Liver transplantation of living donor adult-to-adult

End-stage liver disease is being treated by liver transplantation since more than 20 years. Despite social and legislative efforts, the number of cadaveric organs suitable for liver transplantation has not grown to match the surplus of patients with end-stage liver disease. With the growing discrepancy between donors and recipients, the median waiting time for liver transplantation has increased dramatically. As a result, the number of patients who die while waiting is increasing. To attempt to meet the growing needs of recipients, surgeons are developing innovative techniques to increase the number of donated livers. These include: split liver transplantation and transplantation of a part of the liver from living donors. This review will focus on adult-to-adult transplantation of the right lobe from a living donor.     

A clinically based discrete-event simulation of end-stage liver disease and the organ allocation process.

BACKGROUND: The optimal allocation of scarce donor livers is a contentious health care issue requiring careful analysis. The objective of this article was to design a biologically based discrete-event simulation to test proposed changes in allocation policies. METHODS: The authors used data from multiple sources to simulate end-stage liver disease and the complex allocation system. To validate the model, they compared simulation output with historical data. RESULTS: Simulation outcomes were within 1% to 2% of actual results for measures such as new candidates, donated livers, and transplants by year. The model overestimated the yearly size of the waiting list by 5% in the last year of the simulation and the total number of pretransplant deaths by 10%. CONCLUSION: The authors created a discrete-event simulation model that represents the biology of end-stage liver disease and the health care organization of transplantation in the United States.     

Liver transplant allocation policies and outcomes in United States: A comprehensive review

Liver transplant allocation policies in the United States has evolved over 3 decades. The donor liver organs are matched, allocated and procured by the Organ Procurement and Transplantation Network which is administered by the United Network of Organ Sharing (UNOS), a not-for-profit organization governed by the United States human health services. We reviewed the evolution of liver transplant allocation policies. Prior to 2002, UNOS used Child-Turcotte-Pugh score to list and stratify patients for liver transplantation (LT). After 2002, UNOS changed its allocation policy based on model for end-stage liver disease (MELD) score. The serum sodium is the independent indicator of mortality risk in patients with chronic liver disease. The priority assignment of MELD-sodium score resulted in LT and prevented mortality on waitlist. MELD-Sodium score was implemented for liver allocation policy in 2016. Prior to the current and most recent policy, livers from adult donors were matched first to the status 1A/1B patients located within the boundaries of the UNOS regions and donor-service areas (DSA). We reviewed the disadvantages of the DSA-based allocation policies and the advantages of the newest acuity circle allocation model. We then reviewed the standard and non-standard indications for MELD exceptions and the decision-making process of the National Review Liver Review Board. Finally, we reviewed the liver transplant waitlist, donation and survival outcomes in the United States.     

An evaluation of the model for end-stage liver disease and serum C-reactive protein as prognostic markers in intestinal failure patients on parenteral nutrition

Background: Intestinal failure (IF) patients require parenteral nutrition (PN) to avoid malnutrition and death. However, they face complications of recurrent sepsis and liver failure. By the time liver failure is discovered, it is often too late for intervention and prognosis on the waiting list is grim. The Model for End‐Stage Liver Disease (MELD) has traditionally been used to predict mortality in patients with liver failure but has never been analyzed in IF patients who are at risk for liver complications. C‐reactive protein (CRP) is an acute inflammatory marker that has been shown to reflect disease progression in nonalcoholic steatohepatitis, a disease that in many ways resembles PN‐associated liver disease. MELD and CRP are promising clinical markers of disease progression in IF patients on PN. Methods: The authors performed a retrospective, case‐control study to compare levels of MELD and CRP within the entire population of 133 adult patients referred to Northwestern Memorial Hospital for IF from 1999 to 2006. Results: Elevated MELD score is strongly predictive of increased mortality over the subsequent 6 months. Elevated CRP is strongly predictive over a smaller 3‐month window. One‐year mortality was significantly greater in patients who have either elevated MELD scores or serum CRP levels. Conclusions: In this study, the authors evaluated for the first time use of MELD and serum CRP as predictive markers of mortality in IF patients. Both seem to be promising clinical tools to identify which patients are at highest risk for complication.     

Assessing emerging technologies--the case of organ replacement technologies: volume, durability, cost

OBJECTIVES: The aim of this study was to estimate thresholds for production volume, durability, and cost of care for the cost-effective adoption of liver organ replacement technologies (ORTs). METHODS: We constructed a discrete-event simulation model of the liver allocation system in the United States. The model was calibrated against UNOS data (1994-2000). Into this model, we introduced ORTs with varying durability (time to failure), cost of care, and production volume. Primary outputs of interest were time to 5 percent reduction in the waiting list and time to 5 percent increase in expected transplant volume. RESULTS: Model output for both calibration and validation phases closely matched published data: waiting list length (+/-2 percent), number of transplants (+/-2 percent), deaths while waiting (+/-5 percent), and time to transplant (+/-11 percent). Reducing the waiting list was dependent on both ORT durability and production volume. The longer the durability, the less production volume needed to reduce the waiting list and vice versa. However, below 250 ORT/year, durability needed to be >2 years for any significant change to be seen in the waiting list. For base-case costs, all ORT production volume and durability scenarios result in more transplants per year at less total cost of care/patient than the current system. ORTs remain cost saving until manufacturing costs are >5 times base-case costs, production is less 500 ORT/year, and durability <6 months. CONCLUSIONS: Although there remain many technical challenges to overcome, as long as ORTs can meet these threshold criteria, they have the potential of transforming the world of end-stage liver disease.     

A Simulation Modelling Approach to Evaluating Alternative Policies for the Management of the Waiting List for Liver Transplantation

A shortage of donor liver grafts unfortunately results in approximately 10% of patients dying whilst listed for a liver transplant in Europe and the United States. Thus it is imperative that all available organs are used as efficiently as possible. This paper reports upon the application of a simulation modelling approach to assess the impact of several alternative allocation policies upon the cost effectiveness of this technology at one liver transplant centre in the UK. The impact of changes in allocation criteria on the estimated net life expectancy, average net costs and overall cost effectiveness of the transplantation programme were evaluated. The incremental cost effectiveness ratio (ICER) for the base case allocation policy, based upon the time spent on the waiting list (i.e., longest wait first) was £11,557 at 1999 prices. The ICERs associated with an allocation policy based upon age (lowest age first), and an allocation policy based upon the severity of the pre-transplant condition of the patient (with most severely ill patients given a lower priority) were lower than the base case at £10,424 and £9077, respectively. The results of this modelling study suggest that the overall cost effectiveness of the liver transplantation programme could be improved if the current allocation policy were modified to give more weight to the age of the patient and the reduced chances of success of the most severely ill patients.     

Unequal access to cadaveric kidney transplantation in California based on insurance status.

OBJECTIVE: To assess the impact of insurance status on access to kidney transplantation among California dialysis patients. STUDY SETTING: California Medicare and Medicaid dialysis populations. STUDY DESIGN: All California ESRD dialysis patients under age 65 eligible for Medicare or Medicaid in 1991 (n = 9,102) took part in this cohort analytic study. DATA COLLECTION: Medicare and California Medicaid Program data were matched to the Organ Procurement and Transplantation Network Kidney Wait List files. PRINCIPAL FINDINGS: Only 31.4 percent of California Medicaid dialysis patients were placed on the kidney transplant waiting list compared to 38.8 percent and 45.0 percent of dually eligible Medicate/Medicaid and Medicare patients, respectively. Compared to the Medicaid population, Medicare enrollees were more likely to be placed on the kidney transplant waiting list (adjusted Relative Risk [RR] = 2.10, Confidence Interval [CI] 1.68, 2.62) as were dually eligible patients (RR = 1.54, CI 1.24, 1.91). Once on the waiting list, however, Medicare enrollment did not influence the adjusted median waiting time to acquire a first cadaveric transplant (p > .05). CONCLUSIONS: California dialysis patients excluded from Medicare coverage, who are disproportionately minority, female, and poor, are much less likely to enter the U.S. transplant system. We hypothesize that patient concerns with potential subsequent loss of insurance coverage as well as cultural and educational barriers are possible explanatory factors. Once in the system, however, insurance status does not influence receipt of a cadaveric renal transplant.     

Recipient selection for liver transplantation

In the last few years, there have been developments in many aspects of liver transplantation. Improvements in surgical techniques and immunosuppression markedly increased the success rates of liver transplantation. This success has lead to increasing numbers of recipients. However, the availability of cadaveric organs for transplantation has not been changed in the last 10 years, resulting in a growing discrepancy between donors and recipients. Thus, it is necessary to properly select the best candidates for a successful liver transplant. This article will review the indications and contraindications for liver transplantation in the Model for End Stage Liver Disease (MELD) score era.     

Weights for waits: lessons from Salisbury

OBJECTIVES: This paper describes a waiting list patients' points scheme under development in Salisbury, UK, for the fair management of elective inpatient and day case waiting lists. The paper illustrates how points can be assigned to patients on a waiting list to indicate their relative unmet need, and illustrates the impact on case mix and resource use of the implementations of the points system versus 'first come, first served'. The paper explores a range of philosophical and technical questions raised by the points system. METHODS: The Salisbury Priority Scoring System enables surgeons to assign relative priority to patients at the time they are placed on a waiting list for elective health care. Points are assigned to patients to reflect the rate of progress of their disease, pain or distress, disability or dependence on others, loss of usual occupation and time already waited. In recognition of the need for resource planning alongside the prioritization of elective inpatients and day case waiting lists, a range of iso-resource groups has been developed for all procedures on these lists. These categorize procedures in terms of their resource use (i.e. bed days and theatre time required). RESULTS: In a modelling exercise, application of the Salisbury Points Scheme to a 'first come, first served' orthopaedic waiting list produced considerable changes in the order of patients to be treated. Only seven patients appeared in the first 20 patients to be treated under both regimes. The Salisbury Scheme required fewer resources to treat its first 20 patients than 'first come, first served' and met more Salisbury-defined 'need', but eliminated fewer days of waiting from the list. CONCLUSIONS: Development of a points scheme and iso-resource groupings opens up opportunities for more sophisticated purchasing, based on treating patients in order of unmet need rather than according to arbitrary maximum waiting time guarantees, as has been the dominant policy on waiting lists pursued in the UK, Australia, and Sweden, to date. However, such schemes raise three issues: first, the necessity of defining need as a composite of clinical and social factors; second the necessity to determine the acceptability of explicit prioritization to both health care professionals and patients; third, the thorny issue of whether such prioritization schemes will lead to 'gaming' by well-meaning general practitioners and specialists, aiming to secure the priority of their own patients and clinical specialty. Rigorous piloting of schemes, such as that developed at Salisbury, will be required to identify their dynamic effect over time on case mix, waiting time and resource use.     

Problems of priority change in kidney allocation and beyond

Standardized and transparent priority setting in medicine, desirable as it is, will generally exacerbate inter-temporal equity problems arising from changes in treatment priorities: when can it be fair that the treatment of already waiting patients who would have had priority under an established system should be postponed (withheld) for an extended period of time to advance the treatment of others under a reformed system? The reform of the Eurotransplant system of priority setting in kidney allocation (ETKAS), which is in many respects ideal, is a case in point. To give due weight to new medical knowledge, waiting time after the onset of end state renal failure should change from a priority-enhancing to a priority-reducing factor. Since those who have gained in priority by waiting under the present system would be set back under the new, severe problems of transitional justice must be overcome when responding to advances in medical knowledge. The paper explores conceptually some possible ways of rule change and indicates their general relevance from an ethical and a practical point of view for future problems of medical resource allocation under transparent, standardized priority-setting rules.     

Waiting lists for transplantation in Italy

To plan health services it is essential to gauge the needs. In transplant field in Italy, the first suitable data for waiting lists were collected in 1998. The data collected by Istituto Superiore di Sanità gave us a shot of patients field in waiting list at that time. We here analyse more significant data about heart, liver and kidney waiting lists. The situation is very different among north, centre and south of Italy: in South, where transplant activity is low, we found rare transplant centres, and most of patients prefer north centres. In kidney waiting list we found 1100 patients living in southern regions but registered in the waiting list of a different region. These data can help in planning development lines in Italy.     

Variations in clinical decisions: a study of orthopaedic patients.

Three groups of patients were clinically reviewed within a new orthopaedics department: patients who were on an inpatient waiting list for surgery; new referrals from general practitioners; and patients who had been referred earlier and were awaiting an appointment for outpatient consultation. Approximately two-fifths of patients who were already on the inpatient waiting list, and who had confirmed their wish to remain on it, were considered on clinical review not to require inpatient treatment. A third of patients attending for first outpatient consultations were immediately returned to the continuing care of their general practitioner and this proportion was higher (47%) amongst patients who were waiting for outpatient appointments and who had not been referred to a named hospital consultant. These findings draw attention to the possible inappropriate use of specialist hospital facilities because of clinical decisions taken by some general practitioners and also to variations in the threshold for surgical intervention used by hospital consultants. It is important that the medical profession develops a consensus approach to the clinical management of patients with common conditions. It is also important that clinical review of patients on inpatient waiting lists, especially those who have been waiting a long time, becomes a routine part of waiting list management. Under the new British health care system, it is likely that purchasers of health care will seek to ensure that these issues are being dealt with by hospitals with which they are considering placing contracts.     

MELD分级与Child分级对328例肝硬化患者临床评估的比较

目的比较MELD和Child分级评估差异,分析影响预后的危险因素。方法回顾328例肝硬化患者2.5年,计算入院当天MELD和Child分值,通过ROC曲线及截断值比较分析,利用Spearman等级相关检验研究两体系相关性。结果3个月生存期的患者两体系ROC曲线面积有显著差异(P<0.05),而生存期超过1年的患者MELD较Child分级无明显差异(P>0.05)。短期内MELD>13,敏感性为74.7%,特异性97.8%;胆红素>2.8 mg/dl,敏感性为53.7%,特异性93.5%;INR>1.53,敏感性为48.8%,特异性93.9%;有腹水,敏感性为67.1%,特异性58.9%。两体系显著相关(r=0.785,P<0.01)。结论MELD和Child均精确评估各生存期预后;MELD适宜评估急、危重患者,预后超过1年的患者无明显优势。MELD>13,胆红素>2.8 mg/dl,INR>1.53及有腹水均提示应尽快治疗以提高患者短期预后。     

Managing the Fife ENT (ear, nose and throat) waiting list: the 1989 review of problems.

In-patient activity of Fife Ear, Nose and Throat (ENT) wards and of Fife ENT consultants are higher than the Scottish averages. Out-patient activity appears to operate at a lower level and hundreds of patients remain on the Fife waiting list for operations. An analysis of 731 patients on the ENT waiting list in 1989 showed that 15% had been waiting for over three years. Over 350 hours of theatre time and over 3,200 in-patient bed days would be required to clear this waiting list. Adopting a guillotine tonsillectomy operative procedure without anaesthesia would make a major contribution to a rapid reduction of the waiting list. Although this is reported to be quick, relatively painless and remarkably free from haemorrhagic complications, it appears not to be acceptable in our medical culture at the moment. A life table analysis suggests that Fife is failing to operate on patients at a rate compatible with the needs of the community: current trends of operating suggest that over one half of patients will be on the waiting list for operations three years after being placed on it. The Secretary of State's 1989-90 waiting list initiative, the appointment of an extra ENT consultant and the allocation of additional operating theatre time may help to resolve these difficulties.     

终末期肝病模型联合血清钠评估肝硬化失代偿期患者的预后价值

目的 评价终末期肝病模型(MELD)联合血清钠模型(MELD-Na、MELDNa、MESO评分)在判断肝硬化失代偿期患者6、12个月预后方面的价值.方法 选择具有完整临床资料和随访结果的119例肝硬化患者进行回顾性分析,分别应用MELD、MELD-Na、MELDNa、MESO评分模型进行评分,并了解其6、12个月内的病死率,运用受试者工作特征(ROC)曲线下面积衡量各评分系统预测肝硬化失代偿期患者6、12个月预后的能力,并采用Z检验比较各系统的预测能力.结果 随访6、12个月中,生存和死亡患者间MELD、MELD-Na、MELDNa、MESO评分比较差异均有统计学意义.MELD-Na、MELDNa、MESO评分在判断患者6、12个月的预后方面其ROC曲线下面积均大于0.8,在数值上优于MELD评分,但差异无统计学意义.结论 MELD联合血清钠模型在判断肝硬化失代偿期患者6、12个月预后方面具有良好的准确性,但未显示比MELD评分有更佳的预测能力.     

The cardiac waiting game: are patients prioritized on the basis of clinical need?

Waiting lists for coronary artery bypass grafting (CABG) have been a recurring problem for many hospitals, putting pressure on hospitals to manage waiting lists more effectively. In this study, we audited the records of 1594 patients who had coronary artery bypass surgery in 1992 and 1993 in three London hospitals, to assess their waiting time experience. Patients' actual waiting times were compared with an appropriate waiting time defined using an adapted version of a Canadian urgency scoring system. Influence of other factors (sex, age, smoking, hypertension, diabetes and obesity) on actual waiting time was assessed. A comparison of patients' actual waiting times with an appropriate waiting time, defined by the urgency score, showed that only 38% were treated within the appropriate period. Thirty-four per cent were treated earlier than their ischaemic risk indicated, and 28% with high ischaemic risk were delayed. Actual waiting time was associated with a patient's sex and smoking status but not with the other factors studied. The current system of prioritizing patients awaiting CABG is not concordant with a measure of appropriate waiting time. This could have arisen due to a number of factors, including the contracting process, waiting list initiatives, and methods of waiting list administration and patient pressures. The use of a standard method for prioritizing patients would enable a more appropriate use of resources.     

Urgency coding as a dynamic tool in management of waiting lists for psychogeriatric nursing home care in The Netherlands

Criteria are used to prioritise patients on waiting lists for health care services. This is also true for waiting lists for admission to psychogeriatric nursing homes. A patient's position on these latter waiting lists is determined by (changes in) urgency and waiting time. The present article focuses on the process and outcome of an urgency coding system in a fair selection of patients. It discusses the use of urgency codes in the daily practice of waiting list management and the related waiting times. Patients and their informal caregivers were followed from entry on the waiting list to admission to a nursing home. Caregivers were interviewed during the waiting period and after their relative's admission to a nursing home, and the formal urgency codes on the waiting list were monitored. Seventy-eight of the initial 93 patients were admitted to a nursing home. High urgency codes were commonly assigned and the waiting times were shorter for patients with higher urgency codes. Negative consequences of an urgency coding system, e.g. patients with less urgency not being admitted at all and patients not being admitted to the nursing home of their choice, could not be demonstrated. Patients without higher urgency codes were admitted after a mean waiting time of 28 weeks. It may be questioned whether this long waiting time is problematic, because satisfaction of the caregivers with regard to waiting times was not influenced by the actual waiting times. An urgency coding system enables health care professionals to react to changes in the situation of both patients and caregivers by adjusting urgency codes to influence the length of time until nursing home admission.     

Nutritional aspects of liver transplantation

Most adult and pediatric liver transplantation candidates present several metabolic disturbances that lead to malnutrition. Because malnutrition may adversely affect morbidity and mortality of orthotopic liver transplantation, it is very important to carefully assess the nutritional status of the waiting list patients. Pretransplant nutritional therapy -- enteral or parenteral -- may positively influence liver metabolism, muscle function, and immune status. Nutrition therapy should continue in the short- and also in the long-term post-transplant periods. For malnourished patients, early post-transplant enteral or parenteral nutrition have been useful in improving nutritional status. Finally, the metabolic and nutritional care of the liver transplant donor must be considered to reduce allograft dysfunction indices.     

终末期肝病模型在临床中的研究进展

目前原发性肝癌的治疗仍以手术切除为首选。手术后有可能出现肝功能不全甚至肝功能衰竭导致患者死亡。因此,术前正确评估肝脏的储备功能,对选择合理的治疗方法,把握合适的肝切除范围,减少术后肝衰竭的发生率具有重要意义。鉴于CTP分级存在诸多不足,美国学者建立了新的评价体系——终末期肝病模型(MELD)评分系统。本研究就MELD在临床中研究进展做一综述。