Liver Allograft Research Articles

Liver allograft pathology in the late post-transplant period

Annually increasing quantity of liver transplants and the growing population of long-survived recipients determine the relevance of late allograft dysfunction study. Variety of morphological and functional disorders of the transplanted liver complicates their timely diagnostics. Moreover, in some patients, serious graft damage may proceed for a long time without clinical manifestations and laboratory abnormalities.The review summarizes the structure, prevalence, risk factors and prognostic value of different liver allograft pathology determined by histological examination in the long term after transplantation.

Early patient and liver allograft outcomes from donation after circulatory death donors using thoracoabdominal normothermic regional: a multi-center observational experience.

Donation after circulatory death (DCD) liver allografts are associated with higher rates of primary non-function (PNF) and ischemic cholangiopathy (IC). Advanced recovery techniques, including thoracoabdominal normothermic regional perfusion (TA-NRP), may improve organ utilization and patient and allograft outcomes. Given the increasing US experience with TA-NRP DCD recovery, we evaluated outcomes of DCD liver allografts transplanted after TA-NRP. Liver allografts transplanted from DCD donors after TA-NRP were identified from 5/1/2021 to 1/31/2022 across 8 centers. Donor data included demographics, functional warm ischemic time (fWIT), total warm ischemia time (tWIT) and total time on TA-NRP. Recipient data included demographics, model of end stage liver disease (MELD) score, etiology of liver disease, PNF, cold ischemic time (CIT), liver function tests, intensive care unit (ICU) and hospital length of stay (LOS), post-operative transplant related complications. The donors' median age was 32 years old and median BMI was 27.4. Median fWIT was 20.5 min; fWIT exceeded 30 min in two donors. Median time to initiation of TA-NRP was 4 min and median time on bypass was 66 min. The median recipient listed MELD and MELD at transplant were 22 and 21, respectively. Median allograft CIT was 292 min. The median length of follow up was 257 days. Median ICU and hospital LOS were 2 and 7 days, respectively. Three recipients required management of anastomotic biliary strictures. No patients demonstrated IC, PNF or required re-transplantation. Liver allografts from TA-NRP DCD donors demonstrated good early allograft and recipient outcomes.

Comparing High- and Low-Model for End-Stage Liver Disease Living-Donor Liver Transplantation to Determine Clinical Efficacy: A Systematic Review and Meta-Analysis (CHALICE Study).

Various studies have demonstrated that low-Model for End-Stage Liver Disease (MELD) living-donor liver transplant (LDLT) recipients have better outcomes with improved patient survival than deceased-donor liver transplantation (DDLT) recipients. LDLT recipients gain the most from being transplanted at MELD <25-30; however, some existing data have outlined that LDLT may provide equivalent outcomes in high-MELD and low-MELD patients, although the term "high" MELD is arbitrarily defined in the literature and various cut-off scores are outlined between 20 and 30, although most commonly, the dividing threshold is 25. The aim of this meta-analysis was to compare LDLT in high-MELD with that in low-MELD recipients to determine patient survival and graft survival, as well as perioperative and postoperative complications. Following PROSPERO registration CRD-42021261501, a systematic database search was conducted for the published literature between 1990 and 2021 and yielded a total of 10 studies with 2183 LT recipients; 490 were HM-LDLT recipients and 1693 were LM-LDLT recipients. Both groups had comparable mortality at 1, 3 and 5 years post-transplant (5-year HR 1.19; 95% CI 0.79-1.79; p-value 0.40) and graft survival (HR 1.08; 95% CI 0.72, 1.63; p-value 0.71). No differences were observed in the rates of major morbidity, hepatic artery thrombosis, biliary complications, intra-abdominal bleeding, wound infection and rejection; however, the HM-LDLT group had higher risk for pulmonary infection, abdominal fluid collection and prolonged ICU stay. The high-MELD LDLT group had similar patient and graft survival and morbidities to the low-MELD LDLT group, despite being at higher risk for pulmonary infection, abdominal fluid collection and prolonged ICU stay. The data, primarily sourced from high-volume Asian centers, underscore the feasibility of living donations for liver allografts in high-MELD patients. Given the rising demand for liver allografts, it is sensible to incorporate these insights into U.S. transplant practices.

Dysfunctional Cori and Krebs cycle and inhibition of lactate transporters constitute a mechanism of primary nonfunction of fatty liver allografts

Orthotopic liver transplantation (OLT) is a lifesaving procedure. However, grafts may fail due to primary nonfunction (PNF). In the past, we demonstrated PNFs to be mainly associated with fatty allografts, and given its unpredictable nature, the development of a disease model is urgently needed. In an effort to investigate mechanism of fatty allograft-associated PNFs, we induced fatty liver disease in donor animals by feeding rats a diet deficient in methionine and choline (MCD). We performed OLT with allografts of different grades of hepatic steatosis and compared the results to healthy ones. We assessed liver function by considering serum biochemistries, and investigated genome wide responses following OLT of healthy and fatty allograft-associated PNFs. Furthermore, we performed immunohistochemistry to evaluate markers of oxidative stress and reperfusion injury, inflammation, glycolysis and gluconeogenesis, lactate transport, and its utilization as part of the Cori cycle. Strikingly, PNFs are strictly lipid content dependent. Nonetheless, a fat content of ≤17% and an increase in the size of hepatocytes of ≤11% (ballooning) greatly improved outcome of OLTs and the hepatic microcirculation. Mechanistically, PNFs arise from a dysfunctional Cori cycle with complete ablation of the lactate transporter SLC16A1. Thus, lipid-laden hepatocytes fail to perform gluconeogenesis via lactate reutilization, and the resultant hyperlactatemia and lactic acidosis causes cardiac arrhythmogenicity and death. Furthermore, the genomic and immunohistochemistry investigations underscore a dysfunctional Krebs cycle with impaired energy metabolism in lipid-burdened mitochondria. Together, we show fatty allografts to be highly vulnerable towards ischemia/reperfusion-injury, and stabilizing the Cori cycle is of critical importance to avert PNFs.

Temporal and spatial dynamics of immune cells in spontaneous liver transplant tolerance

The liver has long been deemed a tolerogenic organ. We employed high-dimensional mass cytometry and immunohistochemistry to depict the temporal and spatial dynamics of immune cells in the spleen and liver in a murine model of spontaneous liver allograft acceptance. We depicted the immune landscape of spontaneous liver tolerance throughout the rejection and acceptance stages after liver transplantation and highlighted several points of importance. Of note, the CD4+/CD8+ Tcell ratio remained low, even in the tolerance phase. Furthermore, a PhenoGraph clustering analysis revealed that exhausted CD8+ Tcells were the most dominant metacluster in graft-infiltrating lymphocytes (GILs), which highly expressed the costimulatory molecule CD86. The temporal and spatial dynamics of immune cells revealed by high-dimensional analyses enable a fine-grained analysis of GIL subsets, contribute to new insights for the discovery of immunological mechanisms of liver tolerance, and provide potential ways to achieve clinical operational tolerance after liver transplantation.

24-hour normothermic machine perfusion of discarded human liver grafts: Case series single-center study

BackgroundThe persistent shortage of liver allografts contributes to significant waitlist mortality. Normothermic machine perfusion (NMP) has the potential to extend viability and allow liver function evaluation in discarded organs. The main aim of the study was to evaluate the possibility for extended preservation and the potential recovery of non-usable human livers utilizing NMP. Methods6 high-risk human liver grafts that were discarded after national allocation underwent normothermic liver preservation for an extended period of 24 h. Transmedics Organ Care System™ liver perfusion device was used to preserve a donor liver in a functioning, near physiologic state. Parameters of biochemical and synthetic liver function were collected periodically and subsequently analyzed. Liver parenchyma and bile duct biopsies were obtained pre- and 24 h post-NMP. Results4/6 (67%) grafts were DCDs with a median age of 54 (IQR: 42–61) years and median CIT of 262 (IQR: 209–1024) minutes. 5/6 (83%) livers produced a median of 75 ml of bile (Range 55–100) after 24 h of NMP. Lactate dropped to normal levels (<2 mmol/L) for all livers after around 4 h on NMP. The overall cellular architecture, lobular steatosis and necrosis grades were preserved after extended NMP. Biopsies showed improvement of liver parenchyma architecture with reduced inflammation for 2/6 (33%) at the end of the perfusion. ConclusionProlonged NMP for discarded liver grafts can be safely maintained on NMP and may identify certain grafts that are suitable for transplantation. Further studies utilizing NMP with subsequent transplantation would validate this strategy, as well as existing viability markers.

Impact of Portable Normothermic Machine Perfusion for Liver Transplantation From Adult Deceased Donors.

To assess how liver allografts preserved using portable normothermic machine perfusion (NMP) compare against those that underwent ischemic cold storage (ICS) in the setting of donation after brain death (DBD) and donation after circulatory death (DCD) liver transplantation (LT). Compared with conventional ICS, NMP may offer more homeostatic preservation, permit physiological assessment of organ function, and provide opportunities for graft improvement/modification. We report a single-center US experience of liver NMP. A single-center, retrospective analysis of collected data on 541 adult whole LTs from 469 DBD donors [NMP (n = 58) vs ICS (n = 411)] and 72 DCD donors [NMP (n = 52) vs ICS (n = 20)] between January 2016 and December 2022. In DBD LT, male sex [odds ratio (95% CI): 1.83 (1.08-3.09)] and >10% macrosteatosis of the donor liver [1.85 (1.10-3.10)] were statistically significant independent risk factors of early allograft dysfunction (EAD). Donor age >40 years and cold ischemia time >7 hours were independent risk factors of reperfusion syndrome (RPS). One-year, 3-year, and 5-year incidences of ischemic cholangiopathy (IC) did not differ significantly in DBD cases between the NMP and ICS cohorts. In DCD LT, NMP was an independent protective factor against EAD [0.11 (0.03-0.46)] and RPS [0.04 (0.01-0.25)]. The incidence of IC in the DCD cases at 1-year and 3-year time points was significantly lower in the NMP cohort (1.9% compared with 20% in the ICS group). Compared with conventional ICS, NMP can significantly reduce the incidence of EAD, RPS, and IC after DCD LT.

Impact of immunosuppression level on liver allograft fibrosis after pediatric liver transplantation: a retrospective cohort study.

Liver allograft fibrosis (LAF) is prevalent among children with long-term survival after liver transplantation (LT). The authors aimed to identify clinical risk factors, with a focus on the impact of immunosuppression (IS) level in the early post-transplant period on LAF. A retrospective study was conducted on pediatric LT recipients with at least 1-year of follow-up. Cox regression models were used to analyze risk factors associated with LAF, and landmark analysis was used to evaluate the impact of IS level on LAF. Longitudinal analysis was also conducted in patients with paired biopsies. A total of 139 patients involving 174 liver biopsies were included. With 2.3 to 5.9 years of follow-up, LAF was detected in 91.4% of patients (7.9% were significant), up to 88.2% of whom showed normal liver function. Episodes of acute rejection, biliary complications, cytomegalovirus infection, and prolonged cold ischemia time were independent risk factors. Besides, the risk of LAF in patients with relatively low IS levels at postoperative 1-3, 3-6, 6-12, and 12-36 months was higher than the counterparts. Especially, in patients with relatively high IS levels (mean tacrolimus trough concentration ≥5.1ng/ml) during postoperative 12-36 months, the risk of LAF was 67% lower in the short future ( P =0.006). In paired analysis, patients with increased IS levels were more likely to achieve fibrosis-reduction (HR=7.53, P =0.025). Mild to moderate LAF is common among pediatric LT recipients and can appear early and silently. Maintaining adequate levels of IS during 1-3 years after LT seems crucial to ensure protection against LAF.

Postinfantile Giant Cell Hepatitis in Native and Allograft Livers: A Multi-Institutional Clinicopathologic Study of 70 Cases

Postinfantile giant cell hepatitis (PIGCH) is a rare hepatitis pattern in adults with variable etiologies and clinical outcomes. We conducted a multi-institutional retrospective study to define the clinicopathologic characteristics of patients with PIGCH. A total of 70 PIGCH cases were identified and reviewed for pathological features, including fibrosis, cholestasis, inflammation, steatosis, necrosis, and apoptosis, as well as the distribution of giant cells and the maximum number of giant cells per high-power field. Demographic and clinical data, including age, sex, laboratory results, etiologies, and follow-up results, were recorded. Among the 70 cases, 40% (28/70) were associated with autoimmune liver diseases, followed by 9 (13%) with unknown etiology, 8 (11%) with viral infection, 5 (7%) with medications, 5 with combined etiologies, and 4 (6%) with malignancies (mostly chronic lymphocytic leukemia). Notably, another 16% were de novo PIGCH in liver allografts, most of which occurred after a rejection event. During follow-up, 26 (37%) patients died of the disease and 44 (63%) were alive. Deceased patients were characterized by older age (mean age, 54.9 vs 45.5 years; P = .02), higher alkaline phosphatase level (mean value, 253.3U/L vs 166.3 U/L; P = .03), higher fibrosis stage (stage 3-4 vs stage 0-2, 57.7% vs 29.6%; P = .03), being more likely to have de novo PIGCH after transplantation (23.1% vs 11.4%; P = .04), and being less likely to have primary autoimmune liver disease etiology (26.9% vs 47.7%; P = .04). These results indicate that PIGCH is a rare pattern of liver injury associated with different etiologies and variable clinical outcomes. Autoimmune liver disease with PIGCH is associated with better survival, whereas de novo PIGCH in allografts is associated with poorer survival. Older age, higher alkaline phosphatase level, and advanced fibrosis are adverse prognostic factors.

A Rare Case of Donor-Origin Intrahepatic Cholangiocarcinoma After Liver Transplantation for Hepatocellular Carcinoma: A Case Report

Tumors may develop in the grafted liver after liver transplantation for hepatocellular carcinoma, most of which are hepatocellular carcinoma recurrences and are rarely of donor origin. We report a rare case of donor-origin intrahepatic cholangiocarcinoma in a liver allograft after liver transplantation for hepatocellular carcinoma. A man in his 60s underwent liver transplantation for hepatocellular carcinoma with hepatitis C virus cirrhosis. The donor was a braindead woman in her 60s who had no history of malignancy. Three years and 5 months after liver transplantation, a tumor developed in the allograft. Computed tomography scans showed a 40-mm tumor that was atypical for hepatocellular carcinoma. Tumor biopsy was most suggestive of intrahepatic cholangiocarcinoma. Fluorescence in situ hybridization of the tumor showed an XX signal pattern, suggesting that it originated from the donor liver. Whole exome sequencing analysis strongly suggested that the tumor was an intrahepatic cholangiocarcinoma derived from the donor. Although donor-origin cancer after liver transplantation is extremely rare, it should be considered for adequate treatment.

Luteolin attenuates acute liver allograft rejection in rats by inhibiting T cell proliferation and regulating T cell subsets.

Allograft rejection continues to be a significant cause of morbidity and graft failure for liver transplant recipients. Existing immunosuppressive regimens have many drawbacks, thus safe and effective long-term immunosuppressive regimens are still required. Luteolin (LUT), a natural component found in many plants, has a variety of biological and pharmacological effects and shows good anti-inflammatory activity in inflammatory and autoimmune diseases. Nevertheless, it remains unclear how it affects acute organ rejection after allogeneic transplantation. In this study, a rat liver transplantation model was constructed to investigate the effect of LUT on acute rejection of organ allografts. We found that LUT significantly protected the structure and function of liver grafts, prolonged recipient rat survival, ameliorated T cell infiltration, and downregulated proinflammatory cytokines. Moreover, LUT inhibited the proliferation of CD4+ T cells and Th cell differentiation but increased the proportion of Tregs, which is the key to its immunosuppressive effect. In vitro, LUT also significantly inhibited CD4+ T cell proliferation and Th1 differentiation. There may be important implications for improving immunosuppressive regimens for organ transplantation as a result of this discovery.

Paired Exchange Liver Transplantation Using an Altruistic Living Donor: First Case in Saudi Arabia—A Case Report

Paired exchange (PE) living donor organ transplantation is an innovation designed to expand the pool of organs available for transplantation. In PE liver transplantation, the donor organs are exchanged between the 2 pairs to overcome blood group incompatibility or volume mismatch. There are ethical and logistic issues surrounding PE. This is the first report of PE liver transplantation in Saudi Arabia using an altruistic donor (AD). The AD may facilitate the exchange because there is no reciprocal expectation of transplantation from the AD. Paired exchange may increase only a small number of donated liver allografts. This may be the only solution for some families and in some countries.

Histopathology of Budd-Chiari Syndrome.

The histopathological changes in Budd-Chiari syndrome (BCS) overlap with those of sinusoidal obstruction syndrome (SOS) and of cardiac or pericardiac disorders resulting in right cardiac failure. These conditions, however, are different on both clinical and pathological grounds and need to be differentiated from BCS. This review is centred on the three main aspects of BCS in diagnostic liver histopathology: (1) general histopathology of BCS; (2) implications for liver biopsy interpretation; and (3) BCS in the liver allograft. The histological features of BCS form a complex spectrum which is shaped differently in each individual case according to the topographical distribution and chronological evolution of the obliterative insult, its upstream effect of the hepatic vascularisation and the consequent parenchymal injury, scarring and remodelling. Sampling variation limits the use of liver biopsy for prognostication in patients with BCS.

Biomarkers of the Complement System Activation (C3a, C5a, sC5b-9) in Serum of Patients before and after Liver Transplantation.

The liver has a huge impact on the functioning of our body and the preservation of homeostasis. It is exposed to many serious diseases, which may lead to the chronic failure of this organ, which is becoming a global health problem today. Currently, the final form of treatment in patients with end-stage (acute and chronic) organ failure is transplantation. The proper function of transplanted organs depends on many cellular processes and immune and individual factors. An enormous role in the process of acceptance or rejection of a transplanted organ is attributed to, among others, the activation of the complement system. The aim of this study was the evaluation of the concentration of selected biomarkers' complement system activation (C3a, C5a, and sC5b-9 (terminal complement complex)) in the serum of patients before and after liver transplantation (24 h, two weeks). The study was conducted on a group of 100 patients undergoing liver transplantation. There were no complications during surgery and no transplant rejection in any of the patients. All patients were discharged home 2-3 weeks after the surgery. The levels of all analyzed components of the complement system were measured using the ELISA method. Additionally, the correlations of the basic laboratory parameters-C-reactive protein (CRP), hemoglobin (Hb), total bilirubin, alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGTP), and albumin-with the parameters of the complement system (C3a, C5a, and sC5b-9) were determined. In our study, changes in the concentrations of all examined complement system components before and after liver transplantation were observed, with the lowest values before liver transplantation and the highest concentration two weeks after. The direct increase in components of the complement system (C3a, C5a, and sC5b-9) 24 h after transplantation likely affects liver damage after ischemia-reperfusion injury (IRI), while their increase two weeks after transplantation may contribute to transplant tolerance. Increasingly, attention is being paid to the role of C3a and CRP as biomarkers of damage and failure of various organs. From the point of view of liver transplantation, the most interesting correlation in our own research was found exactly between CRP and C3a, 24 h after the transplantation. This study shows that changes in complement activation biomarkers and the correlation with CRP in blood could be a prognostic signature of liver allograft survival or rejection.

Association of torque teno virus viremia with liver fibrosis in the first year after liver transplantation.

Torque teno virus (TTV) replication is controlled by immune status, mirroring a degree of immunosuppression after solid organ transplantation. TTV viraemia (TTVv) was associated with acute cellular rejection and infection within the first year after liver transplantation (LT). Long-term data on TTV after LT and correlation with graft injury from protocol biopsies are limited. One hundred plasma samples paired with graft biopsies from a prospective single-center biorepository were analyzed. The median time post-LT was 23 months (range, 2-298). TTVv was detectable in 97%. TTVv decreased over time after LT and showed a significant decline from year 1 to later time points. Hence, TTVv correlated negatively with histologic liver fibrosis (liver allograft fibrosis and Ishak scores) and positively with the overall immunosuppression degree quantified by an immunosuppression score in the first year after LT. There was no association with dosages or trough levels of single immunosuppressants. The pharmacodynamic marker TTVv did not correlate with pharmacokinetic assessments of immunosuppression degree [calcineurin inhibitor (CNI) trough levels or immunosuppressant dosages]-our clinical gold standards to guide immunosuppressive therapy. TTVv was independently associated with histologically proven liver fibrosis after LT in the first year after LT in multivariate analysis. The independent association of histological graft fibrosis with lower TTVv in year 1 underscores that a pharmacodynamic marker would be preferable to individualize immunosuppression after LT. However, a high variability of TTVv at the low immunosuppression doses given after the first year precludes TTV as a clinically useful marker after LT in the long-term liver transplant recipients.

Detailed Analysis of Simultaneous Renal and Liver Allografts in the Presence of DSA.

We reevaluated allograft biopsies from simultaneous liver-kidney transplant recipients who had both allografts biopsied within 60 d of one another and within 30 d of DSA being positive in serum (positive: mean florescence intensity ≥5000). Routine histology, C4d staining, and specialized immunohistochemistry for Kupffer cells (KCs; CD163) and a C4d receptor immunoglobulin-like transcript-4 were carried out in 4 patients with 6 paired biopsies. Overt antibody-mediated rejection was found in 3 of 4 renal and liver allografts. One patient had biopsy-confirmed renal and liver allograft antibody-mediated rejection despite serum clearance of DSA. All biopsies showed KC hypertrophy (minimal: 1; mild: 2; moderate: 1; severe: 2) and cytoplasmic C4d KC staining was easily detected in 2 biopsies from 2 patients; minimal and negative in 2 biopsies each. Implications of which are discussed. Control 1-y protocol liver allograft biopsies from DSA- recipients showed neither KC hypertrophy nor KC C4d staining (n = 6). Partial renal allograft protection by a liver allograft from the same donor may be partially mediated by phagocytosis/elimination of antibody and complement split products by KCs, as shown decades ago in controlled sensitized experimental animal experiments.

Balancing immunosuppression in pediatric liver transplantation: Playing the long game.

The overarching goal in the care of pediatric liver transplant recipients is to optimize allograft and patient health. Balancing immunosuppression to maintain allograft health while avoiding medication side effects is essential for long-term survival and optimal quality of life in pediatric liver transplant recipients. Utilizing precision medicine to personalize immunosuppression, which includes minimization and withdrawal, is core to this effort. The unique anatomy and physiology of the liver make it more tolerant to immune-mediated injury and a more favorable organ for immunosuppression minimization and withdrawal. However, several challenges exist. Standard biochemical values and histologic features may not reliably predict allograft health after a reduction in immunosuppression. Additionally, biochemical values alone do not reliably identify which patients can successfully develop operational tolerance, as there may be occult allograft injury despite normal liver enzymes. Finally, the durability of tolerance after successful reduction in immunosuppression remains uncertain over time. Innovative tools show promise in circumventing these challenges, but more research is needed to determine actual clinical utility. While immunosuppression-free transplant may not be a current reality for most pediatric liver transplant recipients, strategies to safely minimize immunosuppression without compromising allograft health are within reach. Each liver allograft and recipient pair requires a different degree of immune modulation, and through a structured process of minimization and withdrawal, immunosuppression can indeed be tailored in a precise, personalized way to optimize outcomes. This review focuses on the progress that has been made to individualize immunosuppression in pediatric liver transplantation to ensure optimal allograft and recipient health.

Donor Diabetes and Steatosis Affects Recipient Survival Following Liver Transplantation Based on Etiology of Liver Cirrhosis.

Liver transplantation (LT) offers patients with decompensated cirrhosis the best chance at long-term survival. With the rising prevalence of diabetes, further clarity is needed on the impact of receiving a liver allograft from a donor with diabetes on post-LT outcomes. This study aims to evaluate the impact of donor diabetes on clinical outcomes after LT. This is a retrospective analysis of the United Network for Organ Sharing registry data of LT recipients from January 1, 2000, to December 31, 2021. Outcomes analysis was performed using Cox proportional model for all-cause mortality and graft failure. Confounding was reduced by coarsened exact matching causal inference analysis. Of 66 960 donors identified, 7178 (10.7%) had diabetes. Trend analysis revealed a longitudinal increase in the prevalence of donor diabetes ( P < 0.001). Importantly, donor diabetes was associated with increased all-cause mortality (hazard ratio [HR]: 1.13; 95% confidence interval [CI], 1.07-1.19; P < 0.001) and graft failure (HR: 1.16; 95% CI, 1.11-1.22; P < 0.001). Receiving donor organ with diabetes reduced graft survival in patients who received LT for nonalcoholic steatohepatitis cirrhosis (HR: 1.26; 95% CI, 1.13-1.41; P < 0.001) but not other etiologies of cirrhosis. Donor diabetes was associated with worse outcomes post-LT, particularly in patients receiving LT for nonalcoholic steatohepatitis cirrhosis. Future studies are needed to better understand the mechanism underlying this association to develop better risk stratification and clinical practice to improve the outcomes of the transplanted patients.

Extracorporeal membrane oxygenation for cardiopulmonary failure in organ donation: Assessing liver transplant outcomes.

Liver transplantation continues to face significant organ shortages and efficient utilization of marginal donors is paramount. This study evaluates the practice patterns and outcomes in liver transplantation when utilizing allografts from marginal donors who required extracorporeal membrane oxygenation (ECMO) support. We performed a retrospective review of the Gift of Life (PA, NJ, DE) organ-procuring organization database for transplants performed using donors supported on ECMO for nondonation purposes. These were cross-referenced to the transplant recipients within the Organ Procurement and Transplantation Network database, and the outcomes of liver transplants using donors on ECMO support were compared with those not requiring ECMO. Organ use and nonuse patterns were then evaluated in ECMO-supported donors, identifying the factors associated with nonuse compared with the factors associated with graft failure. Thirty-nine of the 84 ECMO-supported donors contributing at least one intra-abdominal organ for transplant donated a liver. Graft survival and patient survival up to 5 years were comparable between transplants from ECMO and non-ECMO-supported donors, and no cases of primary nonfunction were seen in the ECMO group. ECMO support was not associated with 1-year graft failure on regression modeling. Additional regression analyses within the ECMO donor population identified bacteremia (HR: 19.81) and elevated total bilirubin at donation (HR: 2.44) as predictive of post-transplant graft failure. Livers from donors supported on ECMO before donation appear safe to use in select transplant settings. Better understanding of the impact of predonation ECMO on liver allograft function will help guide the optimal use of these scarcely used donors.

Successful treatment of acute antibody-mediated rejection of liver allograft with imlifidase: A case report

Although the incidence of acute antibody mediated rejection in liver transplantation is low, the consequences of acute antibody mediated rejection can be devastating, often leading to severe fibrotic changes and early graft loss. Conventional treatment modalities for management of moderate-to-severe acute antibody mediated rejection in liver transplant continue to rely on of corticosteroids, plasmapheresis, and intravenous immunoglobulin. However, management of refractory, severe antibody mediated rejection remains without a clear gold-standard approach. This case report describes successful first use of Imlifidase, an Ig-G degrading enzyme, for management of acute refractory antibody mediated rejection following orthotopic liver transplant. This 41-year-old woman developed acute antibody meditated rejection and donor specific antibodies within two weeks of undergoing an A2 to O liver transplant. Following unsuccessful treatment with conventional modalities, treatment with Imlifidase resulted in normalization of liver function, resolution of antibody mediated rejection on surveillance biopsy, and disappearance of donor specific antibodies. Imlifidase could represent a promising treatment for refractory antibody mediated rejection in liver transplantation and warrants further study.