Liver Transplantation in Croatia: "David Among Goliaths".

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

Evidence-Based Incorporation of Serum Sodium Concentration Into MELD

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

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.

The impact of the COVID-19 outbreak on liver transplantation programs in Northern Italy.

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

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

You celebrated 6000 liver transplants at UCLA in 2016. How does one build the largest liver transplant program in the world?FigureRWB: The building of our Liver Transplantation Program at UCLA, was a complex undertaking stimulated by a 20-year-old patient whom I had performed a distal splenorenal shunt for variceal bleeding. Unexpectedly, he developed liver failure 7 days postoperatively and died, before I could transfer him to Dr. Starzl in Pittsburgh for consideration of liver transplantation. As I walked out of the ICU that day, I turned to my friend and hepatology colleague, Dr. Leonard Goldstein and stated “Leonard, we need to start doing liver transplants at UCLA.” In late 1982, I told Dr. William P. Longmire, Jr., a renowned liver surgeon and Chairman at UCLA, that I would like to start a liver transplant program. He was supportive, and I assembled a team and initiated a program of porcine orthotopic liver transplantation. We performed over 50 transplants using venous-venous bypass, with excellent success. I then visited Dr. Starzl in Pittsburgh to observe clinical liver transplantation and participated in about 6 cases. Over the next several months, we put together our multidisciplinary team at UCLA despite some skepticism from hospital administration. On February 1, 1984, we performed our first liver transplant on a recipient with a hepatic schwannoma and used venous venous bypass. The patient required 17 units of blood and was discharged on postoperative day 17. We performed our 100th liver transplant at UCLA in November 1986, and reported our experience the following year at the American Surgical Association. In my closing remarks, I recognized Dr. Starzl’s contributions: “how well I remember the multiple phone conversations on our first few transplants, in which I sought your advice, encouragement and leadership and I am very grateful for that.” After our first 100 liver transplants, our program continued to grow rapidly since we were one of the first programs in the western part of the United States, and encompassed the entire spectrum of pediatric and adult liver transplantation including the sickest patients. Our team performed our 5000th liver transplant on September 9, 2010, and our 6000th on June 30, 2016, making our program one of the largest worldwide. None of this could have happened without the unfailing support of our totally dedicated multidisciplinary team of surgical and medical specialists, nurse coordinators, hospital leadership, administrators, organ procurement agency, and the supportive generosity of donor families. More than 6000 liver transplants would not go by without remembering very special cases. What is your most memorable surgery and patient? RWB: To be honest, all of my patients are memorable. Certainly, those who did not survive have influenced me in ways that resulted in improving our patient and donor selection, operative techniques and postoperative management. If we look for instance at our pediatric patients there has been a significant improvement in 15 year graft survival from 51% from 1984 to 2000 to 72% from 2001 to 2017. Although all of my patients are memorable, there is a very special 1-year-old child, who I transplanted on August 8, 1984, our fifth transplant, with a giant hepatic hemangioendothelioma who is now 34 years old, married, and living a wonderful life. She is one of over 1000 children that we have transplanted in our program. In addition to excellent clinical outcomes, you have a unique collection of clinical data. How did you built your database and what have you learnt and brought back to clinical application? RWB: From the inception of our program, each patient evaluated for liver transplantation has been registered into an IRB sanctioned transplant database, with a comprehensive list of recipient, donor, and perioperative variables maintained prospectively. Over the years, our transplant surgeons have played the leading role in extracting additional clinical, laboratory, radiologic, and pathologic information from the medical records, resulting in the continuous growth and enrichment of the database which is updated regularly. This robust research database has been integral to our research productivity over the years. With greater than 800 publications in peer-reviewed journals, the UCLA transplant program has made significant contributions to the field of liver transplantation, with leading roles in numerous randomized-controlled trials that led to the current standard of care in immunosuppression (tacrolimus), and fungal, viral, and PCP prophylaxis following LT. Furthermore, we have contributed important innovations in surgical techniques such as in situ split-liver transplantation, as well as innumerable reports of clinical outcomes examining salient issues pertaining to donor allocation, use of extended-criteria donor allografts, and transplantation for malignancies. Our clinical research program is integrated with our robust basic science and translational program focusing on hepatic ischemia/reperfusion injury, leading to several clinical trials in human liver transplantation. You have mentored many transplant surgeons who went on to take very successful leadership roles. What is the secret of your mentoring style? RWB: I truly believe that one of the most important components of my career has been my commitment to training and mentoring future leaders in transplantation. This is a multifaceted commitment, and as stated by Gary Burnison, CEO of Korn Ferry International, “to lead is to be all in, transparent and accessible, calm in the face of upset and even crisis, and always mindful that you are a steward of something bigger than yourself.” Transplantation is certainly a discipline which demands all of the above. Additionally, to be successful in training our future leaders, you must demonstrate vision, self-direction, courage to take on complex cases, and most importantly to always embody honesty and integrity. Finally, genuine, personal interaction is essential. Despite my administrative role as Chairman of our Department, I always set time aside for personal interaction and the mentoring of medical students, residents and fellows, which includes clinical rounding, one-on-one meetings, and hosting a monthly Journal Club at my house for the last 30 years. The LA Times had an interview, now almost 2 decades back in which they featured you and your efforts in finding novel ways to keep up with the demand for liver transplantation. All those attempts, at the time seemed unable to keep up with havoc caused by hepatitis C. Today, new and effective antivirals have changed the game. How have the new antivirals changed liver transplantation? RWB: Hepatitis C was clearly the most common indication for liver transplantation in most centers in the United States until the advent of effective antiviral agents over the past couple of years. However, even patients who have cleared the virus may still require liver replacement due to failing liver function. In these cases, the results of liver transplant are vastly improved due to the lack of HCV recurrence. HCV is diminishing as an indication for liver transplant, and we now have a new leader in the queue, which is nonalcoholic steatohepatitis (NASH). In many cases, these patients are more complex, more technically demanding and have additional co-morbidity. We are pushing to establish a trial to determine if sleeve gastrectomy performed with liver transplantation will improve the outcomes of these difficult patients. There has been a long debate on the timing for patients with end-stage alcohol toxic liver disease. Is it safe to transplant those patients without a minimum time of documented abstinence? RWB: Liver transplantation for alcoholic hepatitis is a very controversial topic, due to the high rate of recidivism and the limited donor pool. However, there is more data coming out which shows that early liver transplantation for severe alcoholic hepatitis in selected patients can provide very good short-term survival and equivalent rates of relapse as seen in patients who have 6 months of abstinence pretransplant. One of my former fellows, Dr. Andrew Cameron, Chief of Liver Transplantation at Johns Hopkins University, recently published the results of a 3-year pilot program comparing patients with alcoholic hepatitis after first liver decompensation versus those with the same condition that had 6 months of abstinence. The survival and incidence of alcohol relapse was the same in both groups. In an editorial that I authored for this article, I concluded that the dramatic improvement in survival in those transplanted early and the equivalent recidivism rates compared to those transplanted after 6 months sobriety justifies this approach and careful consideration should be given to implementing this policy with close scrutiny. You list more than 700 publications in PubMed. What do you consider your most important scientific contribution? Together with Dr. Jerzy Kupiec-Weglinski you have explored many novel mechanistic and therapeutic avenues addressing ischemia/reperfusion injury. What of those efforts have been or about to be translated into clinical application? RWB: I have been intensively involved in both clinical and basic science research since I was a medical student at Tulane, where I obtained my MD and MS degrees. My masters degree thesis was “The Cytological Localization of Erythropoietin Using the Fluorescent Antibody Technique”. Upon obtaining my PhD in 1975, I published one of the first articles demonstrating that steroid therapy was successful in blocking ischemia reperfusion injury in ischemic hearts. Since founding the liver transplant program in 1984, my basic research program has been focused on the prevention of ischemia reperfusion injury (IRI) of the liver. I have been continually funded from the NIH and other peer-reviewed granting agencies since 1981. In 1997, I recruited Jerzy Kupiec-Weglinski, MD, PhD, from Harvard University to lead the basic science thrust of our laboratory. I have worked very closely with Dr. Kupiec-Weglinski to specifically identify the mechanisms of (IRI) and to develop treatment modalities to prevent the injury. Indeed, our “bench-to-bedside” collaborative research on the innate—adaptive immune interface in liver transplant recipients has been recently awarded a 5-year Program Project Grant from the NIH. As there are less than 10 program project grants in the country funded by the NIH that are related to organ transplantation, this is quite an achievement. The focus of the research on liver ischemia reperfusion injury (IRI) is both basic and translational since IRI contributes to poor graft function after transplantation. Minimizing the adverse effects of IRI could increase the number of patients that may successfully undergo liver transplantation. Our research has involved studying the platelet leukocyte endothelial cell interactions which play a central role in IRI. We were the first group to document that inhibition of P-Selectin activation by blocking P-Selectin glycoprotein ligand-1 was highly successful in increasing survival in marginal liver grafts after transplantation. I have been the principal investigator of these studies since they were initiated in the mid-1990s and currently these have been expanded to the clinical arena with Phase II clinical trials utilizing P-Selectin/PSGL-1 blockade in both kidney and liver transplantation. In 2012, I was the lead author of a randomized placebo controlled phase II clinical trial comparing placebo versus selectin blockade in a series of 47 patients undergoing liver transplantation. Selectin blockade proved to be nontoxic and improved graft survival, liver function tests and biomarkers of inhibition of IRI. This study is the stimulus for a multicenter trial investigating selectin blockade as a mechanism to improve liver graft function and has applicability to other organ transplants. In addition to this basic science research, I have been the senior author on numerous seminal clinical articles which have served as benchmarks in the treatment of liver transplant patients in many areas of clinical focus including: immunosuppression, perioperative viral and fungal prophylaxis, technical modifications, use of extended criteria donors, management of infants undergoing liver transplantation, hepatocellular carcinoma, living donor organ donation, split liver transplantation, combined kidney - liver transplants, multivisceral transplants, and transplantation of patients with the highest Model for End-stage Liver Disease score, which is used to allocate organs. Many of these accomplishments were supported by NIH and other peer-reviewed funding. Looking into the future: what do you see as the main challenges for liver transplantation in the 10 years? RWB: There are indeed numerous challenges for liver transplantation that we will encounter over the next 10 years. Today, liver transplantation is considered the gold standard for treatment of patients with end-stage liver disease. However, new improved treatment strategies, as we now have for HCV and HBV, and in the possible near future for hepatocellular carcinoma will surely decrease the need for liver replacement. In certain metabolic diseases, cellular transplantation may become very effective as the preferred treatment over whole organs. Life-long immunosuppression definitely has its drawbacks. However, once our ability to induce tolerance improves, immunosuppressive drug therapy will be minimized. Furthermore, the new avenues of research such as blockade of ischemia reperfusion injury and the resuscitation of marginal grafts with novel preservation concepts will significantly increase the organ donor pool. Your energy does not seem to stop outside of the hospital walls. There are rumors that a unique collection of Italian sport cars share your home address. Moreover, you are an avid runner and have finished the new your city marathon twice. What do you enjoy outside the operating room? RWB: My career would not have developed were it not for the incredible, selfless, and loving support of my family: my wife of 50 years, JoAnn, our 2 daughters, Amber and Ashley, and my 4 grandsons. One of my passions is indeed automobiles, perhaps a genetic trait inherited from my father, who was a car dealer when I was growing up. I worked in his dealership as a teenager and attended many races including the 12 hours of Sebring, the Monte Carlo Grand Prix, and the Indianapolis 500. I personally raced in the Mille Miglia 1000-mile race in Italy 3 times. I have been playing tennis since I was a medical student, and still exercise daily with a morning or evening run depending on my OR and administrative schedule. My wife, JoAnn is an art enthusiast, collector, and docent for the Los Angeles Museum of Art, and I have enjoyed and benefited from her expertise and passion in this area for many years.

We sought to evaluate the impact of liver transplantation (LT) programs on the prognosis of hepatocellular carcinoma (HCC) patients who underwent liver resection (LR) and noncurative intent treatment. LT programs have an array of resources and services that would positively affect the prognosis of patients with HCC. Patients who underwent LT, LR, radiotherapy (RT), or chemotherapy (CTx) for HCC between 2004 and 2018 were included in the National Cancer Database. Institutions with LT programs were defined as those that performed 1 or more LT for at least 5 years. Centers were stratified by hospital volume. The impact of LT programs was assessed after propensity score matching to achieve covariate balance. A total of 71,735 patients were identified, of which 7997 received LT (11.1%), 12,683 LR (17.7%), 15,675 RT (21.9%), and 35,380 CTx (49.3%). Among a total of 1267 distinct institutions, 94 (7.4%) were categorized as LT programs. Designation as an LT program was also associated with a high volume of LR and noncurative intent treatment (both P <0.001). After propensity score matching, LT programs were associated with better survival among LR and noncurative intent treatment patients. Although hospital volume was also associated with improved prognosis, LT programs were associated with additional survival benefits in noncurative intent treatment. On the other hand, no such benefit was noted in patients who underwent LR. The presence of an LT program was associated with a higher volume of LR and noncurative intent treatment. Furthermore, designation as an LT program had a "halo effect" on the prognosis of patients undergoing RT/CTx that went beyond the procedure-volume effect.

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

Child, MELD, hyponatremia, and now portal pressure

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

Should donors and recipients be matched in liver transplantation?

New organ allocation policy in liver transplantation in the United States.

The idea that matching donor and recipient features ought to be a reasonable allocation policy is increasing among liver transplant programs, in particular in the era of extended-use donors (1–3). The best survival gain with a liver transplant (LT) may be achieved by allocating livers to patients who are most likely to be dropped from the list without a LT, but who also have the highest probability of survival after LT (3). The greatest transplant benefit may therefore be achieved by selecting the recipients on the waiting list and selecting the recipients according to the donors available. The study recently published by our Center in the February issue of Transplantation showed how we managed the risk of drop-out due to tumor progression of patients with hepatocellular carcinoma (HCC) in the pre–Model for End-Stage Liver Disease (MELD) era. The old donors were more frequently allocated to patients with HCC and following this policy we reduced the drop-out rate of HCC patients and we improved the survival of marginal grafts after LT (4). The present study validated the idea that the match between the donor and recipient features improves the liver allocation policy. On the other hand, as commented by Lucey (5), we do agree that these data should not be contrasted with the MELD allocation policy and we believe that the next issue will be how to allocate extended-use donors in the MELD era. As reported in the United States, the MELD system provides the best selection of the recipients at the highest risk of dying on the waiting list (6). This policy has also been applied in our Center since March 2003 and after two years of experience, we significantly improved the patient survival on the waiting list (7). We consequently believe that the selection of patients on the waiting list according to their MELD score improves the survival on the waiting list and it is a reasonable method of sharing livers between different transplant programs. On the other hand, as stressed by Lucey, the weak aspect of this policy is that it does not consider the donor features: not all donors are appropriate for all recipients. An extended-use donor may work properly in one recipient and it may not work in another. The challenge is therefore to calculate the ideal match between the donor and recipient features, which may offer the highest transplant benefit. In the MELD era this policy could be applied, but we need to know the transplant benefit that every graft may give to every recipient. When this data is available, we will select the recipient on the waiting list not only considering the recipient’s MELD score, but also evaluating the survival gain that the graft could offer to the patient. An extended-use donor could therefore be allocated not to the first recipient on the waiting list, but to the second or third one, if they were presumed to have the highest transplant benefit. A simple example is reported in Table 1. The transplant benefit depends on the risk of drop-out on the waiting list and on the risk of death after LT. These two variables are center-dependent (8–9), but a relevant role on the outcome of the patients on the waiting list and after LT is due to the recipient and donor’s clinical features and to the match between recipients and donors. In conclusion, our future effort to further improve the liver allocation system is to produce a calculated risk of death after LT for each category of recipients and for each category of donors, which should be compared to the risk of death on the waiting list.