Outcome Of Liver Transplantation Research Articles

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 150-155 mEq/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 125-130 mEq/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 150 mEq/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.

Outcomes of Bridging Therapy in Liver Transplantation for Hepatocellular Carcinoma

Background: Liver transplantation (LT) is a method for treating hepatocellular carcinoma (HCC) with satisfactory outcomes. One of the novel methods for predicting LT outcomes is the Metroticket 2.0 model. The disease in patients initially within the Milan criteria (MC) may progress while on a transplantation waitlist; thus, various transplantation bridging therapy (BT) methods are proposed for patients to stay within the MC and optimize the LT outcome. Methods: We performed a retrospective analysis of patients who underwent LT for HCC at an oncological and transplantation center in northern Poland. Patients who underwent (n = 10) or did not undergo (n = 11) BT were included. The primary endpoints of the study were mortality among the patients, HCC recurrence, and Metroticket 2.0 scores based on LT qualification results and explant pathology outcomes. The median follow-up length was 44.03 months. Results: Patients who underwent BT had significantly lower Metroticket 2.0 scores and greater AFP concentrations at baseline. At LT, there was no significant difference in Metroticket 2.0 scores or AFP concentrations between the groups. Explant Metroticket 2.0 scores were significantly lower in patients who received BT. A complete pathologic response was achieved in 30.0% of patients who underwent BT. The recurrence-free survival rates were 100% and 90.91% in patients who underwent and did not undergo BT, respectively. Overall survival was 80.0% and 81.81% in patients who underwent and did not undergo BT, respectively. Conclusions: BT should be considered only as a means of remaining within the LT criteria. Routine BT does not appear to be justified for LT patients.

Immune Checkpoint Inhibitors in the Pre-Transplant Hepatocellular Carcinoma Setting: A Glimpse Beyond the Liver

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the third leading cause of cancer-related death worldwide. Liver transplantation (LT) is the best therapy for most patients with non-metastatic HCC. In recent years, the management of patients with HCC has considerably changed, thanks to the improvement of molecular biology knowledge and the introduction of immunotherapy. To date, systemic therapy is authorized in the Western world only in patients with advanced HCC. However, this therapy could not only stabilize the tumour disease or improve survival but could display excellent response and lead to downstaging of the tumour that finally permits LT. There are increasing reports of patients that have performed LT after pretreatment with immune checkpoint inhibitors (ICIs). However, due to the intrinsic mechanism of ICIs, graft rejection might be favoured. In addition, chronic adverse effects affecting other organs may also appear after the end of therapy. This review aims to evaluate the readiness and outcomes of LT in patients with advanced HCC who have previously undergone treatment with ICIs. It seeks to identify the challenges, risks, and benefits associated with this conversion therapy. The integration of ICIs into the treatment paradigm for advanced HCC necessitates a nuanced approach to LT. While early evidence supports the feasibility of LT following ICIs therapy, there is an urgent need for standardized guidelines and more extensive longitudinal studies to optimize patient selection, timing, and post-transplant management.

Neighborhood-Level Deprivation Impacts Graft and Patient Outcomes Among Pediatric Liver Transplant Recipients.

The impact of social determinants of health (SDOH) on pediatric liver transplant outcomes has not been extensively investigated. The purpose of this study was to examine the effect of neighborhood-level deprivation on graft and patient survival among pediatric liver transplant recipients. This is a single-center observational study among children who received a primary liver transplant from March 1996 to March 2023. The Childhood Opportunity Index (COI) score was used to measure the degree of neighborhood deprivation. A total of 252 children were included, half (52.8%) were female and the majority were non-Hispanic White (71%). Half (53.6%) of the children had private insurance, and the median COI score was 64. A total of 28 children were transplanted from a very low-to-low COI area. Children in very low-to-low COI areas had worse patient (HR = 4.90, 95% CI = 1.41-17.04, p = 0.01) and graft (HR = 3.41, 95% CI = 1.19-9.75, p = 0.02) survival outcomes compared to children in moderate-to-very high areas when adjusting for clinical characteristics. COI score remained a significant predictor of graft survival after adjusting for race and insurance type (HR = 3.41, 95% CI = 1.12-10.40, p = 0.03). Pediatric liver transplant recipients from very low-to-low COI score areas have worse graft outcomes when accounting for clinical factors, race/ethnicity, and insurance status. Future research should investigate the impact of multiple, intersecting SDOH factors, rather than solely a collection of isolated variables.

Are the differences really different? understanding the role of induction immunosuppression on pediatric liver transplant outcomes.

Are the differences really different? understanding the role of induction immunosuppression on pediatric liver transplant outcomes.

Revisiting the Prognostic Influences of Donor-Recipient Size Mismatch in Deceased Donor Liver Transplantation.

Liver transplantation (LT) outcomes are influenced by donor-recipient size mismatch. This study re-evaluated the impact on graft size discrepancies on survival outcomes. Data from 53 389 adult LT recipients from the United Network for Organ Sharing database (2013-2022) were reviewed. The study population was divided by the body surface area index (BSAi), defined as the ratio of donor body surface area (BSA) to recipient BSA, into small-for-size (BSAi < 0.78), normal-for-size (BSAi 0.78-1.24), and large-for-size (BSAi > 1.24) grafts in deceased donor LT (SFSD, NFSD, and LFSD). Multivariate Cox regression and Kaplan-Meier survival analyses were conducted. The frequency of size mismatch in deceased donor LT increased over the past 10 y. SFSD had significantly worse 90-d graft survival (P < 0.01), and LFSD had inferior 1-y graft survival among 90-d survivors (P = 0.01). SFSD was hazardous within 90 d post-LT because of vascular complications. Beyond 1 y, graft size did not affect graft survival. LFSD risk within the first year was mitigated with lower model for end-stage liver disease (MELD) 3.0 scores (<35) or shorter cold ischemia time (<8 h). The negative impacts on donor-recipient size mismatch on survival outcomes are confined to the first year post-LT. SFSD is associated with a slight decrease in 90-d survival rates. LFSD should be utilized more frequently by minimizing cold ischemia time to <8 h, particularly in patients with MELD 3.0 scores below 35. These findings could improve donor-recipient matching and enhance LT outcomes.

Improved Outcomes of Liver Transplantation in Patients With Hepatitis C, Following the Introduction of Innovative Antiviral Therapies

BackgroundThe treatment landscape for Hepatitis C virus (HCV) underwent a significant shift with the introduction of direct-acting antiviral (DAA) medications in late 2013. This study aimed to evaluate the impact of DAAs on liver transplantation outcomes, examining both the benefits and any potential drawbacks associated with their use. Methods and materialsA retrospective registry analysis of the United Network for Organ Sharing database was done for liver transplants in patients diagnosed with Hepatitis C, that were performed in the United States from January 2000 to May 2020. ResultsThe study was divided into 2 subgroups, based on the timing of new DAA medication FDA approved. The only significant difference between the two cohorts is the recipient’s age. The data analysis showed a significant overall 5-year graft survival improvement in the 2014-2020 group compared to the 2000-2013 group, from a mean of 64.8% in 2000-2013 to a mean of 76% in 2014-2020 (P<0.001). Interestingly, when we compared the 5-year graft survivals with recipients who had a donor above age 50, the graft survival rate difference was even more significant (74% vs. 56%, P<0.001), as some studies have shown a suboptimal graft outcome, when the donor age is above 40 years old. Not only has the utilization of DCD livers increased significantly after 2014, but the graft survival in this cohort has also been significantly higher.(P<0.001). ConclusionThe emergence of DAAs in 2013 marked a watershed moment in the management of HCV, offering high cure rates, minimal side effects, and shorter treatment durations, to a point that the short- and long-term outcomes of liver transplant for HCV is almost equal to the other causes of liver transplantation.

The effects of underlying inflammatory bowel disease on the outcomes of primary sclerosing cholangitis liver transplant recipients

IntroductionInflammatory bowel disease (IBD) influences primary sclerosing cholangitis (PSC) severity, however, the impact of IBD on PSC liver transplantation (LT) outcomes is poorly understood. We aimed to elucidate the impact of IBD in modulating PSC LT outcomes. MethodsUsing UNOS data from 2010 through 2021, we identified PSC LT candidates with and without (±) IBD. We used adjusted competing-risk regression analysis to evaluate waitlist outcomes, Kaplan-Meier analysis to assess graft survival, and Cox proportional hazards modeling to identify factors associated with graft survival. ResultsOut of 5,586 PSC candidates added to the waitlist, 3,652 patients had IBD. Older age (SHR 1.01; 95 %CI 1.01–1.02) and initial MELD/PELD (SHR 1.03; 95 %CI 1.02–1.04) were associated with increased risk of waitlist mortality, while private insurance (SHR 0.00; 95 %CI 0.00–0.01) with reduced risk. PSC-IBD LT recipients had increased prevalence of cholangiocarcinoma (4.8 % vs 3.4 %, p=0.005). Longer donor cold ischemia times (HR 1.06; 95 %CI 1.03–1.09), presence of recipient diabetes (HR 1.52; 95 %CI 1.13–2.05), and employment (HR 0.75, 95 %CI 0.60–0.94) had an increased risk of graft failure among PSC patients with IBD, not seen in those without IBD. ConclusionRegardless of IBD, LT for PSC results in excellent outcomes. Certain clinicodemographic factors impacted waitlist and recipient mortality highlighting potential targets to enhance outcomes.

S1762 Trends and Outcomes of Liver Transplant in Patients with Alcohol-Associated Liver Cirrhosis Versus Non-Alcohol Associated Liver Cirrhosis: A Nationwide Study

S1762 Trends and Outcomes of Liver Transplant in Patients with Alcohol-Associated Liver Cirrhosis Versus Non-Alcohol Associated Liver Cirrhosis: A Nationwide Study

S2064 Perioperative Outcomes of Liver Transplantation in Patients With Prior Bariatric Surgery: A Nationwide Analysis

S2064 Perioperative Outcomes of Liver Transplantation in Patients With Prior Bariatric Surgery: A Nationwide Analysis

Acceptable outcomes of liver transplantation in uninsured patients under the coverage of a state assistance program.

The lack of health insurance is a major barrier in the access to healthcare even in case of life-saving procedures such as liver transplantation (LT). Concerns about worse outcomes in uninsured patients have also discouraged the evaluation and transplantation of patients without adequate health insurance coverage. The aim of this study is to evaluate outcomes from the largest cohort of uninsured patients who underwent LT with the support of a state payment assistance program (also called charity care). This study included all consecutive patients who underwent LT at a single center from 2002 to 2020. Demographic, clinical, social variables and outcome metrics were collected and compared between insured and uninsured patients. Among a total of 978 LT recipients, 594 had private insurance, 324 government insurance (Medicare/Medicaid), 60 were uninsured and covered under a state charity care program. In the charity care group, there was a higher proportion of Hispanic subjects, single marital status, younger age, and high-MELD score patients. The 1- and 3-year patient survival rates were 89.0% and 81.8% in private insurance patients, 88.8% and 80.1% in government insurance recipients, and 93.3% and 79.6% in those with charity care (p=0.49). There was no difference in graft survival between insured and uninsured patients (p=0.62). The three insurance groups presented similar hospital length-of-stay and 30-day readmission rates. In both univariate and multivariate analysis, uninsured status (charity care) was not associated with worse patient survival (HR:1.23, 95%CI: 0.84-1.80, p=0.29) or graft survival (HR:1.22, 95%CI:0.84-1.78, p=0.29). In conclusion, there was no difference in outcomes after LT between insured and uninsured patients. A charity care program may be an effective tool to mitigate socio-economic disparities in both outcomes and access to LT.

The Outcomes of Liver Transplantation in Highly Dependent Incapacitated Patients with Intellectual and Developmental Disabilities.

Background/Objectives: Data regarding the outcomes of liver transplantation in disabled, highly dependent, and legally incapacitated adults are scarce, likely due to the infrequency of these procedures in such populations. Multicenter studies in adult transplant centers have shown that patients with coexisting intellectual and developmental disabilities (IDDs) may be denied transplantation because of their expected low longevity and the complexities associated with managing post-transplant care. We examined the long-term patient and graft outcomes in highly dependent, incapacitated patients with IDDs who underwent elective transplantation for chronic liver disease. Methods: Six adult patients who underwent liver transplantation for primary biliary cholangitis (n = 2), hepatitis C cirrhosis (n = 2), Wilson's disease (n = 1), and autoimmune hepatitis (n = 1) were included. The main causes of their disability were infantile cerebral palsy, myotonia, and Niemann-Pick disease. Results: Four of the six patients were women, with a median age of 26 (range: 23-36) years. Only one patient died during follow-up. Their 1- and 5-year survival rates were 100 and 75%, respectively, which were not statistically different from those of the general cohort of electively transplanted patients (95.8 and 90.1%, respectively) (p = 0.35). Conclusions: Adult patients who are highly dependent, disabled, or legally incapable should not be denied liver transplantation because of poor long-term survival rates. Physiological disorders and psychiatric comorbidities should not prevent patients from receiving life-saving surgeries due to poor postoperative compliance or low quality of life.

Innovative Strategies for Liver Transplantation: The Role of Mesenchymal Stem Cells and Their Cell-Free Derivatives.

Despite being the standard treatment for end-stage liver disease, liver transplantation has limitations like donor scarcity, high surgical costs, and immune rejection risks. Mesenchymal stem cells (MSCs) and their derivatives offer potential for liver regeneration and transplantation. MSCs, known for their multipotency, low immunogenicity, and ease of obtainability, can differentiate into hepatocyte-like cells and secrete bioactive factors that promote liver repair and reduce immune rejection. However, the clinical application of MSCs is limited by risks such as aberrant differentiation and low engraftment rates. As a safer alternative, MSC-derived secretomes and extracellular vesicles (EVs) offer promising therapeutic benefits, including enhanced graft survival, immunomodulation, and reduced ischemia-reperfusion injury. Current research highlights the efficacy of MSC-derived therapies in improving liver transplant outcomes, but further studies are necessary to standardize clinical applications. This review highlights the potential of MSCs and EVs to address key challenges in liver transplantation, paving the way for innovative therapeutic strategies.

Core outcome sets and benchmarking complications: Defining best practices for standardized outcome reporting in liver transplantation

The comparison of outcomes in liver transplantation (LT) is hampered by using clinically non-relevant surrogate endpoints and considerable variability in reported relevant post-transplant outcomes. Such variability stems from non-standard outcome measures across studies, variable definitions of the same complication, and different timing of reporting. The Clavien-Dindo classification was established to improve the rigor of outcome reporting but is non-specific to an intervention and there are unsolved dilemmas specifically related to liver transplantation. Core Outcome Sets (COS) have been used in other specialties to standardize outcomes research, but have not been defined for LT. Thus, we use the five major benchmarking studies published to date to define a 10-measure COS for LT using previously validated metrics. We further provide standard definitions for each of the 10 measures that may be used in international research on the topic. These definitions also include standard time-points for recording to facilitate between-study comparisons and future meta-analysis. These 10 outcomes are paired with 3 validated, procedure-independent metrics, including the Clavien-Dindo Classification and the Comprehensive Complications Index (CCI®). The Clavien scale and CCI® are specifically reviewed to enhance their utility in LT, and their use along with the COS is explored. We encourage future studies to employ this COS along with the Clavien-Dindo grading system &amp; CCI® to improve reproducibility and generalizability of research concerning liver transplantation.

Genitourinary tumors and liver transplantation: A comprehensive review.

Liver transplantation is as a crucial therapeutic option for patients with end-stage liver disease, but the persistent organ shortage emphasizes a need to explore unconventional donor sources, including individuals with a history of malignancies. This review investigates the viability of liver donation from individuals with current or past genitourinary malignancies, focusing on renal, prostate and urinary bladder cancers. The rising incidence of urogenital malignancies among potential donors is thought to result from increasing donor age. Analysis of transmission risks reveals low rates of donor-derived cancer transmission, particularly for early-stage renal and prostate cancers. Recipients with a history of genitourinary malignancy pose complex challenges regarding post-transplant immunosuppression and cancer recurrence. Nonetheless, the evidence suggests acceptable outcomes can be achieved with careful patient selection and tailored management strategies. Recommendations for pre-transplant evaluation and post-transplant surveillance are discussed, highlighting the need for individualized approaches in this patient population. Further prospective studies are warranted to refine guidelines and optimize outcomes in liver transplantation for patients with genitourinary malignancies.

Interleukin 6 and interleukin 17A serum levels and gene- polymorphisms in the development of early allograft rejection in living donor liver transplant recipients

The aim of this study is to evaluate the role of serum level of Interleukin 6(IL-6) and Interleukin 17 (IL-17) in liver transplantation outcome for living recipients, Analyze the relation between the gene polymorphism and the occurrence of rejection after liver transplantation and Study the relation between the gene polymorphism and the occurrence of different infectious complications. The study was conducted in March 2023 and included 60 healthy volunteers from the National Liver Institute (NLI) blood bank at Menoufia University and 120 live donation liver recipient patients at NLI. During one month of liver transplantation, the cytokine levels (IL-17, IL-6 proteins, IL-6 G-174C, and IL-17 A rs2275913 gene polymorphism) and CD4 levels for 60 patients of 120 live donation liver recipient patients whom early reject transplanted tissue and the same parameters were measured after 6 months follow up for non-reject group. The main finding of this study was that the post-transplant rejection group and the post-transplant non-rejection and control groups differed significantly in the genotype frequency (CC, CG, and GG) or alleles of IL-6 G-174C (p = 0.011). On the other hand IL-17A rs2275913 gene polymorphism and its alleles (p = 0.71) showed no statistically significant difference. We also observed that serum IL-17 levels, with 100% specificity and 100% sensitivity threshold, will be more sensitive and specific than serum IL-6 and CD4 count in differentiating post-transplant rejection from non-rejection patients. The results showed that there was no significant relationship between the genotypes and serum levels of interleukins and the type and degree of rejection. Proinflammatory cytokines might be useful indicators for distinguishing and early identifying unfavorable outcomes after transplantation, allowing for prompt and effective treatment intervention. To evaluate these findings, prospective clinical trials are required.

New prognostic model for liver transplantation outcomes in hepatocellular carcinoma

Background. Liver transplantation remains a priority treatment option for hepatocellular carcinoma in the presence of liver cirrhosis; yet precise outcome prediction post-operation continues to be a complex challenge. Existing prognostic model often overlook patient age and donor type. Enhanced models that incorporate these parameters can improve prediction accuracy and treatment efficacy, which is critically important in the dynamically evolving field of transplantation.Objective. The aim of this study is to develop a prognostic model for liver transplantation outcomes in patients with hepatocellular carcinoma and liver cirrhosis.Material and methods. This retrospective study included 69 patients with hepatocellular carcinoma on the background of liver cirrhosis who underwent liver transplantation between May 2010 and December 2022. Of these, 42 patients (61%) received organs from living donors, and 27 (39%) from deceased donors. The study involved analysis of alpha-fetoprotein levels in blood, as well as assessment of radiological (maximum tumor nodule size, number of nodules) and histological parameters (maximum tumor nodule size, number of nodules, presence of vascular invasion). Cox regression model was used to predict recurrence-free survival, and the results for five-year recurrence-free survival, recipient age, and donor type were reused in the Cox model to predict overall survival.Results. Four models for predicting recurrence-free survival and overall survival based on histological and radiological data were developed, demonstrating high prognostic value with C-indexes on training/test data of 0.76/1; 0.73/1; 0.78/0.8; 0.6/0.8 respectively. All models showed recurrence-free survival prediction accuracy comparable to the Milan criteria. The model outcomes are available as a calculator on the website https://nadit.ru/calculate_HCC.Conclusion. The developed prognostic models are vital tools for personalized outcome prediction after liver transplantation for hepatocellular carcinoma. To enhance the accuracy of these models, further amalgamation and validation of data from various medical centers, as well as open scientific collaboration, are necessary.

Human leukocyte antigen compatibility and incidence of donor-specific antibodies in pediatric liver transplant recipients.

Antibody-mediated rejection following liver transplantation (LT) has been increasingly recognized, particularly with respect to the emergence of de novo donor-specific antibodies (DSAs) and their impact on graft longevity. While substantial evidence for adult populations exists, research focusing on pediatric LT outcomes remains limited. To investigate the prevalence of human leukocyte antigen (HLA) mismatches and DSA and evaluate their association with rejection episodes after pediatric LT. A cohort of pediatric LT recipients underwent HLA testing at Santa Casa de Porto Alegre, Brazil, between December 2013 and December 2023. Only patients who survived for > 30 days after LT with at least one DSA analysis were included. DSA classes I and II and cross-matches were analyzed. The presence of de novo DSA (dnDSA) was evaluated at least 3 months after LT using the Luminex® single antigen bead method, with a positive reaction threshold set at 1000 MFI. Rejection episodes were confirmed by liver biopsy. Overall, 67 transplanted children were analyzed; 61 received grafts from living donors, 85% of whom were related to recipients. Pre-transplant DSA (class I or II) was detected in 28.3% of patients, and dnDSA was detected in 48.4%. The median time to DSA detection after LT was 19.7 [interquartile range (IQR): 4.3-35.6] months. Biopsy-proven rejection occurred in 13 patients at follow-up, with C4d positivity observed in 5/13 Liver biopsies. The median time to rejection was 7.8 (IQR: 5.7-12.8) months. The presence of dnDSA was significantly associated with rejection (36% vs 3%, P < 0.001). The rejection-free survival rates at 12 and 24 months were 76% vs 100% and 58% vs 95% for patients with dnDSA anti-DQ vs those without, respectively. Our findings highlight the importance of incorporating DSA assessment into pre- and post-transplantation protocols for pediatric LT recipients. Future implications may include immunosuppression minimization strategies based on this analysis in pediatric LT recipients.

249.2: Outcomes of liver transplantation in patients 60 years and older: a multivariate analysis using penalized Cox regression.

249.2: Outcomes of liver transplantation in patients 60 years and older: a multivariate analysis using penalized Cox regression.

P.367: Outcomes of liver transplantation: A single-center experience. (First Central Hospital of Mongolia).

P.367: Outcomes of liver transplantation: A single-center experience. (First Central Hospital of Mongolia).