Treatment For End-stage Liver Disease Research Articles

Expert Consensus on Diagnosis and Treatment of End-Stage Liver Disease Complicated with Infections

Abstract End-stage liver disease (ESLD) is a life-threatening clinical syndrome that markedly increases mortality in patients with infections. In patients with ESLD, infections can induce or aggravate the occurrence of liver decompensation. Consequently, infections are among the most common complications of disease progression. There is a lack of working procedure for early diagnosis and appropriate management for patients with ESLD complicated by infections as well as local and international guidelines or consensus. This consensus assembled up-to-date knowledge and experience across Chinese colleagues, providing data on principles as well as working procedures for the diagnosis and treatment of patients with ESLD complicated by infections.

Diagnostic Value and Clinical Application of mNGS for Post-Liver Transplantation Infection: A Cross-Sectional Study With Case Reports.

Liver transplantation is widely acknowledged as the only effective treatment for end-stage liver disease, and infection is reportedly an important cause of postoperative death. Clinical use of metagenomic next-generation sequencing (mNGS) to diagnose postoperative infection and successfully guide drug therapy remains rare. This study included patients with infectious complications after liver transplantation from July 2019 to December 2020 and was divided into three groups: pneumonia, unknown fever, and others (including hepatic failure, kidney failure, cirrhosis after LT, and other postoperative complications that predispose to infection). The mNGS sequencing was used to detect microorganisms, and the results were compared with traditional culture. We found that mNGS yielded improved sensitivity over culture (85.19 vs. 22.22%; p<0.0001) but lower specificity (35.71 vs. 89.28%; p<0.0001). Among the 48 kinds of pathogens detected, the Torque teno virus 22 (15/122) was the most common, followed by Primate erythroparvovirus 1 (13/122). The top four bacteria included Klebsiella pneumoniae (n = 8), Enterococcus faecium (n = 5), Stenotrophomonas maltophilia (n = 4), and Escherichia coli (n = 4). Aspergillus fumigatus was the most common fungus. The bronchoalveolar lavage fluid (BALF) exhibited the highest proportion of positive findings among sample types, with viral, fungal, and bacterial mixed infection being the most common (n = 6, 19.35%). Besides, using mNGS for early diagnosis of infection after liver transplantation may effectively prolong patient survival. This is the first study to explore the application value of mNGS and its comparison with traditional culture in pneumonia and other infections in post-liver transplantation patients. The simultaneous application of these two methods suggested that the Torque teno virus 22, Klebsiella pneumoniae, and the Aspergillus fumigatus are the most common pathogens of viruses, bacteria, and fungi after LT, suggesting that these pathogens may be associated with postoperative pathogen infection and patient prognosis. The mNGS technique showed distinct advantages in detecting mixed, viral, and parasitic infections in this patient population. Further studies are warranted to systematically elucidate the dynamic evolution and molecular characteristics of infection after liver transplantation.

Clinicopathological analysis of ischemia/reperfusion time-zero injury biopsies and its role in early allograft dysfunction in hepatic transplantation (retrospective cross-sectional study)

Background and objectives Orthotropic liver transplantation is the only choice for treatment of end-stage liver diseases. B cell lymphoma 2 (BCL2) is a protein that regulates apoptosis. We aim to pinpoint the role of time-zero biopsies in predicting early graft dysfunction following liver transplantation by evaluation of BCL2 expression in hepatocyte. Patients and methods Thirty seven liver biopsies were evaluated histopathologically for ischemia–reperfusion injury and immunohistochemically by expression of BCL2. Results Out of 37 cases studied, 33 (89.2%) males and four (10.8%) females with a mean±SD age of 46.48 ± 12.05 years old. Their alanine aminotransferase average was 137.56 ± 76.46 U/l, the aspartate aminotransferase average was 62.84 ± 58.26 U/l, while international normalized ratio average was 1.79 ± 0.59. Histopathology shown, ballooning degeneration in 28 (75.7%), apoptosis was negative in 12 (32.4%), few in 13 (35.1%), and many in 12 (32.4%). Immunostaining with anti-BCL2 antibodies for apoptotic hepatocytes was negative in 12 (32.4%) and positive in 25 (67.6%). BCL2 expression was significantly higher with ballooning degeneration (P=0.019). BCL2 expression was significantly higher with apoptosis (P&lt;0.001). Alanine aminotransferase, aspartate aminotransferase, and bilirubin levels were significantly higher with positive BCL2 expression (P=0.002, 0.025, and 0.002, respectively) and with positive ischemia/reperfusion injury (moderate or severe changes) (P=0.005, 0.032, and 0.008, respectively). Conclusion Liver pathology biopsy remains the ‘gold standard’ for the diagnosis of allograft dysfunction as when the clinical picture, liver enzymes, and imaging parameters are unclear.

Comparison of liver regeneration between donors and recipients after adult right lobe living-donor liver transplantation.

Living-donor liver transplantation (LDLT) is recognized as the standard treatment for end-stage liver diseases. The regeneration of the residual liver and graft after LDLT is important in evaluating surgical success. Previous studies have attempted to elucidate mechanisms, principles of liver regeneration after LDLT, or influencing factors. However, they have not ruled out patients with complications and reached a uniform conclusion. In this study, for the first time, we unified measurement methods of liver volumes and eliminated patients with complications to compare liver regeneration trends between donors and recipients after LDLT and search for potential influencing factors. A total of 61 donors and 62 recipients without complications after adult right lobe LDLT were included in this retrospective observational cohort study. The liver regeneration ratios (LRRs) at different time points in donors and recipients after LDLT were calculated and compared. Factors that affect LRRs include gender, age, graft with or without the middle hepatic vein (MHV), initial remnant liver (IRLV)/estimated standard liver volume (ESLV), initial graft volume (IGV)/ESLV, Child-Pugh grade, and model for end-stage liver disease (MELD) score of the recipients. Analysis of variance, independent-sample t-test, and correlation analysis were performed for statistical analyses. Significant differences were found in LRRs between the donors and recipients after LDLT (all P<0.05). The LRRs of donors at 0.5, 1, 3, and 6 months were 80.80%±24.12% (72.87%, 88.73%), 98.62%±37.47% (75.97%, 121.26%), 103.34%±23.47% (83.73%, 122.96%), and 130.18%±17.68% (102.04%, 158.32%), respectively. The LRRs of recipients at 0.5, 1, 3, and 6 months were 58.49%±26.67% (49.04%, 67.95%), 50.16%±27.25% (40.94%, 59.38%), 44.36%±26.75% (35.30%, 53.41%), and 31.19%±22.57% (20.91%, 41.47%), respectively. The former values were higher than the latter. The LRRs of recipients with the MHV was higher than those without MHV at 1 and 3 months (P<0.05). The LRRs at 1 month were 59.63%±27.48% and 41.68%±24.73%, and at 3 months were 57.25%±25.42% and 32.81%±22.79%, respectively. The IRLV/ESLV and IGV/ESLV were negatively correlated with LRRs at several times [r=-0.419 (-0.646, -0.134), -0.608 (-0.832, -0.318), respectively; P<0.05]. At 0.5 month, significant difference was found between Child-Pugh score of ≤9.55 and >9.55 (P<0.05) and MELD score of ≤14 and >14 (P<0.05). After LDLT, donors had more significant and faster liver regeneration than the recipients. Graft with or without MHV, initial liver volume, and preoperative liver function status of the recipients significantly affect liver regeneration.

Applications of neural networks in liver transplantation

The use of neural networks as a cutting-edge technique in the medical field has drawn considerable attention. Neural network models “learn” from a large amount of data and then find corresponding clinical patterns that are challenging for clinicians to recognize. In this study, we focus on liver transplantation, which is an effective treatment for end-stage liver diseases. The management before and after liver transplantation produces a massive quantity of medical data, which can be fully processed by neural networks. We describe recent progress in the clinical application of neural networks to liver transplantation in five respects: pre-transplantation evaluation of the donor and recipient , recipient outcome prediction, allocation system development, operation monitoring, and post-transplantation complication prediction . This review provides clinicians and researchers with a description of forefront applications of neural networks in the field of liver transplantation and discusses prospects and pitfalls.

Are MELD and MELDNa Still Reliable Tools to Predict Mortality on the Liver Transplant Waiting List?

Liver transplantation is the only curative treatment for end-stage liver disease. Unfortunately, the scarcity of donor organs and the increasing pool of potential recipients limit access to this life-saving procedure. Allocation should account for medical and ethical factors, ensuring equal access to transplantation regardless of recipient's gender, race, religion, or income. Based on their short-term prognosis prediction, model for end-stage liver disease (MELD) and MELD sodium (MELDNa) have been widely used to prioritize patients on the waiting list for liver transplantation resulting in a significant decrease in waiting list mortality/removal. Recent concern has been raised regarding the prognostic accuracy of MELD and MELDNa due, in part, to changes in recipients' profile such as body mass index, comorbidities, and general condition, including nutritional status and cause of liver disease, among others. This review aims to provide a comprehensive view of the current state of MELD and MELDNa advantages and limitations and promising alternatives. Finally, it will explore future options to increase the donor pool and improve donor-recipient matching.

INNATE IMMUNE CELLSIN IMMUNE TOLERANCE AFTER LIVER TRANSPLANTATION

Currently, liver transplantation is the most effective treatment for end-stage liver disease. Immuno-suppressive agents are required to be taken after the operations, which have significantly reduced rejection rates and improved the short-term (&lt;1 year) survival rates. However, post-transplant complications related to the immuno-suppressive therapy have led to the development of new protocols aimed at protecting renal function and preventing de novo cancer and dysmetabolic syndrome. Donor specific immune tolerance, which means the mature immune systems of recipients will not attack the grafts under the conditions without any immunosuppression therapies, is considered the optimal state after liver transplantation. There have been studies that have shown that some patients can reach this immune tolerance state after liver transplantation. The intrahepatic immune system is quite different from that in other solid organs, especially the innate immune system. It contains a variety of liver specific cells, such as liver-derived dendritic cells, Kupffer cells, liver sinusoidal endothelial cells, liver-derived natural killer (NK) cells, natural killer T (NKT) cells, and so on. Depending on their specific structures and functions, these intrahepatic innate immune cells play important roles in the development of intrahepatic immune tolerance. In this article, in order to have a deeper understanding of the tolerogenic functions of liver, we summarized the molecular mechanisms of immune tolerance induced by intrahepatic innate immune cells after liver transplantation.

The fundamentals of sex-based disparity in liver transplantation: Understanding can lead to change.

Liver transplantation (LT) is the definitive treatment for end-stage liver disease. Unfortunately, women are disadvantaged at every stage of the LT process. We conducted a literature review to increase the understanding of this disparity. Hormonal differences, psychological factors, and Model for End-Stage Liver Disease (MELD) score inequalities are some pretransplantation factors that contribute to this disparity. In the posttransplantation setting, women have differing risk than men in most major outcomes (perioperative complications, rejection, long-term renal dysfunction, and malignancy) and assessing the two groups together is disadvantageous. Herein, we propose interventions including standardized criteria for LT referral, using an alternate MELD, education for support of women, and motivating women to seek living donors. Understanding sex-based differences will allow us to improve access, tailor management, and improve overall outcomes for all patients, particularly women.

The Potential Clinical Use of Stem/Progenitor Cells and Organoids in Liver Diseases.

The liver represents the most important metabolic organ of the human body. It is evident that an imbalance of liver function can lead to several pathological conditions, known as liver failure. Orthotropic liver transplantation (OLT) is currently the most effective and established treatment for end-stage liver diseases and acute liver failure (ALF). Due to several limitations, stem-cell-based therapies are currently being developed as alternative solutions. Stem cells or progenitor cells derived from various sources have emerged as an alternative source of hepatic regeneration. Therefore, hematopoietic stem cells (HSCs), mesenchymal stromal cells (MSCs), endothelial progenitor cells (EPCs), embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are also known to differentiate into hepatocyte-like cells (HPLCs) and liver progenitor cells (LPCs) that can be used in preclinical or clinical studies of liver disease. Furthermore, these cells have been shown to be effective in the development of liver organoids that can be used for disease modeling, drug testing and regenerative medicine. In this review, we aim to discuss the characteristics of stem-cell-based therapies for liver diseases and present the current status and future prospects of using HLCs, LPCs or liver organoids in clinical trials.

Expert consensus on diagnosis and treatment of end-stage liver disease complicated infection (2021 version)

End-stage liver disease (ESLD) is a life-threatening clinical syndrome with significantly increased mortality when the patients are complicated with infections. For patients with ESLD, infections can induce or aggravate the liver decompensation. In turn, infections are among the most common complication with the disease progression. Experts from Society of Infectious Diseases, Chinese Medical Association firstly formulated "Expert Consensus on Diagnosis and Treatment of End-Stage Liver Disease Complicated with Infection" in July 2018, which is extensively revised based on clinical evidence of recent three years. This consensus summarizes the up-to-date knowledge and experiences across Chinese colleagues, intending to provide principles and wording procedures for clinicians to diagnose and treat ESLD patient complicated with infections.

Expert consensus on diagnosis and treatment of end-stage liver disease complicated with infections（2021 version）

Expert consensus on diagnosis and treatment of end-stage liver disease complicated with infections（2021 version）

Reprogramming the spleen into a functioning ‘liver’ in vivo

ObjectiveLiver regeneration remains one of the biggest clinical challenges. Here, we aim to transform the spleen into a liver-like organ via directly reprogramming the splenic fibroblasts into hepatocytes in vivo.DesignIn...

EVALUATION OF THE HEPATOPROTECTOR EFFECT OF A SUPPLEMENT WITH CURCUMA LONGA AGAINST REPERFUSION ISCHEMIA DAMAGE IN AN EXPERIMENTAL MODEL IN WISTAR RATS

Liver transplantation (LT) is the treatment for end-stage liver disease that may present graft rejection. Conditioning with natural products has shown great therapeutic utility, specifically against ischemia-reperfusion (IR). Curcumin has shown protective activity, which is why it is proposed to evaluate whether curcumin (AGROVITAE-UANL) reduces IR liver damage. For thin layer chromatography, curcumin was started in 0.1% methanol using Si-60GF254 silica gel and chloroform: methanol (95: 5). To verify the presence of 3 curcuminoids, delay factors (Rf) equal to the curcumin standard (Sigma-Aldrich) were detected. For the 70% partial IR liver damage model, a midline laparotomy (L) was performed, the liver was dissected, the hepatic hilum clamped for 1 hour of IR and subsequent sacrificed by exsanguination. 4 groups were established: Sham (3% Tween 20; 500 µL x 3 days; L); IR (3% Tween 20; 500 µL x 3 days; L + IR); SIGMA + IR (3% Tween 20; curcumin 200 mg / kg x 3 days; L + IR); AGROVITAE+IR (3% Tween 20; curcumin 200 mg / kg x 3 days; L+IR). ALT, AST, LDH, FA, BIL, PT, ALB, MDA and Total Antioxidants (AOT) were quantified by UV-Vis. NF-kβ and MPO were evaluated by RT-qPCR. The protocol approved by the ethics committee with registration PI20-00002. The Rf of 3 curcuminoids was calculated: Curcumin (0.80), Demethoxycurcumin (0.69) and Bisdemethoxycurcumin (0.62). In the damage model, a significant increase in ALT, AST and LDH was achieved and a hepatoprotective effect against IR damage due to decreases in liver enzymes (Figure), there was no change in the rest of the markers. No significant difference was found in the oxidative stress markers MDA and AOT and in the gene expression of NF-kβ and MPO associated with IR. Reyes et. al (2014) reported the presence of the 3 curcuminoids and their Rf, which agrees with our results. Wang et al. (2017) reported a decrease in ALT and AST values ​​in the groups treated with curcumin in a partial IR model, which is consistent with this study. Lintz et al. (2017) reported in a partial IR model that LDH may not be affected, this contrasts with our results; however, in the curcumin groups, no significant difference was observed against IR. Zabala et al. (2019) reported elevation of ALT and AST that agrees with what was obtained in this study. Tinsay et al. (2014) reported that in IR, there was no effect on synthesis and cholestasis markers, as in this study, this can be explained because the damage produced is cell lysis. Regarding the non-difference in the gene expression of NF-kβ and MPO, other authors reported that the regulation of inflammatory response genes would have an effect at longer reperfusion times (3, 6, 12 and 24h), in hepatic partial IR models. The presence of the 3 curcuminoids was confirmed in AGROVITAE-UANL. The IR damage model was effective in increasing ALT, AST, and LDH. A hepatoprotective effect of AGROVITAE-UANL, against IR by decreasing ALT and AST. No effect was observed on liver synthesis markers or cholestasis, so the damage was only associated with cell lysis. There was also no effect on MDA, AOT markers and inflammatory response genes at the established IR times, ruling out these pathways as possible mechanisms of action. The authors declare that there is no conflict of interest. Funded by PAICYT-UANL-SA1458-20.

Cell reprogramming in liver with potential clinical correlations.

The theory of cell reprogramming has developed rapidly during the past decades. Cell reprogramming has been widely used in the construction of experimental models and cytotherapy for certain diseases. Hepatocyte-like cells that are important for the treatment of end-stage liver disease can now be obtained with a variety of reprogramming techniques. However, improving the differentiation status and physiological function of these cells remains challenging. Hepatocytes can transdifferentiate into other types of cells directly, whereas other types of cells can also transdifferentiate into hepatocyte-like cells both in vitro and in vivo. Moreover, cell reprogramming is to some extent similar to malignant cell transformation. During the initiation and progression of liver cancer, cell reprogramming is always associated with cancer metastasis and chemoresistance. In this review, we summarized the research related to cell reprogramming in liver and highlighted the potential effects of cell reprogramming in the pathogenesis and treatment of liver diseases.

Liver transplantation in the Intensive Care Unit: twenty years experience in a center medium income on Peru

Liver transplantation is the major treatment for end-stage liver disease. Postoperative care is a great challenge to reduce morbidity and mortality in patients. In this sense, management in the liver ICU allows hemodynamic management, coagulation monitoring, renal support, electrolyte disturbances, respiratory support and early weaning from mechanical ventilation and evaluation of the liver graft. Objective: The present study shows the results of the management of liver transplant patients in 20 years of experience in a transplant center in a low- to middle-income country. Materials and methods: The medical records of 273 adult patients in the ICU in the immediate postoperative liver transplant were reviewed, from March 20, 2000 to November 30, 2020, including the effect of the pandemic caused by COVID-19. Liver-kidney, retransplanted, SPLIT, and domino transplant patients were excluded. Results: The most frequent etiology for LTx was NASH (35%), the mean age was 49 years, MELD Score ranged 15 - 20 (47.5%), 21 - 30 (46%) &gt; 30 (6.2%). ICU pre transplant stay 7%, average ICU stay: 7.8 days. APACHE average admission: 14.9 points. Weaning extubation of 91.8% patients in ICU and Fast Track in 8.2%. The most frequent respiratory complication was atelectasis 56.3%, pneumonia (31.3%); AKI 1 (60.9%), and 11.1% with hemodyalisis support (AKI3). Immunosuppression: Tacrolimus (8.9%). Post-operative ICU mortality was 6.2%. Conclusions: The management of liver transplantation in the ICU is essential to achieve optimal results in patients who present advanced liver disease and require advanced life support in the immediate postoperative period and thus optimize graft survival.

Current understanding of mesenchymal stem cells in liver diseases.

Liver diseases caused by various factors have become a significant threat to public health worldwide. Liver transplantation has been considered as the only effective treatment for end-stage liver diseases; however, it is limited by the shortage of donor organs, postoperative complications, long-term immunosuppression, and high cost of treatment. Thus, it is not available for all patients. Recently, mesenchymal stem cells (MSCs) transplantation has been extensively explored for repairing hepatic injury in various liver diseases. MSCs are multipotent adult progenitor cells originated from the embryonic mesoderm, and can be found in mesenchymal tissues including the bone marrow, umbilical cord blood, adipose tissue, liver, lung, and others. Although the precise mechanisms of MSC transplantation remain mysterious, MSCs have been demonstrated to be able to prevent the progression of liver injury and improve liver function. MSCs can self-renew by dividing, migrating to injury sites and differentiating into multiple cell types including hepatocytes. Additionally, MSCs have immune-modulatory properties and release paracrine soluble factors. Indeed, the safety and effectiveness of MSC therapy for liver diseases have been demonstrated in animals. However, pre-clinical and clinical trials are largely required to confirm its safety and efficacy before large scale clinical application. In this review, we will explore the molecular mechanisms underlying therapeutic effects of MSCs on liver diseases. We also summarize clinical advances in MSC-based therapies.

A meta-analysis on the incidence of donor-related depression after liver transplant.

Living donor liver transplantation (LDLT) is increasing, yet gaps exist in the understanding of psychological wellbeing of donors after liver transplant. This meta-analysis seeks to evaluate the incidence and risk factors for donor-related depression after liver transplantation. A search was conducted on Medline and Embase database. Articles assessing incidence of depression in LDLT donors were included. Incidence was pooled after Freeman-Turkey double-arcsine transformation. For risk factors, dichotomous variables were analyzed with generalized linear model, while a conventional meta regression with logit transformation was conducted for continuous variables. Of 1069 abstracts, 40 articles underwent full-text review. Seventeen articles were included. The pooled incidence of depression among 1888 LT donors was 7.66% (CI: 4.47-12.80%). Depression rates were significantly higher in Asian compared to Western studies (RR: 1.73, CI: 1.19-2.52, P = 0.0039). Female gender (P < 0.001), Caucasian ethnicity (P = 0.047), employment status (P < 0.001) and lower education levels (P = 0.044) were significantly associated with depression. Donor relationship with recipients was not a significant risk factor. LDLT remains a core aspect of the treatment of end-stage liver disease. However, the high depression rates after LT suggest that there remains room for improvement in the care of donors' mental health post-transplant.

Moving Forward to New Trends in Liver Transplantation

Liver transplantation (LT) is the only recognized effective treatment for end-stage liver disease (ESLD) and acute fulminant liver failure [...]

Using Infodemiology Metrics to Assess Public Interest in Liver Transplantation: Google Trends Analysis.

BackgroundLiver transplantation (LT) is the only curative treatment for end-stage liver disease. Less than 10% of global transplantation needs are met worldwide, and the need for LT is still increasing. The death rates on the waiting list remain too high.ObjectiveIt is, therefore, critical to raise awareness among the public and health care providers and in turn increasingly acquire donors.MethodsWe performed a Google Trends search using the search terms liver transplantation and liver transplant on October 15, 2020. On the basis of the resulting monthly data, the annual average Google Trends indices were calculated for the years 2004 to 2018. We not only investigated the trend worldwide but also used data from the United Network for Organ Sharing (UNOS), Spain, and Eurotransplant. Using pairwise Spearman correlations, Google Trends indices were examined over time and compared with the total number of liver transplants retrieved from the respective official websites of UNOS, the Organización Nacional de Trasplantes, and Eurotransplant.ResultsFrom 2004 to 2018, there was a significant decrease in the worldwide Google Trends index from 78.2 in 2004 to 20.5 in 2018 (–71.2%). This trend was more evident in UNOS than in the Eurotransplant group. In the same period, the number of transplanted livers increased worldwide. The waiting list mortality rate was 31% for Eurotransplant and 29% for UNOS. However, in Spain, where there are excellent awareness programs, the Google Trends index remained stable over the years with comparable, increasing LT numbers but a significantly lower waiting list mortality (15%).ConclusionsPublic awareness in LT has decreased significantly over the past two decades. Therefore, novel awareness programs should be initialized.

Mitochondrial Targeting Therapy Role in Liver Transplant Preservation Lines: Mechanism and Therapeutic Strategies.

The normal function of mitochondria in the hepatic parenchyma can be disrupted by ischemia/reperfusion (I/R) damage during liver transplantation. The pathology of these insults involves various cellular and molecular steps of events that have been extensively researched over decades but are yet to provide complete answers. This review discusses the brief mechanism of the pathophysiology following ischemia/reperfusion injury (IRI) and various targeting strategies that could result in improved graft function.The traditional treatment for end-stage liver disease i.e., liver transplantation, has been complicated by I/R damage. The poor graft function or primary non-function found after liver transplantation may be due to mitochondrial dysfunction following IRI. As a result, determining the sequence of incidents that cause human hepatic mitochondrial dysfunction is crucial; it might contribute to further improvements in the outcome of liver transplantation. Early discovery of novel prognostic factors involved in IRI could serve as a primary endpoint for predicting the outcome of liver grafts as well as promoting the early implementation of novel IRI-prevention strategies. In this review, recent developments in the study of mitochondrial dysfunction and I/R damage are discussed, specifically those concerning liver transplantation. Furthermore, we also explore different pharmacological therapeutic methods that may be used and their connections to mitochondrion-related processes and goals.Although significant progress has been made in our understanding of IRI and mitochondrial dysfunction, further research is needed to elucidate the cellular and molecular pathways underlying these processes to help identify biomarkers that can aid donor organ evaluation.