection After Heart Transplantation.

Acute cellular rejection is a major determinant of mortality and retransplantation after heart transplantation. We sought to evaluate the prognostic implications of coronary microcirculatory dysfunction assessed by index of microcirculatory resistance (IMR) for the risk of acute cellular rejection after heart transplantation. The present study prospectively enrolled 154 heart transplant recipients who underwent scheduled coronary angiography and invasive coronary physiological assessment 1 month after transplantation. IMR is microcirculatory resistance under maximal hyperemia. By measuring hyperemic mean transit time using 3 injections (4 mL each) of room-temperature saline under maximal hyperemia, IMR was calculated as hyperemic distal coronary pressure×hyperemic mean transit time. The primary end point was biopsy-proven acute cellular rejection of grade ≥2R during 2 years of follow-up after transplantation and was compared by using multivariable Cox proportional hazards regression according to IMR. The incremental prognostic value of IMR, in addition to the model with clinical factors, was evaluated by comparison of C-index, net reclassification index, and integrated discrimination index. The mean age of recipients was 51.2±13.1 years (81.2% male), and the cumulative incidence of acute cellular rejection was 19.0% at 2 years. Patients with acute cellular rejection had significantly higher IMR values at 1 month than those without acute cellular rejection (23.1±8.6 versus 16.8±11.1, P=0.002). IMR was significantly associated with the risk of acute cellular rejection (per 5-U increase: adjusted hazard ratio, 1.18 [95% CI, 1.04-1.34], P=0.011) and the optimal cutoff value of IMR to predict acute cellular rejection was 15. Patients with IMR≥15 showed significantly higher risk of acute cellular rejection than those with IMR<15 (34.4% versus 3.8%; adjusted hazard ratio, 15.3 [95% CI 3.6-65.7], P<0.001). Addition of IMR to clinical variables showed significantly higher discriminant and reclassification ability for risk of acute cellular rejection (C-index 0.87 versus 0.74, P<0.001; net reclassification index 1.05, P<0.001; integrated discrimination index 0.20, P<0.001). Coronary microcirculatory dysfunction assessed by IMR measured early after heart transplantation showed significant association with the risk of acute cellular rejection. In addition to surveillance endomyocardial biopsy, early stratification using IMR could be a clinically useful tool to identify patients at higher risk of future acute cellular rejection after heart transplantation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02798731.

Effect of Mycophenolate Mofetil Dosing on 6-month Risk of Acute Cellular Rejection, Leukopenia and CMV Viremia in Heart Transplant

<h3>Purpose</h3> Mycophenolate mofetil (MMF) is a cornerstone of heart transplant (HT) therapy. MMF dose is associated with leukopenia and infections (eg CMV). Despite widespread use, the optimal MMF dose to balance risk of rejection with leukopenia and infection is unknown. Our center recently transitioned from a high-dose (HD) 3g/day to low-dose (LD) 2g/day MMF protocol. We tested whether LD-MMF is associated with: i) lower rates of leukopenia and CMV, and ii) comparable rates/severity of acute cellular rejection (ACR) at 6-months after HT. <h3>Methods</h3> 108 pts who received HT between 6/16 to 8/20 were included. Pts were categorized based on LD- vs HD-MMF. ACR was defined according to ISHLT criteria. A total rejection score (TRS) was calculated as follows: 0R=0, 1R=1, 2R=2, 3R=3 by dividing summed scores by total number of biopsies during study period. Leukopenia = WBC<4.0x10⁹/L. Between-group differences in freedom from ACR, leukopenia and CMV at 6-months were evaluated by KM method. Adjusted Hazard Ratios (HRs) were calculated from Cox proportional models. <h3>Results</h3> Baseline characteristics of HD- (n=71) vs LD-MMF (n=37) pts were similar including WBC and CMV match status; 80% vs 86% of pts were discharged at target doses. 59 ACR, 71 leukopenia and 10 CMV events occurred at 6-months. Freedom from first ACR, leukopenia and CMV in HD- vs L`D-MMF are shown in Fig 1a-c. Total ACR events in HD- vs LD- MMF group were 50/722 (6.9%) biopsies in 71 pts vs 9/272 (3.3%) biopsies in 37 pts. However, ACR events in HD-MMF group were less likely to be high grade (≥2R): 12% vs 55% (<i>p</i>=.002). TRS did not differ between groups: .075±.12 vs .05±.11, <i>p</i>=.08. After multivariable adjustments, HD-MMF was associated with higher risk of any ACR (HR=2.23, <i>p=</i>.043) and higher risk of leukopenia (HR=1.71 <i>p</i>=.049) (Fig 1d). <h3>Conclusion</h3> LD-MMF was associated with less leukopenia. However this came at the cost of more clinical significant ≥2R rejections. Further studies are warranted to address the long-term implications of these findings.

Long-Term Infectious and Noninfectious Outcomes of Monthly Alemtuzumab as a Calcineurin Inhibitor- and Steroid-Free Regimen for Pancreas Transplant Recipients.

Multiple doses of alemtuzumab for immunosuppressive therapy of patients with hematologic malignancies and hematopoietic stem cell transplant have been associated with a high rate of infection. In transplantation, limited alemtuzumab dosing has been successfully used as induction immunosuppression. The effect of multiple doses of alemtuzumab, used as maintenance therapy to minimize steroid and/or calcineurin inhibitor toxicity in solid organ transplant recipients, is unknown. We evaluated the infectious and noninfectious outcomes of 179 pancreas transplant recipients treated with alemtuzumab for induction and maintenance therapy (extended alemtuzumab exposure (EAE)) from 2/28/2003 through 8/31/2005, compared with 159 pancreas transplant recipients with standard induction and maintenance (SIM) therapy performed before (1/1/2002 until 12/31/2002) and after (1/1/2006 until 12/31/2006) the implementation of EAE. EAE was associated with higher risk of overall infections (hazard ratio (HR) 1.33 (1.06–1.66), P=0.01), bacterial infections (HR 1.33 (1.05–1.67), P=0.02), fungal infections (HR 1.86 (1.28–2.71), P < 0.01), and cytomegalovirus infections (HR 2.29 (1.39–3.77), P < 0.01). In addition, EAE was associated with higher risk of acute cellular rejection (HR 2.09 (1.46–2.99), P < 0.01). In conclusion, while a limited alemtuzumab dosing is safe and effective for induction therapy in pancreas transplantation, EAE combined with steroid and calcineurin minimization is associated with a high risk of infectious complications and acute cellular rejection.

Analytical Validation of HEARTBiT: A Blood-Based Multiplex Gene Expression Profiling Assay for Exclusionary Diagnosis of Acute Cellular Rejection in Heart Transplant Patients.

HEARTBiT is a whole blood-based gene profiling assay using the nucleic acid counting NanoString technology for the exclusionary diagnosis of acute cellular rejection in heart transplant patients. The HEARTBiT score measures the risk of acute cellular rejection in the first year following heart transplant, distinguishing patients with stable grafts from those at risk for acute cellular rejection. Here, we provide the analytical performance characteristics of the HEARTBiT assay and the results on pilot clinical validation. We used purified RNA collected from PAXgene blood samples to evaluate the characteristics of a 12-gene panel HEARTBiT assay, for its linearity range, quantitative bias, precision, and reproducibility. These parameters were estimated either from serial dilutions of individual samples or from repeated runs on pooled samples. We found that all 12 genes showed linear behavior within the recommended assay input range of 125 ng to 500 ng of purified RNA, with most genes showing 3% or lower quantitative bias and around 5% coefficient of variation. Total variation resulting from unique operators, reagent lots, and runs was less than 0.02 units standard deviation (SD). The performance of the analytically validated assay (AUC = 0.75) was equivalent to what we observed in the signature development dataset. The analytical performance of the assay within the specification input range demonstrated reliable quantification of the HEARTBiT score within 0.02 SD units, measured on a 0 to 1 unit scale. This assay may therefore be of high utility in clinical validation of HEARTBiT in future biomarker observational trials.

Frailty as an Immune-Mediated Condition That Leads to an Increased Risk of Acute Cellular Rejection in Liver Transplant Recipients.

Frailty as an Immune-Mediated Condition That Leads to an Increased Risk of Acute Cellular Rejection in Liver Transplant Recipients.

Post-Transplant Diabetes Mellitus and the Risk of Acute Rejection in Heart Transplant

The development of post-transplant diabetes mellitus (PTDM) is associated with an increased risk of acute rejection after kidney and liver transplantation, however, the outcomes after orthotopic heart transplant (OHT) have yet to be systematically studied. We sought to investigate whether there is any relationship between the development of PTDM and acute rejection after cardiac transplant. This was a single center retrospective review of 100 consecutive OHT patients between May 2015 and May 2018. A total of 39 patients with a documented history of diabetes mellitus were excluded from the study. Patients were divided into 2 groups: those who developed PTDM and those who did not. PTDM was defined by a hemoglobin A1C (HBA1c) ≥ 6.5 and/or a fasting blood glucose (FBG) ≥ 126 at 6 months post-transplant. Rates of rejection (ISHLT grading ≥ 1R/1B - 3R/3B) were compared between the 2 groups. Of the 61 patients (mean age 54.5 ± 11.9), 12 (19.6%) developed persistent PTDM at 6 months. Nine of the 12 patients who developed PTDM at 6 months had rejection compared to 9 of 49 patients who did not develop PTDM (75 % vs 18.37 %; p= <0.001 Figure 1). There was a positive correlation between the development of PTDM and the risk of rejection (r=0.632; p= <0.0001). Cumulative daily dose of prednisone pre-rejection as well as 6 months post-transplant was 21.4 mg ± 9.46 and 17 mg ± 10.73 respectively. Average time from OHT to rejection (N=18) was 2.3 months ± 2.47. Using adjusted regression to control for cumulative prednisone dose, age and weight, PTDM was associated with an increased risk of rejection (p= 0.002; CI 1.03-4.54). PTDM is associated with an increased risk of acute cellular rejection within 6 months post-OHT. Larger studies are warranted to examine whether any causal relationship exists between the development of PTDM and acute rejection in heart transplant recipients.

Acute Cellular Rejection after Heart Transplantation Dramatically Subsequent Risk of Mortality, Particularly among African Americans

African Americans (AA) have worse survival compared to Caucasians after heart transplantation (HTx). We assessed whether AA are at higher risk of acute cellular rejection (ACR), graft failure (GF) and cancer when compared to Caucasians and Other races in the modern era. Retrospective study in HTx recipients between 01/2008 and 05/2019 at a single institution. Outcomes included post-transplant mortality, GF, cancer and ACR. Independent estimating equations were used to analyze longitudinal biopsy differences among races. Kaplan-Meier method was used for survival and competing risk model for GF and cancer. Hazard regression was applied to quantify the association of ACR (a time dependent variable) with mortality adjusted for recipients' demographic characteristics. Among 612 recipients, 323 (56.7%) were Caucasian, 63 (11.1%) AA, and 184 (32.3%) Other. The cohort was predominantly male (71.7%), with a median (IQR) age of 55.9 (44.7 - 62.6) years. AA had a trend towards lower 5-year survival (95% CI) (AA vs. Caucasian vs. other: 77.7% [62.7%, 87.3%] vs. 80.9% [75.0%, 85.5%] vs 79.6% [71.2%, 85.7%], p= 0.49) and higher 5-year incidence of GF (AA vs. Caucasian vs. other: 13.3% [2.4%, 23.0%] vs. 8.5% [4.6%, 12.2%] vs. 6.8% [2.2%, 11.3%], p= 0.44). AA had a significantly increased risk of ACR within the first 2 years of HTx (AA vs. Caucasian vs. other (65.4% [36%, 86.4%] vs. 33.3% [25.3%, 42.3%] vs. 29.2% [18.9%, 42.2%], p< 0.001) Figure 1. Multivariable hazard regression showed that moderate and severe ACR was associated with a significant mortality risk by 14.6 [4.66-43.987] and 55.8 [5.23-590.18] fold when controlled for recipient demographics. Compared to Caucasian patients, AA were significantly more likely to have moderate-to-severe acute cellular rejection. In turn, rejection was significantly associated with post-transplant death. AA may benefit from tailored immunosuppression to reduce the risk of rejection and death.

The association between human leukocyte antigen eplet mismatches, de novo donor-specific antibodies, and the risk of acute rejection in pediatric kidney transplant recipients.

The longitudinal relationship between HLA class I and II eplet mismatches, de novo donor-specific antibodies (dnDSA) development, and acute rejection after transplantation in childhood is unknown. Eplet mismatches at HLA class I and II loci were calculated retrospectively for each donor/recipient pair transplanted between 2005 and 2015 at a single Australian center. Logistic regression analyses were conducted to determine the association between the number of eplet mismatches, dnDSA, and acute rejection. The cohort comprised 59 children (aged 0-18years) who received their first kidney allograft and were followed for median (interquartile range) 4.5 (± 2.6) years. Overall, 32% (19/59) developed dnDSA (class I 3% (2/59), class II 14% (8/59), 15% class I and II (9/59)), and 24% (14/59) developed biopsy-proven acute rejection. Every unit increase in class I and II eplet mismatches corresponded to an increase in risk of class I (odds ratio (OR) 1.22, 95% CI 1.07-1.39, p < 0.01) and class II (OR 1.06, 95% CI 1.01-1.11, p = 0.02) dnDSA development. Compared with recipients without dnDSA, class I and II dnDSA were associated with direction of effect towards increased risk of acute cellular rejection (class I: OR 5.87, 95% CI 0.99-34.94, p = 0.05; class II: OR 12.00, 95% CI 1.25-115.36, p = 0.03) and acute antibody-mediated rejection (class I: OR 25.67, 95% CI 3.54-186.10, p < 0.01; class II: OR 9.71, 95% CI 1.64-57.72, p = 0.01). Increasing numbers of HLA class I or II eplet mismatches were associated with the development of dnDSA. Children who developed dnDSA were also more likely to develop acute rejection compared with children without dnDSA.

Vitamin D supplementation could reduce the risk of acute cellular rejection and infection in vitamin D deficient liver allograft recipients

BackgroundVitamin D regulates the immune system and affects the outcome of allografts. We investigated the mechanisms underlying the preventative potential of vitamin D in acute cellular rejection (ACR) and infection, and determined its effects on the induction of both T cells and complement. MethodsA total of 141 patients who received a liver allograft at our center between 2012 and 2016 were enrolled in the study and divided into a vitamin D supplementation group (case group, n = 71) and a non-vitamin D supplementation group (control group, n = 70). Serum was collected in the hours prior to transplantation and within the first month of transplantation. We evaluated the relationship between the serum levels of 25-hydroxyvitamin D ACR, infection, T cells, complement, and graft function. Follow-up was conducted until patient death or June 30, 2018. ResultsVitamin D deficiency was an important independent risk factor for ACR. The incidence of ACR, and bacterial and fungal infection was reduced in patients with vitamin D supplementation. The frequency of Treg, Tmemory, T naïve cells and CD8 + CD28+ T cells (CTL) and the level of complement component 3 were related to ACR in the first month after transplantation. This study showed increased numbers of Treg cells and Tmemory cells and decreased numbers of Naïve cells and CTL in the case group. Vitamin D status was significantly associated with mortality. ConclusionsVitamin D supplementation is associated with a lower risk of ACR and infection, suggesting that it may promote immune tolerance towards the liver allografts.

High Body Mass Index is a Risk Factor for Acute Cellular Rejection in Lung Transplant Recipients

High body mass index (BMI) is associated with increased risk of acute cellular rejection (ACR) in renal and cardiac transplant recipients. Despite advances in immunosuppressive therapies, ACR continues to occur in more than a third of recipients in the first year post lung transplant (LTx). Although there is data on the association between primary graft dysfunction and obesity in LTx, the effect of BMI on the incidence of ACR has not been examined.

(900) - Variability in Gene Expression Profiling (GEP) Identifies Heart Transplant Recipients at Risk for Acute Cellular Rejection but Not Cardiac Allograft Vasculopathy

(900) - Variability in Gene Expression Profiling (GEP) Identifies Heart Transplant Recipients at Risk for Acute Cellular Rejection but Not Cardiac Allograft Vasculopathy

Donor Liver Small Droplet Macrovesicular Steatosis Is Associated With Increased Risk for Recipient Allograft Rejection.

Although donor livers with <30% large droplet macrovesicular steatosis (MaS) and/or small droplet MaS (irrespective of percentage) are considered safe to use, this consensus is based on variable definitions of MaS subtypes and/or without a reproducible scoring system. We analyzed 134 donor liver biopsies from allografts transplanted at University of California at San Francisco between 2000 and 2015 to determine whether large and/or small droplet MaS is a risk factor for poor outcomes. Large droplet MaS was defined as a fat droplet occupying greater than one half of an individual hepatocyte, with nuclear displacement, and scored as the percentage of total parenchymal area replaced by large fat droplets on ×40 magnification. Small droplet MaS was defined as 1 to several discrete fat droplets, each occupying less than one half of an individual hepatocyte, and scored as the percentage of remaining hepatocytes (ie, hepatocytes not occupied by large fat droplets) containing small fat droplets on ×200 magnification (ie, small droplet MaS is the percentage of "remaining hepatocytes" with small fat droplets, and "remaining hepatocytes" is defined as 100% minus percent large droplet MaS). Thus, total MaS equals the sum of large and small droplet MaS, which cannot exceed 100%. Electronic medical records were reviewed to determine outcomes. There was an increased risk for acute cellular rejection (hazard ratio=2.5, P=0.0108) and bile duct loss suggestive of chronic ductopenic rejection (hazard ratio=2.4, P=0.0130) in donor livers with ≥30% small droplet MaS. Large droplet MaS (up to 60%) was not associated with adverse outcomes. Patient survival was not adversely affected by steatosis. Excellent agreement on the estimation of large (weighted κ=0.682) and small droplet MaS (weighted κ=0.780) was achieved. Our approach to donor steatosis scoring can identify liver allograft recipients at increased risk for rejection and highlights the importance of distinguishing between small and large droplet MaS in this evaluation.