Cadaveric donor selection and management

The current availability of lung donors is far exceeded by the number of potential transplant recipients who are waiting for an organ. This disparity results in significant morbidity and mortality for those on the waiting list. Although it is desirable to increase overall consent rates for organ donation, doing so requires an intervention to affect societal response. In contrast, increased procurement of organs from marginal donors and improved donor management may be realized through increased study and practice changes within the transplant community. Transplantation of organs from marginal or extended-criteria donors may result in some increase in complications or mortality, but this possibility must be weighed against the morbidity and risk of death risk faced by individuals on the waiting list. The effects of this trade-off are currently being studied in kidney transplantation, and perhaps in the near future lung transplantation may benefit from a similar analysis. Until that time, the limited data regarding criteria for donor acceptability must be incorporated into practice to maximize the overall benefits of lung transplantation.     

Maximizing the donor pool: marginal donors, splits, and living donor liver transplants

Abstract   The shortage of donor organs is probably the biggest problem facing the field of liver transplantation today. Waiting lists have grown dramatically in the last 10 years. The consequences of this have been multiple, including higher waiting list mortality rates, longer waiting times, and more advanced liver disease in those patients coming to transplant. To address this issue, transplant centers are utilizing several techniques in an effort to expand the donor pool. These include the use of marginal donors (donors that would not have been considered suitable for donation previously), the use of living donors, and performing split liver transplants from deceased donors. The obvious advantage of these procedures is to expand the donor pool, hence increasing the number of transplants, and thus hopefully decreasing waiting list mortality rates. The disadvantage is that in many instances, such transplants may yield inferior results compared to standard transplants, or be associated with a higher incidence of complications. Further experience with such types of transplants will hopefully help to improve results and define the ideal manner in which to use these techniques to maximize the number of transplants.     

Current status of pediatric liver transplantation

Increased survival for young liver transplant recipients has greatly improved. Increasing success has led to broader indications, thereby increasing the number of potential recipients. Pediatric liver centers are developing new strategies to cope with the ever-increasing demands for suitable size appropriate grafts. UNOS is in the process of updating guidelines to regulate the sharing of organs which become available from new surgical techniques. In the future, alternative therapies, such as artificial liver assist devices and techniques of cellular transplantation and genetic modification of hepatocytes, may decrease the number of children who die while waiting for a suitable organ or even obviate the need for the liver transplantation.     

Living donor liver transplantation in adults

Adult-to-adult living donor liver transplantation (LDLT) using right hemi-liver has become a promising treatment modality for patients with end-stage liver disease. The rapid adoption of the procedure has been triggered mainly by the significant gap between available cadaver grafts and the number of patients on the waiting list for liver transplant. Since the arguments against LDLT focus only on the safety of the donor, the demonstration that the donor operation can be performed with minimal morbidity will make it more ethically acceptable. The advantages of LDLT are the possibility of performing an elective operation, access to a graft in best condition, and the possibility of lowering the likelihood of death while waiting for a suitable organ. As well as the standard indications for liver transplantation, LDLT opens up the possibility of treatment of patients with borderline indications. Further improvement of surgical and medical technology, careful long-term follow-up of donors and recipients, and profound analysis of socioeconomic aspects are essential issues for the transplantation community.     

Donation after cardio-circulatory death liver transplantation

The renewed interest in donation after cardio-circulatory death (DCD) started in the 1990s following the limited success of the transplant community to expand the donation after brain-death (DBD) organ supply and following the request of potential DCD families. Since then, DCD organ procurement and transplantation activities have rapidly expanded, particularly for non-vital organs, like kidneys. In liver transplantation (LT), DCD donors are a valuable organ source that helps to decrease the mortality rate on the waiting lists and to increase the availability of organs for transplantation despite a higher risk of early graft dysfunction, more frequent vascular and ischemia-type biliary lesions, higher rates of re-listing and re-transplantation and lower graft survival, which are obviously due to the inevitable warm ischemia occurring during the declaration of death and organ retrieval process. Experimental strategies intervening in both donors and recipients at different phases of the transplantation process have focused on the attenuation of ischemia-reperfusion injury and already gained encouraging results, and some of them have found their way from pre-clinical success into clinical reality. The future of DCD-LT is promising. Concerted efforts should concentrate on the identification of suitable donors (probably Maastricht category III DCD donors), better donor and recipient matching (high risk donors to low risk recipients), use of advanced organ preservation techniques (oxygenated hypothermic machine perfusion, normothermic machine perfusion, venous systemic oxygen persufflation), and pharmacological modulation (probably a multi-factorial biologic modulation strategy) so that DCD liver allografts could be safely utilized and attain equivalent results as DBD-LT.     

Kidney transplantation from donors with hepatitis C infection

The increasing demand for organ donors to supply the increasing number of patients on kidney waiting lists has led to most transplant centers developing protocols that allow safe utilization from donors with special clini cal situations which previously were regarded as contra indications.Deceased donors with previous hepatitis C infection may represent a safe resource to expand the donor pool.When allocated to serology-matched recipi ents,kidney transplantation from donors with hepatitis C may result in an excellent short-term outcome and a significant reduction of time on the waiting list.Specia care must be dedicated to the pre-transplant evaluation of potential candidates,particularly with regard to live functionality and evidence of liver histological damage such as cirrhosis,that could be a contraindication to transplantation.Pre-transplant antiviral therapy could be useful to reduce the viral load and to improve the long-term results,which may be affected by the progression of liver disease in the recipients.An accurate selection of both donor and recipient is mandatory to achieve a satisfactory long-term outcome.     

Successful heart‐kidney transplantation from a Hepatitis C viremic donor to negative recipient: One year of follow‐up

Every year the number of patients waiting for a heart transplant increases faster than the number of available donor organs. Some potential donor organs are from donors with active communicable diseases, including hepatitis C virus (HCV), potentially making donation prohibitive. The advent of direct‐acting antiviral agents for HCV has drastically changed the treatment of HCV. Recently, these agents have been used to treat HCV in organ donor recipients who acquired the disease from the donor organ. We report a case of heart‐kidney transplantation from an HCV viremic donor to HCV negative recipient with successful treatment and sustained virologic response.     

Leberlebendspende

Liver transplantation is the first-line therapy for irreversible acute liver failure, chronic end-stage liver disease, advanced metabolic liver disease, and hepatocellular carcinoma. The ongoing shortage of deceased donor organs and the waiting-list mortality have led to a change in allocation policy with the introduction of the model for end-stage liver disease. Living donation is a further option to reduce the waiting-list mortality. In pediatric recipients, living donation has almost eliminated death while on the waiting list, with excellent short-term and long-term outcomes after transplantation. In contrast, because adult recipients require a greater liver volume, a more extended liver resection is necessary, which increases the donor’s perioperative and postoperative morbidity and mortality risk. The donor’s safety is the greatest concern; therefore, meticulous evaluation and selection of the living donor is the basic prerequisite to reduce the donor risk. The postoperative outcome after living donor liver transplantation is comparable with that for full-size postmortal grafts. However, living donation has several advantages, including the elective setting of the transplantation, an excellent proven graft quality, and a short cold ischemia time. Living donor liver transplantation requires high expertise in liver surgery as well as in split-liver transplantation. Therefore, living donor liver transplantation should be performed only in transplant centers meeting these qualifications.     

Cardiac retransplantation: an ethical dilemma

PURPOSE OF REVIEW: The evolution of scientific advancements that paved the way for clinical cardiac transplantation spans the era of the 20 century, heart transplantation has revolutionized therapy for end-stage heart failure. Demand far exceeds supply, resulting in a long waiting period, and an increasing number of deaths while on a waiting list. The shortage of donors poses dilemmas for allocation of organs and managing the waiting list. RECENT FINDINGS: The disparity between the demand and supply for donor hearts makes cardiac retransplantation an ethical issue with some patients being allowed a second transplant while some patients are dying on the waiting list before receiving their first transplant, especially with overall sub-optimal outcomes compared with primary transplantation. SUMMARY: The cardiac transplant community is mandated to closely monitor the results of cardiac retransplantation to identify the appropriate candidate who should receive a retransplantation.     

Meldung von Patienten zur Transplantation

Kidney transplantation is in most cases the first choice for renal replacement procedures for advanced chronic and end-stage renal failure and is clearly superior to chronic dialysis treatment with respect to long-term survival. As far back as 1999 Wolfe et al. reported that the long-term mortality (>18?months) of recipients of a kidney transplant from deceased donors was reduced by 68% compared to dialysis patients remaining on the waiting list for a kidney transplant. In the immediate postoperative period the mortality of transplantation patients initially increases compared to waiting list patients but as early as 244?days after transplantation this effect turns to the opposite so that the cumulative mortality after transplantation is lower than for dialysis patients. The best form of transplantation is a preemptive (living) transplantation because this is coupled with the best survival of both transplants and patients. This is independent of age, underlying disease and ethnicity etc. On the basis of these results and due to a general increase in dialysis patients in recent years the number of waiting list patients for kidney transplants continuously rose before a plateau was reached in the last 2?years. Even if individual studies could repeatedly show an advantage of kidney transplantation, the individual factors associated with a large or small advantage for transplantation have so far been insufficiently described. Furthermore, there are currently few data on how the relative advantage of transplantation compared to dialysis changes in the course of time. This is even more important with respect to the fact that dialysis patients are becoming older and have more comorbidities and the simultaneous increase in waiting time for kidney transplantation due to the lack of organs.     

Analysis of hepatitis C virus-positive organs in liver transplantation.

The authors of this study note that in liver transplantation (LT), the survival rates of hepatitis C virus (HCV)-positive donors and HCV-negative receivers are comparable to those of HCV-negative donors and recipients. Direct-acting antiviral (DAA) therapies have nearly 100% effectiveness in treating HCV. Between 2006 and 2016, the percentages of HCV-positive patients on the waiting list and HCV-positive LT recipients fell by 8.2 percent and 7.6 percent, respectively. Records from April 1, 2014, in which the donor and receiver were both at least 18 years old and had a positive HCV status, were the only ones eligible for the study. The analysis for this study was restricted to the first transplant recorded for each patient using a data element that documented the number of prior transplants for each recipient, although some recipients appeared multiple times in the data set. HCV-positive recipients or people with fulminant hepatic failure were the main beneficiaries of primary biliary cirrhosis among HCV-positive donors. However, there is still a reticence to use HCV-positive donor organs in HCV recipients due to clinical and ethical considerations. Similar survival rates between HCV-positive donors and recipients and HCV-negative donors and receivers illustrate the efficacy of these DAA regimens.     

The Evolution of Living Kidney Donation and Transplantation in Older Adults

Kidney transplantation is a good option for adults aged 65 and older with end‐stage renal disease because it has been shown to reduce morbidity and mortality, improve quality of life, and is more cost‐effective than other renal replacement options. However, older age has been a deterrent to access to the deceased donor waiting list, and individuals aged 65 and older have a lower probability of being referred to and listed for transplantation compared to younger adults. Because the deceased organ supply is limited, living donor kidney transplantation offers an effective alternative for older adults facing long waiting times for cadaveric organs. This article describes the evolution of living kidney donation and transplantation in older adults over 15 years using the Organ Procurement and Transplantation Network/Scientific Registry of Transplant Recipients database. Between 1997 and 2011, 28,034 kidney transplantations were performed in adults aged 65 and older. Living‐donor and cadaveric kidney transplantation increased in older adults over the 15‐year period. Offspring are the most common living donors in this age group, followed by unrelated donors (e.g., friends), whereas the most common donors in younger transplant recipients are spouses, siblings, and parents. The number of living kidney donors aged 65 and older is slowly increasing, although the total number of transplants in this age group remains low. The expansion of living‐donor kidney transplantation in the aging population may offer a solution for organ shortage and thereby improve the quality of life of older adults. More research is needed to understand the older donor–recipient relationship and barriers to transplantation in this population.     

Ethical issues in transplantation: living related donation in the setting of severe neurological damage without brain death

The waiting list for renal transplantation has grown at an alarming rate over the last 2 decades, resulting in increased waiting times and deaths on the waiting list. To increase the number of available organs for transplantation, aggressive public education programs have been developed. The federal government has strengthened hospital regulations ensuring referral of all potential donors to organ recovery agencies, and living donor programs no longer limit donation to genetically related donors and recipients. We present a case that illustrates the complex ethical issues that are integral to the field of transplantation and the allocation of a scarce resource: a 50-year-old man who has a daughter with end-stage renal disease has suffered a severe cerebral vascular accident but is neither brain-dead nor a candidate for "non-heart-beating" donation. Given his poor prognosis, should the father be able to donate his kidney to the daughter in his compromised condition?     

Hot topics in liver transplantation: organ allocation--extended criteria donor--living donor liver transplantation

Liver transplantation has become the mainstay for the treatment of end-stage liver disease, hepatocellular cancer and some metabolic disorders. Its main drawback, though, is the disparity between the number of donors and the patients needing a liver graft. In this review we will discuss the recent changes regarding organ allocation, extended donor criteria, living donor liver transplantation and potential room for improvement. The gap between the number of donors and patients needing a liver graft forced the transplant community to introduce an objective model such as the modified model for end-stage liver disease (MELD) in order to obtain a transparent and fair organ allocation system. The use of extended criteria donor livers such as organs from older donors or steatotic grafts is one possibility to reduce the gap between patients on the waiting list and available donors. Finally, living donor liver transplantation has become a standard procedure in specialized centers as another possibility to reduce the donor shortage. Recent data clearly indicate that center experience is of major importance in achieving good results. Great progress has been made in recent years. However, further research is needed to improve results in the future.     

Should antihepatitis B virus core positive or antihepatitis C virus core positive subjects be accepted as organ donors for liver transplantation?

Since the introduction of liver transplantation as a routine surgical procedure for the treatment of end-stage liver disease, there has been an increasing gap between the number of available grafts and the number of patients on the waiting list. This has led transplant centers to expand the donor pool by different means. One of them has been the introduction of living donor liver transplantation. Other strategies include using less than optimal allografts from deceased donors, the so-called marginal donors, which include the use of grafts from older subjects, livers with moderate amounts of steatosis, or from donors with markers of past or current infection with hepatitis viruses who have absent or minimal liver biochemical or histologic injury. In this review, we will focus on the current use of allografts from donors with antihepatitis B core antibody and/or antibodies against hepatitis C virus in cadaveric and living donor liver transplantation.     

Lebertransplantation

After around 64 000 transplantations in Europe since 1988 liver transplantation has emerged as a standard treatment option for otherwise incurable chronic liver diseases. Cirrhosis of different etiologies represents the most frequent transplant indication. Overall survival in this group amounts to 72% after 5 years, and 62% after 10 years. In Germany, the main indications include alcoholic liver cirrhosis, tumors with increasing numbers in recent years, as well as viral diseases leading to cirrhosis. Since December 2006 the priority for liver transplantation is determined by the model for end stage liver disease (MELD) and not by the length of waiting time. MELD is a statistical model based on serum creatinine, serum bilirubin and coagulation, which describes the probability of 3-month mortality of a potential transplant candidate. Not all liver diseases are adequately represented by MELD necessitating the additional use of a defined number of standard exceptions that have been last updated in 2008. As a consequence of these developments indications, selection of recipients and the management of the waiting list have seen profound change.     

A review of public policies to procure and distribute kidneys for transplantation

The purpose of this article is to provide an up-to-date review of the current status of frequently changing public policies for the procurement and distribution of donor kidneys for transplantation. Issues in procurement involve the Uniform Anatomical Gift Act, criteria for brain death, routine inquiry/required request policies, and the use of living kidney donors. Issues in distribution involve access to the transplant waiting list and use of the new national point system to select recipients from the list. These public policies are relevant for internists, who often care for potential organ donors and patients with end-stage renal disease. The issues are also relevant for policy-minded physicians because renal transplantation is the paradigm for organ transplant policy.     

Expanding the donor pool: Hepatitis C,hepatitis B and human immunodeficiency virus-positive donors in liver transplantation

Liver transplantation (LT) remains the best option for patients with end-stage liver disease but the demand for organs from deceased donors continues to outweigh the available supply. The advent of highly effective anti-viral treatments has reduced the number of patients undergoing LT for hepatitis C (HCV) and hepatitis B (HBV) related liver disease and yet the number of patients waiting for LT continues to increase, driven by an increase in the patients listed with a diagnosis of cirrhosis due to non-alcoholic steatohepatitis and alcohol-related liver disease. In addition, human immunodeficiency virus (HIV) infection, which was previously a contra-indication for LT, is no longer a fatal disease due to the effectiveness of HIV therapy and patients with HIV and liver disease are now developing indications for LT. The rising demand for LT is projected to increase further in the future, thus driving the need to investigate potential means of expanding the pool of potential donors. One mechanism for doing so is utilizing organs from donors that previously would have been discarded or used only in exceptional circumstances such as HCV-positive, HBV-positive, and HIV-positive donors. The advent of highly effective anti-viral therapy has meant that these organs can now be used with excellent outcomes in HCV, HBV or HIV infected recipients and in some cases uninfected recipients.     

Special considerations for patients with cystic fibrosis undergoing lung transplantation

This article reviews lung transplantation in patients with cystic fibrosis (CF). Lung transplantation is commonly utilized for patients with end-stage CF. There are several characteristics of CF that present unique challenges before and after lung transplantation. There is new information available that can be utilized to predict outcomes in patients with end-stage CF, and therefore can help in decisions of referral and listing for lung transplantation. The new lung allocation score, which allocates organs to patients who are on the lung transplant waiting list in the United States, presents new challenges and opportunities for patients with end-stage CF. In addition, the effect of the presence of microbiological flora prior to lung transplantation has been better linked to outcomes after lung transplantation. It is now known that, other than those patients harboring Burkholderia cepacia in their lungs before transplantation, most CF patients can undergo transplantation successfully. Nutrition remains an important issue among CF patients, and diabetes is a common problem after lung transplantation. In contrast, liver disease does not usually present major problems but, if it is severe, can necessitate liver and lung transplantation. Mechanical ventilation prior to transplantation might not be an absolute contraindication for CF patients. CF lung transplant recipients have good outcomes after lung transplantation compared with those of other lung transplant recipients. Quality of life is dramatically improved. However, they are still prone to common complications that all lung transplant recipients are prone to, including primary graft dysfunction, acute and chronic rejection, a variety of infections and malignancies, and renal failure.     

Liver transplantation: Issues for the next 20 years

The growing numbers of potential transplant recipients on waiting lists is increasingly disproportionate to the supply of cadaveric donor organs. The hope for the next 20 years is that supply will satisfy demand. This requires both a reduction in indications for the procedure and an increase in the transplants performed. A multi-pronged approach is needed to increase cadaveric organ donation, generating enthusiasm for donation among both the general public and hospital staff. Accurate assessment of marginal grafts with stringent criteria known to predict graft function will diminish wastage of organs. Methods of rehabilitating marginal grafts during extracorporeal perfusion will increase organ availability. Supply of non-heart beating donors can be greatly expanded and protocols developed with ethical consent to optimize their initial function despite warm ischemia. Splitting livers that fulfill selection criteria, thus providing for two recipients, should be universally applied with acceptable incentives to those units who do not directly benefit. A proportion of recipients, though not those transplanted for autoimmune disease, will be spared the side-effects of immunosuppression thanks to immune tolerance. Protocols for close monitoring of those patients for rejection during treatment withdrawal must be carefully observed. In addition to gene therapy, it is highly likely that hepatocyte transplantation will replace orthotopic grafting in patients without cirrhosis, especially for inherited metabolic diseases. It is much more difficult to envisage that heterologous stem cell transplantation or xenotransplantation will have clinical impact in the next 20 years, although research in those areas has obvious long-term potential.