Liver Transplant Candidates Research Articles

Obesity management for the pre–liver transplant and post–liver transplant patient

Obesity management for the pre–liver transplant and post–liver transplant patient

MELD-Na Alterations on the Liver Transplant Waiting List and Their Impact on Listing Outcome.

Dynamic MELD deterioration (Delta MELD) during waiting time was shown to have significant impact on post-transplant survival. The aim of this study was to analyze the impact of MELD-Na score alterations on waiting list outcomes in liver transplant candidates. 36,806 patients listed at UNOS for liver transplantation in 2011-2015 were analyzed according to their delisting reasons. Several different MELD-Na alterations during waiting time were analyzed (e.g., maximal change, last change before delisting/transplantation). Outcome estimates were calculated according to MELD-Na scores at listing and Delta MELD. Patients who died while on the waiting list showed a significantly higher deterioration in MELD-Na during the waiting time (6.8 ± 8.4 points) than stable patients who remained actively listed (-0.1 ± 5.2 points; p < 0.01). Patients who were considered too healthy for transplantation improved by more than 3 points on average during the waiting time. The mean peak MELD-Na alteration during the waiting time was 10.0 ± 7.6 for patients who died on the waiting list, compared to 6.6 ± 6.1 in the group of patients who finally underwent transplantation. Deterioration of MELD-Na during waiting time and maximal MELD-Na deterioration have a significant negative impact on the liver transplant waiting list outcome.

NASH is the Leading Cause of Hepatocellular Carcinoma in Liver Transplant Candidates

NASH is the Leading Cause of Hepatocellular Carcinoma in Liver Transplant Candidates

Advancing the Field of Pediatric Liver Transplantation: Urgent Action Items Identified During the 2022 Society of Pediatric Liver Transplantation Meeting.

Advancing the Field of Pediatric Liver Transplantation: Urgent Action Items Identified During the 2022 Society of Pediatric Liver Transplantation Meeting.

Regional transplant rates depend more on physician-dependent variables than on proximity to transplant center

PurposeThe objective of this work was to uncover inequalities in access to liver transplantation in Bavaria, Germany.MethodsFor this purpose, the annual transplantation rate per 1 million inhabitants for the respective districts was determined from the aggregated postal codes of the place of residence of transplanted patients. The variables examined were proximity and travel time to the nearest transplant center, as well as the care category of the regional hospital. In addition, we assessed whether the head of gastroenterology at the regional hospital through which liver transplant candidates are referred was trained at a liver transplant center.ResultsWe could not demonstrate a direct relationship between proximity or travel time to the nearest transplant center and access to liver transplantation. Multivariate regression analysis shows that liver transplant training (p < 0.0001) of the chief physician (gastroenterologist) of the regional hospital was the most decisive independent factor for access to liver transplantation within a district.ConclusionWe show that the transplant training experience of the head of gastroenterology at a regional hospital is an independent factor for the regional transplantation rate. Therefore, it appears important to maintain some liver transplant expertise outside the transplant centers in order to properly identify and assign potential transplant candidates for transplantation.

Liver Transplant in Patients with Hepatocarcinoma: Imaging Guidelines and Future Perspectives Using Artificial Intelligence.

Hepatocellular carcinoma is the most common primary malignant hepatic tumor and occurs most often in the setting of chronic liver disease. Liver transplantation is a curative treatment option and is an ideal solution because it solves the chronic underlying liver disorder while removing the malignant lesion. However, due to organ shortages, this treatment can only be applied to carefully selected patients according to clinical guidelines. Artificial intelligence is an emerging technology with multiple applications in medicine with a predilection for domains that work with medical imaging, like radiology. With the help of these technologies, laborious tasks can be automated, and new lesion imaging criteria can be developed based on pixel-level analysis. Our objectives are to review the developing AI applications that could be implemented to better stratify liver transplant candidates. The papers analysed applied AI for liver segmentation, evaluation of steatosis, sarcopenia assessment, lesion detection, segmentation, and characterization. A liver transplant is an optimal treatment for patients with hepatocellular carcinoma in the setting of chronic liver disease. Furthermore, AI could provide solutions for improving the management of liver transplant candidates to improve survival.

Cardiovascular assessment of candidates for liver transplant

Cardiovascular events are the most important cause of morbidity and mortality after liver transplant (LT), since many recipients are older with cardiovascular risk factors and pathophysiology particular to end stage liver disease. Moreover, the LT procedure is associated with a unique cardiac risk. Detection of cardiovascular disease and stratification of risk have, therefore, an important impact on the prognosis of these patients.

Ethnic disparities in waitlist outcomes of patients with nonalcoholic steatohepatitis listed for liver transplantation in the US.

NASH is the fastest-growing cause of liver cirrhosis and is the leading indication for liver transplantation (LT). However, significant racial and ethnic disparities in waitlist outcomes and LT allocation may unfairly disadvantage minorities. Our aim was to characterize racial and ethnic disparities in waitlist mortality and transplantation probability among patients with NASH. This is a retrospective analysis of the United Network for Organ Sharing registry data of LT candidates from January 1, 2000 to December 31, 2021. Outcomes analysis was performed using competing risk analysis with the Fine and Gray model. The multivariable adjustment was conducted, and mixed-effect regression was used to compare the model for end-stage liver disease scores at listing and removal. Of 18,562 patients with NASH cirrhosis, there were 14,834 non-Hispanic Whites, 349 African Americans, 2798 Hispanics, 312 Asians, and 269 of other races/ethnicities; African American (effect size: 2.307, 95% CI: 1.561-3.053, and p < 0.001) and Hispanic (effect size: 0.332, 95% CI: 0.028-0.637, p = 0.032) patients were found to have a significantly higher model for end-stage liver disease scores at the time of listing than non-Hispanic Whites. African Americans had a higher probability of receiving LT relative to non-Hispanic Whites (subdistribution HR: 1.211, 95% CI: 1.051-1.396, and p = 0.008). However, Hispanic race/ethnicity was associated with a lower transplantation probability (subdistribution HR: 0.793, 95% CI: 0.747-0.842, and p < 0.001) and increased waitlist mortality (subdistribution HR: 1.173, CI: 1.052-1.308, and p = 0.004) compared with non-Hispanic Whites. There are significant racial and ethnic disparities in waitlist outcomes of patients with NASH in the US. Hispanic patients are less likely to receive LT and more likely to die while on the waitlist compared with non-Hispanic Whites despite being listed with a lower model for end-stage liver disease scores.

Quantitative Prediction of Posttransplant Hepatocellular Carcinoma Prognosis Using ADV Score: Validation with Korea-Nationwide Transplantation Registry Database

ObjectiveThe aim of this study is to validate the prognostic impact of ADV score (α-fetoprotein [AFP]–des-γ-carboxyprothrombin [DCP]–tumor volume [TV] score) for predicting prognosis of hepatocellular carcinoma (HCC) following liver transplantation (LT). BackgroundADV score has been reported as a prognostic surrogate biomarker of HCC following LT and hepatectomy. MethodsThe study patients were 1599 LT recipients selected from the Korean Organ Transplantation Registry database. ResultsDeceased-donor and living-donor LTs were performed in 143 and 1456 cases, respectively. Weak correlation was present among AFP, DCP, and TV. The viable HCC group showed ADV score-dependent disease-free survival (DFS) and overall patient survival (OS) rates from 1log to 10log (p<0.001). Prognosis of complete pathological response group was comparable to that of ADV score <1log (p≥0.099). ADV score cutoff of 5log (ADV-5log) for DFS and OS was obtained through receiver operating characteristic curve analysis with area under the curve ≥0.705. Both ADV-5log and Milan criteria were independent risk factors for DFS and OS, and their prognostic impacts were comparable to each other. Combination of these two factors resulted in further prognostic stratification, showing hazard ratios for DFS and OS as 2.98 and 2.26 respectively for one risk factor and 7.92 and 8.19 respectively for two risk factors (p<0.001). ABO-incompatible recipients with ADV score ≥8log or two risk factors showed higher recurrence rates. ConclusionsThis validation study revealed that ADV score is a reliable surrogate biomarker for posttransplant HCC prognosis, which can be used for selecting LT candidates and guiding risk-based posttransplant follow-up surveillance.

Demographic inequities exist and influence transplant outcomes in liver transplantation for acute alcohol-associated hepatitis

BackgroundLiver transplantation has inherent disparities but data is scarce in liver transplant (LT) candidates with acute alcohol-associated hepatitis (AAH). We aimed to investigate demographic inequities and its impact on survival outcomes among AAH LT candidates. MethodsA retrospective analysis using the United Network of Organ Sharing database was conducted between 2000 and 2021. 25 981 LT recipients with alcohol-associated liver cirrhosis and 662 recipients with AAH were included. Waitlisted candidates were also evaluated. ResultsIn comparison with alcohol-associated liver cirrhosis, AAH LT recipients were more likely Asian or “other” race and younger. Hispanics demonstrated better graft and patient survival (p < 0.05) but were less likely to be waitlisted and transplanted for AAH than for liver cirrhosis. Women with AAH were more likely to be waitlisted and transplanted. Pre-existing diabetes and male sex were associated with higher graft failure (25% and 8% respectively). Increasing recipient age were 2% more likely to experience negative outcomes. Chronicity of liver disease did not impact graft (p = 0.137) or patient survival (p = 0.145). ConclusionOur results revealed demographic factors have a significant impact on transplant listing, organ allocation and survival outcomes. Further investigations are imperative to minimize disparities in LT evaluation and provide equity in healthcare.

Patient-reported outcomes and patient-reported outcome measures in liver transplantation: a scoping review.

Generic or condition-specific Patient-reported Outcome Measures (PROMs) are used to measure physical, mental, and social aspects of health to promote patient-centered care. This scoping review aims to identify and summarize generic and condition-specific PRO domains and PROMs that have been assessed and used in liver transplant (LT) candidates and recipients. We searched Medline, Embase, Cochrane Database of Systematic Reviews and Register of Trials, PsychInfo, and CINAHL from inception to 08/26/2020. Included studies addressed a PRO or PROM in LT candidates or recipients. After screening, 341 studies yielded 189 unique PRO domains. Mental health domains (depression, anxiety, and guilt) were most frequently assessed, followed by domains of physical and social health. Fifty-one generic and three condition-specific unique PROMs were identified, with only 13% (n = 45) of studies including condition-specific tools. The most frequent PROMs were the SF-36, Nottingham Health Profile, Hospital Anxiety and Depression Scale, followed by the Liver Disease Quality of Life (LDQoL). Very few studies used transplant-specific PROMs, which may partly be related to the scarcity of LT-specific instruments. We will use these results in future qualitative research to identify PROs and PROMs to build an electronic PROM toolkit to facilitate patient-centered LT care.

Utility of an Artificial Intelligence Enabled Electrocardiogram for Risk Assessment in Liver Transplant Candidates.

Post-operative cardiac complications occur infrequently but contribute to mortality after liver transplantation (LT). Artificial intelligence-based algorithms based on electrocardiogram (AI-ECG) are attractive for use during pre-operative evaluation to screen for risk of post-operative cardiac complications, but their use for this purpose is unknown. The aim of this study was to evaluate the performance of an AI-ECG algorithm in predicting cardiac factors such as asymptomatic left ventricular systolic dysfunction or potential for developing post-operative atrial fibrillation (AF) in cohorts of patients with end-stage liver disease either undergoing evaluation for transplant or receiving a liver transplant. A retrospective study was performed in two consecutive adult cohorts of patients who were either evaluated for LT or underwent LT at a single center between 2017 and 2019. ECG were analyzed using an AI-ECG trained to recognize patterns from a standard 12-lead ECG which could identify the presence of left ventricular systolic dysfunction (LVEF < 50%) or subsequent atrial fibrillation. The performance of AI-ECG in patients undergoing LT evaluation is similar to that in a general population but was lower in the presence of prolonged QTc. AI-ECG analysis on ECG in sinus rhythm had an AUROC of 0.69 for prediction of de novo post-transplant AF. Although post-transplant cardiac dysfunction occurred in only 2.3% of patients in the study cohorts, AI-ECG had an AUROC of 0.69 for prediction of subsequent low left ventricular ejection fraction. A positive screen for low EF or AF on AI-ECG can alert to risk of post-operative cardiac dysfunction or predict new onset atrial fibrillation after LT. The use of an AI-ECG can be a useful adjunct in persons undergoing transplant evaluation that can be readily implemented in clinical practice.

Vaccination for Cirrhosis and Liver Transplant Patients

Patients with cirrhosis and liver transplantation (LT) have a higher risk of infections, complications and death. Vaccines have historically been used to prevent and reduce the risk of complications from viral and bacterial infections. The population with cirrhosis and candidates for LT should be evaluated for immunity against the most relevant immuno-preventable infections, update corresponding immunizations according to the national vaccination program, and inoculate the missing vaccines based on these recommendations. In case of not reaching its inoculation prior to LT, in the post-LT period its vaccination status should be updated. All doctors involved in the health care of these patients must have knowledge about this important topic and be aware of the access and free availability for this population through the presentation of a special form incorporated into the National Immunization Program.

NAFLD: A pretransplant and post-transplant conundrum.

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A model for calculating the long-term estimated post-transplant survival of deceased donor liver transplant patients.

The estimated long-term survival (EPTS) score is used for kidney allocation. A comparable prognostic tool to accurately quantify EPTS benefit in deceased donor liver transplant (DDLT) candidates is nonexistent. Using the Scientific Registry of Transplant Recipients (SRTR) database, we developed, calibrated, and validated a nonlinear regression equation to calculate liver-EPTS (L-EPTS) for 5- and 10-year outcomes in adult DDLT recipients. The population was randomly split (70:30) into two discovery (N=26,372 and N=46,329) and validation cohorts (N=11,288 and N=19,859) for 5- and 10-year post-transplant outcomes, respectively. Discovery cohorts were used for variable selection, Cox proportional hazard regression modeling, and nonlinear curve fitting. Eight clinical variables were selected to construct the L-EPTS formula, and a five-tiered ranking system was created. Tier thresholds were defined and the L-EPTS model was calibrated (R2=0.96 [5-year] and 0.99 [10-year]). Patients' median survival probabilities in the discovery cohorts for 5- and 10-year outcomes ranged from 27.94% to 89.22% and 16.27% to 87.97%, respectively. The L-EPTS model was validated via calculation of receiver operating characteristic (ROC) curves using validation cohorts. Area under the ROC curve was 82.4% (5-year) and 86.5% (10-year). L-EPTS has high applicability and clinical utility because it uses easily obtained pre-transplant patients characteristics to accurately discriminate between those who are likely to receive a prolonged survival benefit and those who are not. It is important to evaluate medical urgency alongside survival benefit and placement efficiency when considering the allocation of a scarce resource. There are no funding sources related to this project.

Functional evaluation of right coronary artery with anomalous origin in cirrhotic liver transplant candidate.

Functional evaluation of right coronary artery with anomalous origin in cirrhotic liver transplant candidate.

An ethical analysis of obesity as a contraindication to pediatric liver transplant candidacy

Childhood obesity is becoming more prevalent in the United States (US) and worldwide, including among children in need of a liver transplant. Unlike with heart and kidney failure, end-stage liver disease (ESLD) is unique in that no widely available medical technology can re-create the life-sustaining function of a failing liver. Therefore, delaying a life-saving liver transplant for weight loss, for example, is much harder, if not impossible for many pediatric patients, especially those with acute liver failure. For adults in the United States, guidelines consider obesity a contraindication to liver transplant. Although formal guidelines are lacking in children, many pediatric transplant centers also consider obesity a contraindication to a pediatric liver transplant. Variations in practice among pediatric institutions may result in biased and ad hoc decisions that worsen healthcare inequities. In this article, we define and report the prevalence of childhood obesity among children with ESLD, review existing guidelines for liver transplant in adults with obesity, examine pediatric liver transplant outcomes, and discuss the ethical considerations of using obesity as a contraindication to pediatric liver transplant informed by the principles of utility, justice, and respect for persons.

Current research in liver transplantation during the Covid-19 pandemic

The coronavirus disease (Covid-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has drastically changed our daily life and clinical practice.Due to the reduction of liver transplantation and the liver injury caused by SARS-CoV-2 infection during the pandemic,the prognosis of waitinglisted liver transplant candidates is worse.Due to the long-term immunosuppressive therapy of liver recipients,their risk of infection is higher than the general population.Although some studies suggested that immunosuppressive therapy seems to have a protective effect in infected patients,it also leads to chronic infection.Due to the concerns about the risk of virus transmission,expert consensus does not recommend the utilization of donor livers with the history of Covid-19.Currently,published articles do not support the argument that virus can be transmitted to recipients through donor livers.Therefore,the feasibility of liver transplantation utilizing donor livers with SARS-CoV-2 infection remains controversial.In this article,current advances in liver transplantation during the Covid-19 pandemic are reviewed to provide a new perspective for liver transplantation in the future.

The Japanese 5-5-500 Rule Predicts Prognosis of Hepatocellular Carcinoma After Hepatic Resection.

The 5-5-500 rule has been proposed to increase the candidates of liver transplantation for patients with hepatocellular carcinoma with reasonable recurrence rates. However, the clinical significance of the 5-5-500 rule in patients who underwent hepatic resection for hepatocellular carcinoma has not been fully investigated. The study comprised 206 patients who had undergone primary hepatic resection for hepatocellular carcinoma between 2008 and 2018. We retrospectively investigated prognostic significance of the 5-5-500 rule and disease-free, as well as overall, survival and further prognostic stratification using inflammatory-based biomarkers. 132 patients (64%) were classified within the 5-5-500 rule, while 74 patients (36%) were classified outside the 5-5-500 rule. Among the patients outside the 5-5-500 rule, 62 patients had tumors greater than 5 cm, and 23 patients showed serum AFP levels greater than 500 ng/ml. In the multivariate analysis, being female (p<0.01), HBs-Ag positive (p<0.01), having an ICGR15 ≥15% (p=0.03), and being outside the 5-5-500 rule (p=0.01) were independent and significant predictors of disease-free survival, while being HBs-Ag positive (p=0.04), having poor tumor differentiation (p=0.03), and residing outside the 5-5-500 rule (p=0.01) were independent and negative predictors of overall survival. Elevated CRP-to-albumin ratio was associated with poor overall survival in the patients outside the 5-5-500 rule, but not in patients within the 5-5-500 rule (p=0.17). The 5-5-500 rule can be a prognostic factor in patients with hepatocellular carcinoma after hepatic resection. CRP-to-albumin ratio might be useful to stratify the outcomes in patients outside the 5-5-500 rule.

A Low Daily Intake of Simple Sugars in the Diet Is Associated with Improved Liver Function in Cirrhotic Liver Transplant Candidates.

(1) Background: We investigated, for the first time, whether dietary simple sugar intake affects MELD score changes over time in a cohort of cirrhotic liver transplant candidates. (2) Methods: the MELD score, dietary habits using a 3-day food diary, and visceral adipose tissue index (VATI) measured with CT scan were assessed in 80 consecutive outpatient cirrhotic patients at baseline, after counseling to follow current nutritional guidelines. The MELD score was reassessed after six months and the DELTA-MELD was calculated as the MELD at the second assessment minus the MELD at baseline. (3) Results: Compared with the baseline, the MELD score of cirrhotic patients at the end of the study was decreased, stable, or increased in 36%, 8% and 56% of patients, respectively. In separate multiple linear regression models, DELTA-MELD was positively and independently correlated with the daily intake of simple sugars expressed in g/kg body weight (p = 0.01) or as a percentage of total caloric intake (p = 0.0004) and with the number of daily portions of fruit, added sugar, jam, and honey (p = 0.003). These associations were present almost exclusively in patients with VATI above the median value. (4) Conclusions: In cirrhotic patients with high amounts of visceral adipose tissue the consumption of simple sugars and fructose should be limited to improve their clinical outcome.