Post-transplant Mortality Research Articles

Echocardiographic evaluation in patient candidate for liver transplant: from pathophysiology to hemodynamic optimization.

Cardiovascular complications are common in patients with severe liver disease and are an important cause of peri-operative and post-transplant morbidity and mortality. Cirrhotic cardiomyopathy (CCM), often found in advanced liver disease, is characterized by diastolic dysfunction, systolic dysfunction, and electrophysiological abnormalities. While CCM may not cause symptoms at rest, it can become evident during stressful activities, such as surgery. Liver transplantation, while being the definitive treatment for end-stage liver disease (ESLD), carries significant cardiovascular risks. Preoperative cardiac evaluation is essential for assessing these risks and planning appropriate management. Cardiac imaging, particularly echocardiography, plays a crucial role in evaluating liver transplant candidates, helping to identify conditions such as CCM, pulmonary hypertension, hepatopulmonary syndrome, and others. Currently, liver transplant anesthetists must acquire echocardiographic knowledge and skills to evaluate the cardiocirculatory conditions of the transplanted patient, especially in the pre-operative phase, but also intra-operatively and post-operatively.

The impact of recipient hypernatremia on pediatric liver transplantation outcomes.

In pediatric liver transplants, dysnatremias have been found to have an impact on pre- and post-transplant outcomes. However, much of the current literature has focused on wait-list survival, secondary organ damage, and dysnatremia in donors rather than in recipients. To understand the effect of recipient immediate pre-transplant hypernatremia on post-transplant mortality, we conducted a multivariable retrospective review analyzing data from 8,011 pediatric patients undergoing liver transplantation provided by the United Network for Organ Sharing (UNOS). Multivariable analysis of hypernatremia showed an increased risk of mortality (odds ratio [OR]: 2.49, 95% confidence interval [CI]: 1.75, 3.54 for a serum sodium between 150-155mEq/L) while hyponatremia did not show a significant increase in relative risk for mortality (HR: 1.11, 95% CI: 0.75, 1.63 for a serum sodium between 125-130mEq/L). Kaplan-Meier (KM) curves stratified by sodium level showed statistically significant differences in outcomes with progressively increasing mortality associated with increasing serum sodium levels. In particular, there is a statistically significant increase in 90-day mortality with serum sodium levels above 150mEq/L. Hyponatremia had a moderate impact on mortality but was not statistically significant. Our analysis of immediate pre-transplantation resolution of hypernatremia also showed improved survival outcomes with a decreased mortality compared to transplant patients with unresolved hypernatremia. In conclusion, immediate pre-transplant recipient hypernatremia has a substantial impact on pediatric post-liver transplantation survival. Corrected hypernatremia resulted in decreased mortality compared to uncorrected hypernatremia. Recipient hypernatremia is an important indicator of disease processes and a predictor of poor post-transplantation mortality outcomes.

Donor age and ischemic time in heart transplantation –implications for organ preservation

IntroductionThe Organ Care System and Non-ischemic Heart Preservation methods have emerged as significant advancements in heart transplantation, designed to mitigate ischemic injury and extend preservation times. However, their high costs and logistical complexities necessitate strategic utilization. MethodsWe evaluated data from 83,761 heart transplants registered in the International Society for Heart and Lung Transplantation registry from 1988 to 2018. Utilizing a Cox proportional hazards model, we explored the influence of donor age and ischemic time on transplant survival. A key innovation of our study is the development of a nomogram to predict post-transplant survival, incorporating both traditional and advanced statistical methods. ResultsThe median age of recipients was 52 years (22% female) and 33 years (31% female) for donors. Analysis revealed a median ischemic time of 3 hours and median survival of 11.5 years across the cohort. The nomogram showed a decline in survival probabilities with increasing donor age, notably from age 40 and more significantly with ischemic times >4 hours. Ischemic times ≥4 hours versus <2 hours were associated with hazard ratio (HR) of 1.2 (95% CI, 1.1-1.3) for donors aged 40-59, a disparity that escalated for donors aged ≥60 (HR: 2.0; 95% CI, 1.5-2.7). ConclusionThis study highlights the importance of careful donor selection and indicates that certain groups, particularly older donors with prolonged ischemic times, might benefit from ex-vivo preservation techniques. The developed nomogram offers a practical tool for clinicians, enhancing decision-making by providing detailed insights into the relationship between donor age, ischemic time, and post-transplant mortality.

Impact of Heart Transplant Allocation Change on Waitlist Mortality and Posttransplant Mortality in Patients With Left Ventricular Assist Devices.

In October 2018, the US heart transplant (HT) allocation system was revised giving patients with left ventricular assist device (LVAD) intermediate priority status. Few studies have examined the impact of this policy change on outcomes among patients with LVAD. We sought to determine how the allocation change impacted waitlist and posttransplant mortality in patients with LVAD. We retrospectively assessed the United Network for Organ Sharing registry for patients with LVAD who were listed for or underwent HT between October 2016 and October 2021. We evaluated waitlist mortality using competing risks analysis and a multivariable Fine-Gray model, and posttransplant mortality using Kaplan-Meier survival analysis and a multivariate proportional hazards model. We analyzed data from 3835 patients with LVAD listed for HT and 3486 patients with LVAD who underwent HT during the study period. Listing for HT preallocation change was significantly associated with an increased risk of waitlist mortality (Gray P=0.0058) compared with postallocation change. After adjustment for covariates, mortality differences by listing era were attenuated, but LVAD brand was significantly associated with waitlist mortality (HM3 versus HMII; hazard ratio, 0.38 [95% CI, 0.21-0.69]; P=0.002; HVAD versus HMII; hazard ratio, 0.79 [95% CI, 0.48-1.30]; P=0.36; overall P=0.004). In contrast, HT postallocation change was associated with increased posttransplant mortality (log-rank P=0.0172) compared with preallocation change. In a multivariable analysis, the association with posttransplant mortality between transplant eras was attenuated, but ischemic time (hazard ratio, 1.16 [95% CI, 1.07-1.26]; P<0.001) and status at time of HT (Status 1-3 versus 4; hazard ratio, 1.29 [95% CI, 1.04-1.61]; P=0.02) were significantly associated with posttransplant mortality. Among patients with LVAD, lower waitlist mortality postallocation change was likely driven by improved LVAD technology. Higher posttransplant mortality following the allocation change was largely attributable to longer ischemic times and patient acuity.

Pre-transplant Serum Procalcitonin as a Predictor of Early Post-transplant Sepsis and Mortality After Living Donor Liver Transplantation: A Prospective Observational Study.

The early post-transplant period after liver transplantation is critical, as recipients are highly susceptible to sepsis due to their immune-compromised state. This study aimed to identify the association between preoperative procalcitonin and early post-transplant sepsis and mortality at one month after living donor liver transplantation (LDLT). Allpatients who underwent LDLT from July 2021 to December 2021 were recruited prospectively. Participants were divided into two groups based on preoperative PCT levels: elevated (>0.5 ng/ml) and low levels (<0.5 ng/ml). Serum procalcitonin (PCT) levels were measured on the day of transplant and on postoperative days 3 and 7. The relationship between preoperative PCT and post-transplant sepsis was evaluated using a Chi-square test, and receiver operating characteristic (ROC) curves were generated. Sepsis occurred in 48.3% of patients, with a significant association between elevated preoperative PCT levels and early post-transplant sepsis (p=0.023). The ROC curve for preoperative PCT showed moderate predictive ability (area under curve (AUC)=0.664), while PCT levels on postoperative day 3 demonstrated better discriminatory power (AUC=0.790). PCT levels measured on day 7 also had good diagnostic accuracy, with an AUC of 0.843 and a significant difference between the sepsis and non-sepsis groups (p=0.002). The length of ICU stay was significantly longer in the sepsis group (p=0.009). Conclusion: Elevated preoperative PCT levels can predict early post-transplant sepsis in LDLT patients. PCT monitoring may enhance risk stratification and guide perioperative management, improving post-transplant outcomes.

Robust Predictive Performance of the SALT-M Score for Clinical Outcomes in Asian Patients With Acute-on-Chronic Liver Failure.

Acute-on-chronic liver failure (ACLF) is a syndrome of patients with chronic liver disease presenting with multiple organ failures. Recently, Sundaram-ACLF-LT Mortality (SALT-M) score has been developed to predict 1-year post-liver transplantation mortality. We validated the SALT-M score in a large-volume, Asian single-centre cohort. We validated the SALT-M score in a large-volume, Asian single-centre cohort. We analysed 224 patients of ACLF grade 2-3. Area under the receiver operating characteristic curve (AUROC) and concordance index (c-index) were used to assess and compare the predictability of posttransplant mortality of SALT-M and other scores. Moreover, we compared the survivals of patients with high and low SALT-M, in conjunction with MELD score and ACLF grade. The AUROC for prediction of 1-year post-LT survival was higher in SALT-M (0.691) than in MELD, MELD-Na, MELD 3.0 and delta-MELD. Similarly, the c-index of the SALT-M (0.650) was higher than aforementioned MELD systems. When categorised by the cut-off of SALT-M ≥ 20 and MELD ≥ 30, patients with high SALT-M exhibited lower post-LT survival than those with low SALT-M scores regardless of high or low MELD (40.0% for high SALT-M/high MELD vs. 42.9% for high SALT-M/low MELD vs. 73.8% for low SALT-M/high MELD vs. 63.7% for low SALT-M/low MELD, p < 0.001). In patients with ACLF grade 3, SALT-M effectively stratified the posttransplant mortality (39.4% for high SALT-M vs. 63.1% for low SALT-M, p = 0.018). SALT-M outperformed previous MELD systems for predicting posttransplant mortality in Asian LT cohort with severe ACLF. Transplantability for patients with severe ACLF could be determined based on SALT-M.

Viral Infections in Pediatric Kidney Transplant Recipients: Effects on Graft Function, Risk Factors, and Patient Outcomes.

Viral infections are the leading cause of posttransplant morbidity and mortality. We aimed to determine the effect on graft function, the risk factors, the frequency, and types of viral infections and to evaluate the effect of viral infections on kidney and patient outcomes in pediatric kidney transplant patients. Records of children undergoing kidney transplant in our center during the period February 1, 2010, to December 31, 2023, were retrospectively evaluated. Demographic and laboratory data, kidney failure etiologies, donor types, immunosuppression treatments, acute rejection episodes, accompanying viral infections, glomerular filtration rate, and graft loss rate were analyzed. Seventy-nine pediatric kidney transplant recipients were included in the study. The number of patients who experienced viral infections was 18 (23%). In total, 25 infection episodes were identified, with 6 (24%) attributed to cytomegalovirus infection, 8 (32%) to BK virus infection, 6 (24%) to varicella zoster virus infection (4 cases of shingles, 2 cases of chickenpox), 4 (16%) to parvovirus B19 infection, and 2 (8%) to COVID-19. Of 25 infection episodes, rejection episodes were observed in 11 cases (44%), and infections manifested after rejection in 8 cases (32%). Viral infections occurred an average of 15 months after rejection episodes. For 15 (60%) of the 25 infection episodes, the glomerular filtration rate was observed to be <60 mL/min/1.73 m2 during viral infection. Two patients succumbed to viral infections; 1 was due to COVID-19, and 1 was due to coinfection with parvovirus B19 and cytomegalovirus. Our data emphasized the significant effect of viral infections on pediatric kidney transplant recipients. Early diagnosis and treatment in kidney transplant recipients are important, and clinicians should be alert.

A Retrospective View of Post Renal Transplant Urinary Tract Infections: An Experience of A UK Transplant Centre

Urinary tract infections (UTIs) are prevalent post renal transplant complication. These infections are most common in renal transplant recipient’s contrary to their incidence in general healthy population as shown by previous studies. Though the frequencies of occurrences are different in renal transplant patients. There is general lack of consensus on the risk factors associated with development of UTIs in renal transplant patients as well as effects posed by them and occurrence of mortality in patient group. This retrospective cohort study investigated and included adults’ patients who were operated for renal transplant in a single transplant center in UK from Jan 2014 to December 2023. The number of patients were 604 with two hundred and fifty-nine developed one or more UTIs in 42 months follow-up period. Significant risk factors for post-transplant UTIs were advanced age, female gender, reflux kidney disease, use of azathioprine and cadaveric donor. UTIs did not increase risk for renal graft loss, but were associated with increased mortality (3.5 odds ratio, 95% confidence interval 1.68–7.23). We conclude UTIs may be associated with an increased mortality risk in renal transplant recipients. Prevention of UTIs in high-risk renal transplant patients or those with recurrent UTIs may possibly decrease post-transplant mortality.

Pretransplant cardiac stress testing and transplant wait time in kidney transplantation candidates

ObjectiveRoutine screening for cardiovascular disease before kidney transplantation remains controversial. This study aims to compare cardiac testing rates in patients with end-stage renal disease, referred and not referred for transplantation,...

Analysis of the waitlist performance and post-transplant outcomes of lung transplant in elderly recipients in Korea: A nationwide cohort study.

There is a lack of information on the waitlist performance and post-transplant outcomes of lung transplants in elderly recipients in Korea. We retrospectively reviewed and analyzed data from the Korean Network for Organ Sharing database between March 2010 and August 2023. In total, 2574 patients were listed for lung transplantation during the study period, with 511 (19.9%) of them being over 65 years of age. Among these, 188 patients (36.8%) underwent transplantation, while 184 patients (36%) passed away without undergoing transplantation at the time of data extraction. The most prevalent underlying disease on the waitlist was idiopathic pulmonary fibrosis, accounting for 68.1%. The 1-year survival rate was significantly lower in the elderly compared to that in the nonelderly (65.4vs. 75.4%; p=.004). In the multivariate Cox analysis, elderly (hazard ratio [HR], 1.49; 95% CI, 1.14-1.97; p=.004) and a high urgent status at registration (HR, 1.83; 95% CI, 1.40-2.40; p<.001) were significantly associated with post-transplant 1-year mortality. Kaplan-Meier curves demonstrated a significant difference in post-transplant mortality based on the urgency status at enrollment (χ2=8.302, p=.016). Even with the same highly urgent condition at the time of transplantation, different prognoses were observed depending on the condition at listing (χ2=9.056, p=.029). The elderly exhibited worse transplant outcomes than nonelderly adults, with a highly urgent status at registration identified as a significant risk factor. Unprepared, highly urgent transplantation was associated with poor outcomes.

Association of Pre–Lung Transplant Opioid Use With Posttransplant Opioid Use and Outcomes

BackgroundPreoperative opioid use (OU) is a strong risk factor for poor postoperative outcomes in other surgical populations but has not been explored in lung transplant (LT) recipients nationally. MethodsThe study identified adult (aged ≥18 years) US lung transplant (LT) recipients from 2011 to 2021 in the Scientific Registry of Transplant Recipients with prescription data through a pharmacy data set. Posttransplantation ventilatory support, infection, and mortality by pretransplantation OU (prescription fill ≤6 months before transplantation) were compared using multivariable regression. ResultsAmong 17,285 LT recipients, 17.9% had pretransplantation OU. The odds of posttransplantation opioid prescription fill were 3.18-fold higher 0 to 6 months after transplantation (adjusted odds ratio [aOR], 3.18; 95% CI, 2.91-3.47; P < .001) and 14.29-fold higher 6 to 12 months after transplantation (aOR, 14.29; 95% CI, 12.61-16.19; P < .001) among LT recipients with vs without pretransplantation OU. Pretransplantation OU was associated with 16% higher posttransplantation mortality (adjusted hazard ratio, 1.16; 95% CI, 1.09-1.25; P < .001) and a higher risk of ventilator use >48 hours (aOR, 1.14; 95% CI, 1.04-1.25; P = .006). ConclusionsPretransplantation OU was the strongest independent risk factor for posttransplantation OU and was associated with greater morbidity and mortality. Reducing pretransplantation and posttransplantation OU could benefit LT recipients and should be explored.

Long-term outcomes and risk factors for early bacterial infection after pediatric liver transplantation: a prospective cohort study.

Liver transplantation (LT) is the most efficient treatment for pediatric patients with end-stage liver diseases, while bacterial infection is the leading reason for post-transplant mortality. The present study is to explore the outcomes and risk factors of early bacterial infection (within 1 months) after pediatric LT. In this prospective cohort study, 1316 pediatric recipients [median (IQR) age: 9.1 (6.3-28.0) months; male: 48.0%; median (IQR) follow-up time: 40.6 (29.1-51.4) months] who received LT from September 2018 to April 2022 were included. Bacterial culture samples such as sputum, abdominal drainage, blood, and so on were collected when recipients were presented with infective symptoms. Kaplan-Meier analysis was applied to estimate the long-term survival rates and logistic regression was used to identify independent risk factors. To explore the role of pretransplant rectal swab culture (RSC) in reducing post-transplant bacterial infection rate, 188 infant LT recipients [median (IQR) age: 6.8 (5.5-8.1) months; male: 50.5%] from May 2022 to September 2023 were included. Log-binomial regression was used to measure the association of pretransplant RSC screening and post-transplant bacterial infection. The 'Expectation Maximization' algorithm was used to impute the missing data. Bacterial infection was the primary cause for early (38.9%) and overall mortality (35.6%) after pediatric LT. Kaplan-Meier analysis revealed inferior 1-year and 5-year survival rates for recipients with post-transplant bacterial infection (92.6 vs. 97.1%, 91.8 vs. 96.4%, respectively; P <0.001). Among all detected bacteria, Staphylococcus spp. (34.3%) and methicillin-resistant coagulase-negative Staphylococci (43.2%) were the dominant species and multidrug resistant organisms, respectively. Multivariable analysis revealed that infant recipients [adjusted odds ratio (aOR) 1.49; 95% CI: 1.01-2.20], male recipients (aOR, 1.43; 95% CI: 1.08-1.89), high graft-to-recipient weight ratio (aOR, 1.64; 95% CI: 1.17-2.30), positive post-transplant RSC (aOR, 1.45; 95% CI: 1.04-2.02) and nasopharyngeal swab culture (aOR 2.46; 95% CI: 1.72-3.52) were independent risk factors for early bacterial infection. Furthermore, RSC screening and antibiotic prophylaxis before transplantation could result in a relatively lower post-transplant infection rate, albeit without statistical significance (adjusted RR, 0.53; 95% CI: 0.25-1.16). In this cohort study, post-transplant bacterial infection resulted in an inferior long-term patient survival rate. The five identified independent risk factors for post-transplant bacterial infection could guide the prophylaxis strategy of post-transplant bacterial infection in the future. Additionally, pretransplant RSC might decrease post-transplant bacterial infection rate.

Report on post-transplantation cancer in southeast Asia from the Thai kidney transplantation cohort

Post-transplantation cancer is a significant cause of mortality among kidney transplant recipients (KTR). The incidence of post-transplantation cancer varies based on geographic region and ethnicity. However, data on KTR from South East Asia, where characteristics differ from other parts of Asia, is lacking. We conducted a retrospective cohort study at a transplant center in Thailand to investigate the incidence of post-transplantation cancer and mortality rates. Factors associated with post-transplantation cancer and patient outcomes were analyzed using competing-risks regression. The study included 1156 KTR with a post-transplant follow-up duration of 5.1 (2.7–9.4) years. The age- and sex-adjusted incidence rate of post-transplant cancer was highest for urothelial cancer (6.9 per 1000 person-years), which also resulted in the highest standardized incidence ratio (SIR) of 42.5 when compared to the general population. Kidney cancer had the second-highest SIR of 24.4. Increasing age was the factor associated with an increased risk of post-transplant cancer (SHR 1.03; 95% CI 1.01–1.05). Human leukocyte antigen (HLA) DR mismatch was associated with a decreased risk of post-transplant cancer (SHR 0.72; 95% CI 0.52–0.98). Post-transplantation cancer was significantly associated with patient mortality (HR 3.16; 95% CI 2.21–4.52). Cancer significantly contributes to KTR mortality, and the risk profile for cancer development in Thai KTRs differs from that of Western and most Asian counterparts. Further research is essential to explore appropriate screening protocols for countries with high rates of urothelial and kidney cancer, including Thailand.

Integrating risks and benefits: pretransplant assessment and patient selection for heart transplantation in adult congenital heart disease.

The number of adult congenital heart disease (ACHD) patients presenting for consideration of heart transplantation continues to grow. Comprehensive pretransplant assessment and thoughtful patient selection are of critical importance to mitigate perioperative and posttransplant morbidity and mortality in this population. There is increasing evidence that patient outcomes after the onset of heart failure in the ACHD population are poor while overall transplant outcomes for ACHD patients have improved over time. Delineation of factors associated with better versus worse posttransplant outcomes is an area of ongoing research. Several studies have found that delayed patient referral, anatomic complexity and the presence of noncardiac organ dysfunction may increase peri-transplant and posttransplant risk. Pretransplant assessment and patient selection in ACHD patients should focus on mitigating perioperative and early posttransplant risk. Anatomic complexity, noncardiac organ dysfunction, and referral timing after the onset of heart failure can contribute to poor posttransplant outcomes and should inform patient selection.

Impact of CT-relevant skeletal muscle parameters on post-liver transplantation survival in patients with hepatocellular carcinoma.

The specific CT-related skeletal muscle parameters predictive of postoperative survival in liver transplant (LT) patients with hepatocellular carcinoma (HCC) remain unclear. There is increasing evidence supporting the role of fatty acids and their lipid intermediates in regulating skeletal muscle mass and function, the relationship between lipoprotein subfractions and body composition remains unclear. Adult patients with HCC who underwent LT between January 2015 and September 2022 were retrospectively analyzed. CT parameters, including skeletal muscle index (SMI), psoas muscle index (PMI), skeletal muscle density (SMD), visceral and subcutaneous adipose tissue (VAT and SAT), and the VAT/SAT ratio at the L3 level, and lipid profiles, were assessed prior to LT. Of the 284 LT patients with HCC, 224 underwent CT (L3 level) within 3months of LT, and 82 (37%) were diagnosed with myosteatosis. Patients with myosteatosis exhibited significantly lower 1- and 3-year survival rates (p = 0.002, p = 0.01), a trend persisting even beyond the Milan criteria (p = 0.004, p = 0.04). After adjusting for covariates, SMD demonstrated a significant negative correlation with post-transplant survival (HR: 0.90, [95% Confidence Interval(CI): 0.83-0.98], C-statistic: 0.78, p = 0.009). Pearson's correlation analysis revealed a positive correlation between high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A1(ApoA1) levels and SMD. Multivariate stepwise regression analysis demonstrated that every 10 Hounsfield unit decrease in SMD was associated with a 0.16mmol/L decrease in HDL-C and a 0.18g/L decrease in ApoA1. Routine abdominal CT scans for assessing skeletal muscle density before LT were significantly associated with post-transplant mortality. Furthermore, abnormal HDL-C and ApoA1 levels before LT were associated with myosteatosis.

Liver disease and transplantation in telomere biology disorders: An international multicenter cohort.

Patients with telomere biology disorders (TBD) develop hepatic disease, including hepatitis, cirrhosis, and hepatopulmonary syndrome. No specific treatment exists for TBD-related liver disease, and the role of liver transplantation (LT) remains controversial. Our study objectives were to describe the clinical characteristics, management, and outcomes in patients with TBD-related liver disease, and their LT outcomes. Data from 83 patients with TBD-associated liver disease were obtained from 17 participating centers in the Clinical Care Consortium of Telomere-Associated Ailments and by self-report for our retrospective, multicenter, international cohort study. Group A ("Advanced") included 40 patients with advanced liver disease. Of these, 20 underwent LT (Group AT). Group M ("Mild") included 43 patients not warranting LT evaluation, none of whom were felt to be medically unfit for liver transplantation. Supplemental oxygen requirement, pulmonary arteriovenous malformation, hepatopulmonary syndrome, and higher bilirubin and international normalized ratio values were associated with Group A. Other demographics, clinical manifestations, and laboratory findings were similar between groups. Six group A patients were declined for LT; 3 died on the waitlist. Median follow-up post-LT was 2.9 years (range 0.6-13.2y). One-year survival post-LT was 73%. Median survival post-LT has not been reached. Group AT patients had improved survival by age compared to all nontransplant patients (log-rank test p = 0.02). Of 14 patients with pretransplant hypoxemia, 8 (57%) had improved oxygenation after transplant. LT recipients with TBD do not exhibit excessive posttransplant mortality, and LT improved respiratory status in 57%. A TBD diagnosis should not exclude LT consideration.

Liver Transplantation Profile Among Teenagers in the United States

PurposeIndications for liver transplantation (LT) vary across age groups. We identified predictors of outcomes for teenage LT waitlisted candidates and recipients in the United States from 2008 to 2022. MethodsThe Scientific Registry of Transplant Recipients 2008–2022 provided data (clinical, sociodemographic, indications for LT, outcomes) for all teenagers (13–19 years) waitlisted for LT in the United States. Sociodemographic and clinical characteristics, including primary listing diagnoses, were evaluated and compared by age group (13–16 vs. 17–19 years) among waitlisted teenage candidates. ResultsThere were 2,813 teenage LT candidates listed between 2008 and 2022. The most common LT indication was acute liver disease (23.5%), followed by biliary atresia or hypoplasia (11.9%), autoimmune hepatitis (11.1%), and primary sclerosing cholangitis (9.7%). In contrast, chronic viral hepatitis, metabolic dysfunction-associated steatotic liver disease, and alcohol-related liver disease (the most common indications in adults) did not exceed 1% each; 2.8% had hepatocellular carcinoma. Excluding the two most recent years, 67.2% of candidates received a transplant; mean time to transplant was 217.0 days (standard deviation 371.6). Independent predictors of receiving a transplant were a more recent calendar year, younger age, higher model for end-stage liver disease score, and an acute liver disease diagnosis (all p < .05). Among the LT group, 3-year survival was 90%, with an improving survival trend. Higher post-transplant mortality was associated with earlier years of transplantation, older age, having Medicaid, being retransplanted, and having hepatocellular carcinoma (adjusted hazard ratios >1, all p < .05). DiscussionIndications for LT among US teenagers are different from adults or younger children. There is a trend toward improved post-transplant outcomes.

The protective role of two oxindole derivatives is mediated by modulating NLRP3/caspase-1 and PI3K/AKT pathways in a preclinical animal model of hepatic ischemia reperfusion injury

AimHepatic ischemia reperfusion injury (HIRI) is a leading cause of mortality post liver transplantation, hypovolemic shock and trauma. In this study, we tested, on molecular bases, the possible protective role of two different derivatives of 2-oxindole in a preclinical model of HIRI in rats. Main methodsHIRI was operated in male Wistar albino rats and prophylactic treatment with oxindole-curcumin (Coxi) or oxindole-vanillin (Voxi) was carried out before the operation. The biochemical and histopathological investigations, in addition to the mechanistic characterizations of the effect of the tested drugs were performed. Key findingsHIRI was assured with elevated liver enzymes and marked changes in histopathological features, inflammatory response and oxidative stress. Pretreatment with Coxi and Voxi improved the hepatic histopathological alterations, reduced the elevated serum liver enzymes level and hepatic Malondialdehyde (MDA) content, increased the hepatic Superoxide Dismutase (SOD) activity and reduced Glutathione (GSH) content, downregulated the expression of TNF-α, IL-6, Nod-Like Receptor p3 (NLRP3), Cleaved caspase1, Cleaved caspase 3 proteins, alongside the expression level of IL-1β, ICAM-1, VCAM-1 and BAX genes, attenuated NF-кB p-P65 Ser536 and Myeloperoxidase (MPO)-positive neutrophils, and activated the PI3K/AKT pathway. SignificanceCoxi and Voxi have promising hepatoprotective activity against HIRI in rats through ameliorating the biochemical and histopathological alterations, attenuating inflammatory and oxidative stress status by modulating the inflammatory TNF-α/ICAM-1, the pyroptosis NLRP3/Caspase-1, and the antioxidant PI3K/AKT pathways.

Influence of donor age and donor-recipient age difference on intimal hyperplasia in pediatric patients with young and adult donors vs. adult patients after heart transplantation.

Optimal selection and allocation of donor hearts is a relevant aspect in transplantation medicine. Donor age and cardiac allograft vasculopathy (CAV) affect post-transplant mortality. To what extent donor age impacts intimal hyperplasia (CAVIH) in pediatric and adult patients after heart transplantation (HTx) is understudied. In a cohort of 98 HTx patients, 58 pediatric (24.1% with adult donors) and 40 adult patients, we assessed the effect of donor age and donor-recipient age difference (D-R) on the continuous parameter of maximal intima thickness (mIT) in optical coherence tomography. We evaluated their predictive value regarding higher mIT and the prevalence of CAVIH, defined as mIT > 0.3 mm, and compared it to established CAV risk factors. In the overall population, donor age correlated with mIT (p < 0.001), while in the pediatric subpopulation, both donor age and D-R correlated with mIT (p < 0.001 and p = 0.002, respectively). In the overall population, donor age was a main predictor of higher mIT and CAVIH (p = 0.001 and p = 0.01, respectively) in addition to post-transplant interval, arterial hypertension, and dyslipidemia. In the pediatric patients, dyslipidemia remained a main predictor of both higher mIT and CAVIH (p = 0.004 and p = 0.040, respectively), while donor age and D-R were not. While there was an effect of the non-modifiable parameter of donor age regarding maximal intimal thickness, a stronger association was seen between the modifiable risk factor dyslipidemia and higher maximal intimal thickness and CAVIH in both the overall population and the pediatric subpopulation.

Sex-based Disparities in Liver Transplantation for Hepatocellular Carcinoma and the Impact of the Growing Burden of NASH.

The cause of liver disease is changing, but its impact on liver transplantation (LT) for hepatocellular carcinoma (HCC) in women and men is unclear. We performed a nationwide study to assess the prevalence and posttransplant survival outcomes of the various causes of liver disease in women and men with HCC. Data were obtained from the United Network for Organ Sharing database from 2000 to 2022. Data related to the listing, transplant, waitlist mortality, and posttransplant mortality for HCC were extracted. The proportion of HCC related to the various causes of liver disease among LT candidates and recipients and posttransplant survival were compared between women and men. A total of 51 721 individuals (39 465 men, 12 256 women) with HCC were included. From 2000 to 2022, nonalcoholic steatohepatitis (NASH) was the fastest-growing cause of liver disease among female LT candidates with HCC (P < 0.01), followed by alcohol-associated liver disease. NASH overtook chronic hepatitis C as the leading cause of liver disease in 2020 and 2022 among waitlisted women and men with HCC, respectively. Female patients with HCC spent a significantly longer time on the LT waitlist compared with male patients (β: 8.73; 95% confidence interval [CI], 2.91-14.54). Female patients with HCC from alcohol-associated liver disease also have a lower probability of receiving LT (subdistribution hazard ratio: 0.90; 95% CI, 0.82-0.99). Among transplant recipients with NASH HCC, female sex was associated with lower posttransplant mortality compared with male sex (hazard ratio: 0.79; 95% CI, 0.70-0.89; P < 0.01). Women have a significantly longer waitlist duration compared with men. NASH is now the leading cause of liver disease among both female and male LT candidates and recipients with HCC.