Robotic recipient liver transplantation worldwide: a systematic review and meta-analysis of the first 93 patients, from feasibility to early outcomes.

Evidence-Based Incorporation of Serum Sodium Concentration Into MELD

Model for end-stage liver disease (MELD) for liver allocation: A 5-year score card

Liver Transplantation for Hepatocellular Carcinoma: Impact of the MELD Allocation System and Predictors of Survival

Liver transplantation for alcoholic hepatitis in the United States: Excellent outcomes with profound temporal and geographic variation in frequency.

The Survival Impact of Liver Transplantation in the MELD Era, and the Future for Organ Allocation and Distribution

First-Degree Living-Related Donor Liver Transplantation in Autoimmune Liver Diseases.

In a MELD-based economy, how can we fight off inflation?

Liver transplantation (LT) has been recognized as the most effective therapy for end-stage liver disease (ESLD). However, the question of whether LT can improve erectile function in patients with ESLD remains controversial. Therefore, we conducted this meta-analysis to evaluate the association between LT and erectile dysfunction (ED). According to the PRISMA guidelines, studies were included after conducting searches in four databases from March 2024 onwards. These databases included PubMed, Cochrane Library, Web of Science, and Embase. The primary outcome of interest was to compare the International Index of Erectile Function (IIEF) scores between patients after and before LT. Standardized mean differences (SMDs) and their corresponding 95% confidence intervals (CIs) were utilized to assess the relationship between LT and ED. The results showed that the LT group had higher IIEF-5 domain scores for erectile function compared to the control group (SMD =-0.31, 95% CI: -0.53 to -0.09), P=0.007). No heterogeneity or publication bias was detected in the results. Additionally, the IIEF-15 domain score was also found to be improved after LT. Specifically, the LT group had higher domain scores for erectile function (SMD =-0.77, 95% CI: -1.07 to -0.48, P<0.001), orgasmic function (SMD =-0.82, 95% CI: -1.12 to -0.52, P<0.001), sexual desire (SMD =-0.89, 95% CI: -1.19 to -0.59, P<0.001), intercourse satisfaction (SMD =-0.92, 95% CI: -1.22 to -0.62, P<0.001), and overall satisfaction (SMD =-0.87, 95% CI: -1.17 to -0.57, P<0.001). It is suggested by our meta-analysis that LT may contribute to improvements in erectile function among men with ESLD. This improvement may be related to the remarkable improvement in endocrine hormone disorders observed after LT. However, future studies with better designs and larger sample sizes are still needed to confirm our conclusions. Additionally, attention to erectile function before and after surgery in patients with liver failure is crucial.

TO THE EDITOR: We thank Bari and Sharma1 for their interest and editorial regarding our study demonstrating that low, rather than high, body mass index (BMI) confers increased risk for post–liver transplantation (LT) death and graft loss, specifically among patients with low Model for End‐Stage Liver Disease (MELD) scores.1 In response to their comments, we would like to make the following remarks to clarify their interpretation of our data and to provide additional data. First, we need to make 2 clarifications with respect to comments made in the editorial. Bari and Sharma1 astutely point out that implementation of the Share 15 policy could have influenced the associations we found between low BMI–low MELD patients with respect to their risk for death and graft loss. Although this would otherwise be an important factor to consider in an analysis such as ours, the patient population we studied spanned LT recipients in calendar years 2002 to 2011. Implementation of National Share 15 did not occur until June 2013; as such, in the context of our analyses and patient cohort, the implementation of National Share 15 is not applicable. However, it is true that Regional Share 15 was implemented in January 2005. Stratification of our analyses by the year 2005 generates a very uneven distribution of the data and results in unstable estimates for the time period spanning the 3‐year interval from 2002 to the end of 2004. Despite this, we did find that the significance of the interaction between low MELD and low BMI remains significant for the time period spanning 2005‐2011, which was during the Regional Share 15 era. The editorial also comments that our finding of increased risk for mortality and graft loss after LT among low MELD–low BMI patients might be explained by differences in the donor risk index (DRI) among recipients. However, as we stated in our manuscript, our multivariate analyses included DRI in the models, and the interaction between low MELD and low BMI with respect to mortality and graft loss remained significant, indicating that our findings were not accounted for by biases toward giving higher DRI organs to the low MELD–low BMI patients. The editorial further suggests that consideration of serum sodium and LT year should be included in the multivariate analyses and also that it is of interest to investigate the associations between low MELD and low BMI, using an even lower cutoff for MELD (25th percentile, which would be MELD ≤ 12). We agree with Bari and Sharma1 that these analyses are of interest, and we provide the results of the suggested analyses here. With the addition of serum sodium and LT year to the multivariate analyses (which also included age, sex, ethnicity, liver disease diagnosis, hepatocellular carcinoma diagnosis, diabetes, ascites, and DRI), the interaction between low MELD and low BMI remained statistically significant, and the statistical significance was maintained regardless of the MELD cutoff we used (MELD ≤ 12, MELD ≤ 19, or MELD ≤ 26). Data are shown for risk of death and risk of graft loss at 3 months after LT, stratified by MELD cutoff in Table 1. These data demonstrate that as the MELD score decreases, the hazard ratios for risk of death or graft loss among low MELD–low BMI patients increase in a stepwise fashion. Table 1 - Hazard Ratio for Death or Graft Loss at 3 Months After LT Among Low BMI (<18.5 kg/m2) Patients Stratified by MELD Score Outcome (3 Months After LT) Hazard Ratio (95% Confidence Interval)a P Values MELD ≤ 12 Patient death 3.22 (1.84‐5.64) <0.001 Graft loss 2.36 (1.43‐3.88) 0.002 MELD ≤ 19 Patient death 2.06 (1.32‐3.21) 0.005 Graft loss 1.66 (1.16‐2.38) 0.005 MELD ≤ 26 Patient death 1.67 (1.14‐2.45) 0.02 Graft loss 1.37 (1.00‐1.89) 0.03 aAll models are adjusted for age, sex, ethnicity, serum sodium, LT year, liver disease diagnosis, hepatocellular carcinoma diagnosis, diabetes, ascites, and DRI. We conclude our letter by addressing the concepts of functional status and sarcopenia as they apply to our study and interpretation of our results. Although we included the Karnofsky Performance Score (KPS) in a subset of our multivariate analyses as the only available marker in the United Network for Organ Sharing (UNOS) data set of a patient's functional status, the KPS is well‐known to be inconsistently applied across transplant programs and, as such, is unfortunately not an ideal variable for assessing functional status in UNOS analyses for this reason. Regardless, as we discuss in our article, our demonstration of increased risk for patient death and graft loss after LT among low MELD–low BMI patients is highly suggestive that malnourishment, sarcopenia, and decreased functional status could be underlying factors related to the risk for poor outcomes in these patients. Our findings are strongly supported by data from Tandon et al.3 demonstrating that, among patients listed for LT, sarcopenic patients with low MELD (<15) had an increased mortality risk compared to low MELD patients without sarcopenia, which dovetails nicely with our findings of increased risk for death and graft loss among low MELD–low BMI patients after LT. Thus, our work presents compelling data to suggest that measures of malnourishment, sarcopenia, and functional status are important assessments to be made in low MELD, low BMI patients.

Safety and Outcomes in 100 Consecutive Donation After Circulatory Death Liver Transplants Using a Protocol That Includes Thrombolytic Therapy.

Richard B. Freeman Jr., Robert G. Gish, Ann Harper, Gary L. Davis, John Vierling, Leslie Lieblein, Goran Klintmalm, Jamie Blazek, Robert Hunter, and Jeffrey Punch Division of Transplantation, Department of Surgery, Tufts–New England Medical Center, Boston, MA; Departments of Medicine and Transplantation and the Division of Hepatology and Complex GI, Physicians Foundation, California Pacific Medical Center, San Francisco, CA; United Network for Organ Sharing, Richmond, VA; Baylor Regional Transplant Institute, Baylor University Medical Center, Dallas, TX; Department of Medicine, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA; Ochsner Multi-Organ Transplant Center, New Orleans, LA; and Department of Surgery, University of Michigan, Ann Arbor, MI

Cystatin C (CysC) is an early biomarker of renal dysfunction scarcely studied in patients awaiting liver transplantation (LT). Sarcopenia is frequent in cirrhosis and impacts prognosis. We aimed to assess the capability of these factors to predict survival and acute-on-chronic liver failure (ACLF) in patients awaiting LT, as well as early post-LT outcomes. Single-center study that included all cirrhotic patients listed for LT between 2014 and 2017. Competing risk regression analysis was used to evaluate the capability of liver-, kidney-, and global status-related variables at waitlist (WL) inclusion to predict WL mortality and ACLF. Variables associated with post-LT outcomes were evaluated with logistic regression analysis. One-hundred-and-eighty patients were included. Fifty-six (31%) patients developed ACLF, 54 (30%) underwent LT and 35 (19%) died. In the adjusted competing risk regression analysis, CysC ≥ 1.5 mg/L, sarcopenia and MELD-Na were independent predictors of ACLF in the WL, while CysC ≥ 1.5 mg/L, sarcopenia and albumin were independent predictors of mortality. The cumulative incidence of ACLF and mortality at 12 months were 50% and 34% in patients with sarcopenia and CysC ≥1.5 mg/L. An estimated glomerular filtration rate by chronic kidney disease (CKD)-EPI-CysC-creatinine <60 mL/min/1.73 m at WL inclusion was an independent predictor of the need for renal replacement therapy (RRT) in the first month post-LT. Higher levels of CysC and sarcopenia are strongly associated with the ACLF and mortality in WL. The assessment of both risk factors may improve the prognostic evaluation and allow identifying a group of patients with a very high risk of poor outcomes while awaiting LT.

In the early 1980s, organ allocation in the United States was initially based on anecdotal experience, self-interest, and single-center opinions with little in the way of scientific evidence, mathematical survival modeling, or validation to support these patterns of organ allocation. As liver transplantation (LT) became more successful, the disparity between the number of patients on the waiting list and available donor organs became an issue as a result of increasing wait-list deaths, and thus, a more justifiable donor organ allocation scheme became necessary. An initial attempt at establishing organ allocation policy came in 1987 when the U.S. government established the Organ Procurement and Transplantation Network as part of the Transplantation Act. The Organ Procurement Transplantation Network operates under federal contract with the United Network for Organ Sharing (UNOS). Since the formation of the Organ Procurement Transplantation Network, attempts to improve and standardize organ allocation have been ongoing and evolving. LT, liver transplantation; UNOS, United Network for Organ Sharing; MELD, Model for End-Stage Liver Disease; PELD, Pediatric End-Stage Liver Disease; HCC, hepatocellular carcinoma; MESSAGE, MELD Exceptional Case Study Group. Liver allocation policy was initially based on patients' location of care. Patients requiring continuous intensive care, including patients with acute esophageal variceal bleeding not responding to endoscopic therapy; patients who developed hepatorenal syndrome; and patients with intractable ascites or intubated with stage 4 portosystemic encephalopathy received first priority. Organ allocation was prioritized next to patients requiring continuous hospitalization, and finally to patients who were cared for at home.1 However, as the waiting list continued to grow, waiting time became a major factor in determining who received a donor organ. Before February 2002, liver allocation was prioritized according to 4 UNOS-defined categories: status 1, 2A, 2B, and 3. These categories were based on whether the patient required admission to an intensive care unit and on the patient's Child-Turcotte-Pugh score.2 One problem with this scheme was that there were no established criteria for defining which patients truly required intensive care unit admission, thus allowing less ill patients to remain in the intensive care unit and gain an advantage for liver organ allocation. Furthermore, there were large numbers of patients in each of the 4 UNOS listing strata, and deaths on the waiting list continued to increase. Consequently, waiting time became the tiebreaker and the ultimate major determinant of organ allocation in the United States. However, as demonstrated by Freeman and others,3, 4 waiting list mortality did not correlate with waiting time. As a result of these disparities, the Department of Health and Human Services issued its Final Rule mandate in 1998 stating that donor livers should be allocated according to medical urgency and that a more continuous system should be used as mentioned by the Institute of Medicine.5, 6 In response to the Department of Health and Human Services mandate, UNOS formed the Liver Allocation Committee, and in February 2002, the Model for End-Stage Liver Disease (MELD) was adapted for the allocation of donor livers in the United States. The MELD score was initially developed to predict mortality in patients receiving transjugular intrahepatic portosystemic shunts to treat variceal bleeding or resistant ascites. The initial model, called the Mayo Model for End-Stage Liver Disease, consisted of 3 objective variables: serum creatinine, serum total bilirubin, international normalized ratio, and a fourth variable based on liver disease etiology.7 During further assessment, the name was changed to the MELD scoring system, and investigators found that etiology contributed minimally to predicting short-term survival. Thus, the final MELD model used for liver allocation policy is based on serum creatinine, serum total bilirubin, and international normalized ratio. The MELD score has been retrospectively and prospectively shown to be highly predictive of short-term mortality in patients with all causes of end-stage liver disease who are awaiting LT.8 The model has been validated for prediction of 3-month and 1-year mortality (and inversely survival) in a broad spectrum of patients with chronic liver disease.9 The advantages of the MELD system for organ allocation are that all variables are objective and statistically weighted, and the model has a continuous scale with no ceiling or floor effects, thereby reducing a large number of ties (multiple patients with equal waiting times) and virtually eliminating dependence on waiting time for ranking candidates except as a tiebreaker for patients with equal MELD scores. Since the implementation of MELD system, assessment of the UNOS liver allocation policy has revealed marked changes in the dynamics of organ allocation.10 The mean MELD score at transplantation increased from 17 in the pre-MELD era to 22 in the post-MELD era. Despite a shift to sicker patients receiving transplants, there have been no differences in 1-year patient and graft survival rates since implementation of the MELD system. And there has been a reduction in median waiting time from 656 days to 416 days. The major reason for the reduction in waiting time has been the removal of waiting as a criterion for liver offer. Thus, the most ill patients receive an offer first, regardless of how long they have waited. This also removed the incentive to "list patients early" to gain waiting time at a time when their liver disease was not very severe. Perhaps the most important indicator of the superiority of the MELD system over the previous allocation system was a reduction in waiting list mortality by 3.5% after its implementation. These changes clearly met the requirements of the Department of Health and Human Services, which state that organs should be allocated on the basis of medical urgency rather than waiting time. However, at the time the MELD liver allocation system was implemented, policy makers recognized that not all LT candidates benefited from LT because they faced a high risk of dying from their intrinsic liver disease. These patients would not have their need for LT accurately characterized by their calculated MELD or Pediatric End-Stage Liver Disease (PELD) score.11 Hepatocellular carcinoma (HCC) is one such example. Rule makers defined the need for LT for these candidates as the risk of progressing beyond tumors meeting the so-called Milan criteria, a stage at which excellent posttransplant results could be achieved.12 At the initial time of MELD and PELD policy implementation, there were no good data quantifying the risk of HCC progression, so estimates of probability were arbitrarily assigned and equated to the MELD-defined probability of death, resulting in awarding of additional MELD points to the calculated MELD scores.11 Thus, with additional points, the initial assessment of the MELD allocation system demonstrated that there was a reduction from 24 to 7% in patients with HCC falling off the waiting list.13 Subsequently, many studies have examined the progression of HCC in waiting LT candidates,14 and the HCC prioritization policy has been revised several times. There are patients with other conditions for which the need for LT is not accurately defined by the MELD score because their prognoses depend on factors other than liver disease mortality risk.15 As such, these patients have potential for being underserved (wait list removals or death) if they are ranked for allocation of deceased donor livers solely on the basis of a calculated MELD score derived from their pretransplant laboratory values. Some of these conditions, in addition to HCC, such as the progressive pulmonary compromise seen in hepatopulmonary syndrome, familial amyloid polyneuropathy, metabolic liver diseases such as urea cycle defects or hereditary oxaluria, have been identified and termed the so called "exceptional diagnoses."16 In addition, because the MELD/PELD score accurately predicts death from liver disease in approximately 80 to 85% of patients, as many as 15 to 20% of patients with chronic liver disease may not be accurately prioritized by their MELD/PELD score. It was recognized that it is unlikely that any scoring system would serve all potential LT candidates equally well, and for these reasons, the original MELD allocation policy included a mechanism by which centers could request increased priority for any patient for whom the MELD/PELD score was thought to inaccurately estimate their need for LT. The policy stipulated that these requests would be reviewed by a regional peer review system to determine the appropriateness of the requested increase in priority on the basis of medical evidence from the literature or expert opinion. The goals behind allowing certain disease entities to receive increased priority on the waiting list as MELD exceptions are severalfold: (1) decrease patient risk of death on the waiting list; (2) increase timeliness of LT before the underlying liver disease progresses to the point that the patient can no longer be considered a LT candidate; (3) decrease the risk of disease of recurrence after LT; (4) prevent disease progression that is dependent on a metabolic or genetic disease that may preclude LT, and (5) improve survival after LT. With the exception of HCC, however, MELD-equated priority guidelines were not identified for these other exceptional diseases. After the first year of use of the MELD allocation policy, Rodriguez-Luna and collagues17 assessed Regional Review Board practices. They found that large variations existed throughout the country in how exceptional cases were handled. Because these differences exist and there are no guidelines available for the consistent assessment of exceptional case applications other than for HCC, UNOS convened a study group, MELD Exceptional Case Study Group (MESSAGE), a subcommittee of the UNOS Liver and Intestinal Committee, to develop a consensus and to advance the field and provide written recommendations to UNOS, the Liver and Intestinal Committee within UNOS, and guidelines to the Regional Review Boards to aid in the assignment or denial of assignment of MELD score upgrades. Thus, the goals of MESSAGE and the conference were to make evidence-based recommendations when possible and create a uniform approach to a number of conditions that were believed to be underserved when the calculated MELD score was used. The MESSAGE group, with the assistance of the Scientific Registry of Transplant recipients and UNOS, identified 17 diagnoses or groups of diagnoses for which MELD exceptions were requested for Regional Review Board deliberation. The members of this committee reviewed the literature for evidence or expert opinion to support or refute the validity of waiting list death, waiting list removals for progressive disease, waiting list removals as too ill, and evidence of nonhepatic end-organ injury that would obviate LT for patients with these diagnoses and determine if these patients with specific diagnoses should receive increased waiting-list priority. These findings were presented at a national conference held in Chicago, March 1 to 2, 2006, where final recommendations were reached. The MESSAGE committee members and the members of the Liver and Intestinal Committee who were involved in this project emphasize that the Regional Review Boards across the country have held widely divergent opinions on which conditions should receive additional MELD points, if any, and on how much priority should be given for exceptional case requests. The purpose of the MESSAGE group's work was to provide a consistent, evidence-based approach for listing patients with additional MELD points across the liver transplant programs and regions within the UNOS. This series of articles summarize MESSAGE's deliberations and conclusions reached at this conference.

See Article on Page 1011

Strategies for liver transplantation during the SARS-CoV-2 outbreak: Preliminary experience from a single center in France.