A. Nanni Costa

A Multistep, Consensus‐Based Approach to Organ Allocation in Liver Transplantation: Toward a “Blended Principle Model”

Since Italian liver allocation policy was last revised (in 2012), relevant critical issues and conceptual advances have emerged, calling for significant improvements. We report the results of a national consensus conference process, promoted by the Italian College of Liver Transplant Surgeons (for the Italian Society for Organ Transplantation) and the Italian Association for the Study of the Liver, to review the best indicators for orienting organ allocation policies based on principles of urgency, utility, and transplant benefit in the light of current scientific evidence. MELD exceptions and hepatocellular carcinoma were analyzed to construct a transplantation priority algorithm, given the inequity of a purely MELD‐based system for governing organ allocation. Working groups of transplant surgeons and hepatologists prepared a list of statements for each topic, scoring their quality of evidence and strength of recommendation using the Centers for Disease Control grading system. A jury of Italian transplant surgeons, hepatologists, intensivists, infectious disease specialists, epidemiologists, representatives of patients’ associations and organ‐sharing organizations, transplant coordinators, and ethicists voted on and validated the proposed statements. After carefully reviewing the statements, a critical proposal for revising Italys current liver allocation policy was prepared jointly by transplant surgeons and hepatologists.

Successful Lung Transplantation in an HIV- and HBV-Positive Patient with Cystic Fibrosis

Prior to the advent of highly active antiretroviral therapy (HAART), HIV‐infected patients were usually not considered as transplant candidates because of the poor prognosis of their underlying disease and concerns regarding the potential detrimental effects of immunosuppression on viral load and immune status. However, with the significant HAART‐associated improvements in morbidity and mortality, good short‐term outcomes after liver and kidney transplantation for patients with HIV infection have been reported. Nevertheless, HIV infection is currently considered a contraindication to lung transplantation in most transplant centers worldwide. The results of a double lung transplant performed in an HIV and HBV co‐infected patient with cystic fibrosis (CF) and end‐stage respiratory failure (ESRF) are presented after a 2‐year follow‐up. Approval of and recommendations for the management of this patient were obtained from the Italian National Center for Transplantation as an extension of the ongoing Italian protocol for liver and kidney transplantation in HIV‐infected individuals. The operation was successful and the patient recovered rapidly after surgery. A cautious infectious and immunosuppressive management allowed so far the avoidance of major infectious complications and rejection. To the best of our knowledge, this is the first report of lung transplantation in an HIV and HBV co‐infected patient.

Report of Four Simultaneous Pancreas–Kidney Transplants in HIV-Positive Recipients With Favorable Outcomes

The advent of combined antiretroviral therapy (cART) dramatically changed the view of human immunodeficiency virus (HIV) infection as an exclusion criterion for solid organ transplantation, resulting in worldwide reports of successful transplants in HIV‐infected individuals. However, there are few reports on simultaneous pancreas–kidney transplant in HIV‐positive recipients detailing poor outcomes. A series of four pancreas–kidney transplant performed on HIV‐infected individuals between 2006 and 2009 is presented. All recipients reached stably undetectable HIV‐RNA after transplantation. All patients experienced early posttransplant infections (median day 30, range 9–128) with urinary tract infections and bacteremia being most commonly observed. In all cases, surgical complications led to laparotomic revisions (median day 18, range 1–44); two patients underwent cholecystectomy. One steroid‐responsive acute renal rejection (day 79) and one pancreatic graft failure (month 64) occurred. Frequent dose adjustments were required due to interference between cART and immunosuppressants. At a median follow‐up of 45 months (range, 26–67) we observed 100% patient survival with CD4 cell count >300 cells/mm3 for all patients. Although limited by its small number, this case series represents the largest reported to date with encouraging long‐term outcomes in HIV‐positive pancreas–kidney transplant recipients.

Italian Guidelines for Diagnosis, Prevention, and Treatment of Invasive Fungal Infections in Solid Organ Transplant Recipients

Use of various induction regimens, of novel immunosuppressive agents, and of newer prophylactic strategies continues to change the pattern of infections among solid organ transplant (SOT) recipients. Although invasive fungal infections (IFIs) occur at a lower incidence than bacterial and viral infections in this population, they remain a major cause of morbidity and mortality worldwide. In March 2008, a panel of Italian experts on fungal infections and organ transplantation convened in Castel Gandolfo (Rome) to develop consensus guidelines for the diagnosis, prevention, and treatment of IFIs among SOT recipients. We discussed the definitions, microbiological and radiological diagnoses, prophylaxis, empirical treatment, and therapy of established disease. Throughout the consensus document, recommendations as clinical guidelines were rated according to the standard scoring system of the Infectious Diseases Society of America and the United Stated Public Health Service.

EULID Project: European Living Donation and Public Health

The choice of transplantation from a living donor offers advantages over a deceased donor. However, it also carries disadvantages related to donor risks in terms of health and safety. Furthermore, there are several controversial ethical aspects to be taken into account. Several national and international institutions and the scientific community have stated standards that have great influence on professional codes and legislations. Living organ donation and transplantation are to some extent regulated by parliamentary acts in most European countries. It is necessary to take a step forward to develop a legal framework to regulate all of these processes to guarantee the quality and to prevent illegal and nonethical practices. It is also necessary to develop and implement living donor protection practices not only in terms of physical health, but also to minimize potential impacts on the psychological, social, and economic spheres. Finally, an additional effort should be made to create a database model with recommendations for registration practices as part of the standardized follow-up care for the living donor. The European Living Donation (EULID) projects (http://www.eulivingdonor.eu/) main objective was to contribute to a European consensus to set standards and recommendations about legal, ethical, and living donor protection practices to guarantee the health and safety of living donors.

Solid organ transplantation: the Italian experience in the international context.

The Italian experience in the organization of transplantation procedures could represent a relevant example of an internal development at a national level, combined with a strengthening of international collaborations. These results can be attributed first to the creation of the Italian National Transplant Centre (Centro Nazionale Trapianti [CNT]), and then to an ongoing European process that is leading to a greater awareness of the importance of closer collaboration between the organizations already existing and operating in the field of transplantation. This article summarizes the role and the most significant achievements of the CNT.

Emergency heart transplantation outcome: the Italian experience.

The National Program for Emergency Heart Transplantation (NP) was implemented in 2005 is managed at the national level by the Italian National Transplant Center. Patients admitted to the NP must be undergoing one of the following treatments: short-term Ventricular Assist Device (VAD); complicated medium or long-term VAD; complicated Total Artificial Heart; or mechanical ventilation associated with an Intra-Aortic Balloon Pump and Continuous Inotrope Therapy (intravenously). The aim of this study was to evaluate the NP experience from January 1, 2008, to December 31, 2009. We analyzed the number of requests (both fulfilled and not fulfilled), the timeliness of organ availability as well as graft and recipient survivals at 1 year. During the study period, 108 patients were admitted to the NP. The most frequent causes of admission were dilated cardiomyopathies (42.7%) and congenital cardiomyopathies (28.7%). Overall, whereas 12 subjects improved 65 patients underwent heart transplantation (60.2%) and 43 did not undergo surgery (39.8%) because of 31 succumbing before a heart became available. The median waiting time for heart transplantation was 3 days (range = 0.1-22), compared with median waiting time for elective heart transplantation (EHT) of 2.47 years. Graft and recipient survivals were 76.0 ± 1.06 compared with superior graft and recipient survivals for EHT during the same period (87.1 ± 2.0). However, implementation of NP has guaranteed heart availability at a short median time, thus allowing equitable management of this procedure.

Role of simian virus 40 in cancer incidence in solid organ transplant patients.

Transplant recipients have an increased risk of developing cancer in comparison with the general population. We present here data on cancer development in transplanted subjects who received organs from donors whose DNA was previously examined for the genomic insertion of Simian Virus 40 (SV40). Active follow-up of 387 recipients of solid organs donated by 134 donors, not clinically affected by cancer, was performed through the National Transplant Center (NTC). The average length of follow-up after transplant was 671±219 days (range 0–1085 days). Out of 134 proposed donors, 120 were utilised for organ donation. Of these, 12 (10%) were classified as positive for SV40 genomic insertion. None of the 41 recipients of organs from SV40 positive donors developed a tumour during the follow-up. In all, 11 recipients of organs given by SV40 negative donors developed a tumour (cancer incidence: 0.015 per year). In conclusion, cancer rates observed in our study are comparable to what reported by the literature in transplanted patients. Recipients of solid organs from SV40 positive donors do not have an increased risk of cancer after transplant. The role of SV40 in carcinogenesis in transplanted patients may be minimal.

Urgent Liver, Heart, and Lung Transplantation Programs in Italy: Activities and Evaluation of Outcomes

The Italian national transplantation network has set up programs for liver, heart, and lung transplantation in urgent conditions. The aim of this study was to analyze the capability of these programs to meeting needs and their quality. In period between 2008 and 2011, the total number of urgent transplant requests was analyzed by organ, reason, and outcome, namely waiting time, graft origin, and number of transplantations with their one- and three-year graft survivals. There were urgent requests for 312 livers, 268 hearts, and 43 lungs totted among which 72%, 63%, and 79% were met, respectively. Actuarial graft survival rates at one and three years were 62% and 61% for liver and 73.1% and 70.5% for heart transplantations, respectively. The rate of satisfied requests and the graft outcomes showed that the national urgency programs meet the healthcare needs of patients with a short life expectancy, achieving good quality donor-recipient match.

Ensuring Safety and Quality of Tissues in Italy: Application of European Directives

Three European Directives published in 2004 and 2006 require Member States to take a series of regulatory actions to ensure appropriate quality and safety of tissues and cells. These directives define responsibilities to inspect and certify centers, to put vigilance systems in place and to publish information on certified centers and their activities. A European-funded project led by the Italian National Transplant Centre has supported Member States in the development of common guidelines for inspection, tools for vigilance, and training for inspectors. In Italy, inspections are conducted every 2 years at each tissue bank, and a vigilance system has been launched. Information on Italian centers and their activity is published in the Eurocet Registry.