Alessandro Nanni Costa

Current situation of donation after circulatory death in European countries

The aim of the present study was to describe the current situation of donation after circulatory death (DCD) in the Council of Europe, through a dedicated survey. Of 27 participating countries, only 10 confirmed any DCD activity, the highest one being described in Belgium, the Netherlands and the United Kingdom (mainly controlled) and France and Spain (mainly uncontrolled). During 2000–2009, as DCD increased, donation after brain death (DBD) decreased about 20% in the three countries with a predominant controlled DCD activity, while DBD had increased in the majority of European countries. The number of organs recovered and transplanted per DCD increased along time, although it remained substantially lower compared with DBD. During 2000–2008, 5004 organs were transplanted from DCD (4261 kidneys, 505 livers, 157 lungs and 81 pancreas). Short‐term outcomes of 2343 kidney recipients from controlled versus 649 from uncontrolled DCD were analyzed: primary non function occurred in 5% vs. 6.4% (P = NS) and delayed graft function in 50.2% vs. 75.7% (P < 0.001). In spite of this, 1 year graft survival was 85.9% vs. 88.9% (P = 0.04), respectively. DCD is increasingly accepted in Europe but still limited to a few countries. Controlled DCD might negatively impact DBD activity. The degree of utilization of DCD is lower compared with DBD. Short‐term results of DCD are promising with differences between kidney recipients transplanted from controlled versus uncontrolled DCD, an observation to be further analyzed.

The critical pathway for deceased donation: reportable uniformity in the approach to deceased donation

The critical pathway of deceased donation provides a systematic approach to the organ donation process, considering both donation after cardiac death than donation after brain death. The pathway provides a tool for assessing the potential of deceased donation and for the prospective identification and referral of possible deceased donors.

Liver Match, a prospective observational cohort study on liver transplantation in Italy: Study design and current practice of donor-recipient matching

BACKGROUND The Liver Match is an observational cohort study that prospectively enrolled liver transplantations performed at 20 out of 21 Italian Transplant Centres between June 2007 and May 2009. Aim of the study is to investigate the impact of donor/recipient matching on outcomes. In this report we describe the study methodology and provide a cross-sectional description of donor and recipient characteristics and of graft allocation. METHODS Adult primary transplants performed with deceased heart-beating donors were included. Relevant information on donors and recipients, organ procurement and allocation were prospectively entered in an ad hoc database within the National Transplant Centre web-based Network. Data were blindly analysed by an independent Biostatistical Board. RESULTS The study enrolled 1530 donor/recipient matches. Median donor age was 56 years. Female donors (n = 681, median 58, range 12-92 years) were older than males (n = 849, median 53, range 2-97 years, p < 0.0001). Donors older than 60 years were 42.2%, including 4.2% octogenarians. Brain death was due to non-traumatic causes in 1126 (73.6%) cases. Half of the donor population was overweight, 10.1% was obese and 7.6% diabetic. Hepatitis B core antibody (HBcAb) was present in 245 (16.0%) donors. The median Donor Risk Index (DRI) was 1.57 (>1.7 in 35.8%). The median cold ischaemia time was 7.3h (≥ 10 in 10.6%). Median age of recipients was 54 years, and 77.7% were males. Hepatocellular carcinoma (HCC) was the most frequent indication overall (44.4%), being a coindication in roughly 1/3 of cases, followed by viral cirrhosis without HCC (28.2%) and alcoholic cirrhosis without HCC (10.2%). Hepatitis C virus infection (with or without HCC) was the most frequent etiologic factor (45.9% of the whole population and 71.4% of viral-related cirrhosis), yet hepatitis B virus infection accounted for 28.6% of viral-related cirrhosis, and HBcAb positivity was found in 49.7% of recipients. The median Model for End Stage Liver Disease (MELD) at transplant was 12 in patients with HCC and 18 in those without. Multivariate analysis showed a slight but significant inverse association between DRI and MELD at transplant. CONCLUSIONS The deceased donor population in Italy has a high-risk profile compared to other countries, mainly due to older donor age. Almost half of the grafts are transplanted in recipients with HCC. Higher risk donors tend to be preferentially allocated to recipients with HCC, who are usually less ill and older. No other relevant allocation strategy is currently adopted at national level.

Liver transplantation from hepatitis B surface antigen positive donors: A safe way to expand the donor pool

BACKGROUND & AIMS The main limitation of orthotopic liver transplantation (OLT) is the scarcity of available donor organs. A possibility to increase the organ pool is to use grafts from hepatitis B virus surface antigen (HBsAg) positive donors, but few data are currently available in this setting. We assessed the clinical, serovirological, and immunological outcomes of liver transplant from HBsAg positive donors in a single centre study. METHODS From 2005 to 2009 10 patients underwent OLT from HBsAg positive donors, for HBV-related disease (n=6) or HBV-unrelated disease (n=4). The median follow-up was 42 months (range 12-60). All recipients were HBcAb positive and were given antiviral prophylaxis. RESULTS Patients transplanted for HBV-related disease never cleared HBsAg. Two HBsAg negative patients never tested positive for HBsAg, whereas the others experienced an HBsAg appearance, followed by spontaneous production of anti-HBs, allowing HBsAg clearance. No patient ever had any sign of HBV hepatitis. HBV replication was effectively controlled by antiviral therapy. The immunologic sub-study showed that a most robust anti-HBV specific T cell response was associated with the control of HBV infection. CONCLUSIONS OLT from HBsAg positive donors seems to be a safe procedure in the era of highly effective antiviral therapy.

Hepatitis B-core antibody positive donors in liver transplantation and their impact on graft survival: Evidence from the Liver Match cohort study

BACKGROUND & AIMS The appropriate allocation of grafts from HBcAb positive donors in liver transplantation is crucial, yet a consensus is still lacking. METHODS We evaluated this issue within Liver Match, a prospective observational Italian study. Data from 1437 consecutive, first transplants performed in 2007-2009 using grafts from deceased heart beating donors were analyzed (median follow-up: 1040 days). Of these, 219 (15.2%) were HBcAb positive. Sixty-six HBcAb positive grafts were allocated to HBsAg positive and 153 to HBsAg negative recipients. RESULTS 329 graft losses occurred (22.9%): 66 (30.1%) among 219 recipients of HBcAb positive grafts, and 263 (21.6%) among 1218 recipients of HBcAb negative grafts. Graft survival was lower in recipients of HBcAb positive compared to HBcAb negative donors, with unadjusted 3-year graft survival of 0.69 (s.e. 0.032) and 0.77 (0.013), respectively (log-rank, p=0.0047). After stratifying for recipient HBsAg status, this difference was only observed among HBsAg negative recipients (log rank, p=0.0007), 3-year graft survival being excellent (0.88, s.e. 0.020) among HBsAg positive recipients, regardless of the HBcAb donor status (log rank, p=0.4478). Graft loss due to de novo HBV hepatitis occurred only in one patient. At Cox regression, hazard ratios for graft loss were: MELD (1.30 per 10 units, p=0.0002), donor HBcAb positivity (1.56, p=0.0015), recipient HBsAg positivity (0.43, p <0.0001), portal vein thrombosis (1.99, p=0.0156), and DRI (1.41 per unit, p=0.0325). CONCLUSIONS HBcAb positive donor grafts have better outcomes when transplanted into HBsAg positive than HBsAg negative recipients. These findings suggest that donor HBcAb positivity requires more stringent allocation strategies.

Quality and Safety in the Italian Donor Evaluation Process

Background. The shortage of available organs, has increasingly prompted the use of elderly donors, with a consequent growth of possible risk factors. In this context the risk of donor-recipient transmission of infectious or neoplastic pathologies may be considered as a major issue; in each case for each organ potentially available, acceptable quality must be provided and unacceptable risks must be avoided. Methods. We are presenting here the process of risk management followed by the Italian centers. In 2001, the Italian National Transplant Centre created a national commission of experts, with the mission of defining guidelines for the evaluation process of the potential organ donor. As a supplement to these measures, the Italian National Transplant Centre has supported transplant network health workers through ad hoc developed information tools and an expert task force (second opinion) for evaluation of doubtful cases. Results. Starting from the date of guidelines application and second opinion start up, 9519 potential cadaveric donors were reported in Italy. Of these, 1611 presented a neoplastic or infectious risk. Over this period, 4861 donors were used for transplantation, equal to 48.5% of reported donors. Among the 1611 donors, who had been diagnosed at risk, 674 were neoplastic-disease affected donors and 937 infection-disease affected donors. Conclusions. At the European level, several new activities have been recently implemented to increase organ safety. In Italy, new guidelines and actions to ensure organ safety have been implemented. The evaluation of the impact of these actions will be performed in the near future.

Infections and organ transplantation: new challenges for prevention and treatment--a colloquium

Paolo A. Grossi, Alessandro Nanni Costa, Deirdre Fehily, Emily A. Blumberg, Matthew J. Kuehnert, Jay A. Fishman, Michael G. Ison, Roberta Lattes, Camille N. Kotton, Daniele Lilleri, Anne Kabanova, Antonio Lanzavecchia, Giuseppi Gerna, Raymund R. Razonable, Patrizia Comoli, Marco Zecca, Sabrina Basso, Fabrizio Ginevri, Alessandra Grossi, Francesco P. Schena, Antoni Rimola, Patrizia Burra, Elenora De Martin, Kryssia Isabel Rodriguez-Castro, Stefano Fagiuoli, Luisa Pasulo, Raffaele Bruno, Pietro Andreone, Elisabetta Loggi, Fabio Arena, Gian Maria Rossolini, Gabriele Sganga, and Valerio Cozza

Incidence of Carbapenem-Resistant Gram Negatives in Italian Transplant Recipients: A Nationwide Surveillance Study

Background Bacterial infections remain a challenge to solid organ transplantation. Due to the alarming spread of carbapenem-resistant gram negative bacteria, these organisms have been frequently recognized as cause of severe infections in solid organ transplant recipients. Methods and Findings Between 15 May and 30 September 2012 we enrolled 887 solid organ transplant recipients in Italy with the aim to describe the epidemiology of gram negative bacteria spreading, to explore potential risk factors and to assess the effect of early isolation of gram negative bacteria on recipients’ mortality during the first 90 days after transplantation. During the study period 185 clinical isolates of gram negative bacteria were reported, for an incidence of 2.39 per 1000 recipient-days. Positive cultures for gram negative bacteria occurred early after transplantation (median time 26 days; incidence rate 4.33, 1.67 and 1.14 per 1,000 recipient-days in the first, second and third month after SOT, respectively). Forty-nine of these clinical isolates were due to carbapenem-resistant gram negative bacteria (26.5%; incidence 0.63 per 1000 recipient-days). Carbapenems resistance was particularly frequent among Klebsiella spp. isolates (49.1%). Recipients with longer hospital stay and those who received either heart or lung graft were at the highest risk of testing positive for any gram negative bacteria. Moreover recipients with longer hospital stay, lung recipients and those admitted to hospital for more than 48h before transplantation had the highest probability to have culture(s) positive for carbapenem-resistant gram negative bacteria. Forty-four organ recipients died (0.57 per 1000 recipient-days) during the study period. Recipients with at least one positive culture for carbapenem-resistant gram negative bacteria had a 10.23-fold higher mortality rate than those who did not. Conclusion The isolation of gram-negative bacteria is most frequent among recipient with hospital stays >48 hours prior to transplant and in those receiving either heart or lung transplants. Carbapenem-resistant gram negative isolates are associated with significant mortality.

A colloquium on the congress "A gift for life. Considerations on organ donation".

Alessandro Nanni Costa, J. M. Simon i Castellvi, Antonio G. Spagnolo, Nunziata Comoretto, Jean Laffitte, Hakan Gabel, Francis L. Delmonico, Ferdinand Muehlbacher, Walter Schaupp, Alexandra K. Glazier, Valter D. Garcia, Mario Abbud-Filho, Jose O. Medina-Pestana, Mariangela Gritta Grainer, Pier Paolo Donadio, Anna Guermani, Riccardo Bosco, Francesco Giordano, Blanca Martinez Lopez de Arroyabe, Marco Brunetti, Marti Manyalich, Gloria Paez, Ricardo Valero, Rafael Matesanz, Elisabeth Coll, Beatriz Dominguez-Gil, Beatriz Mahillo, Eduardo Martin Escobar, Gregorio Garrido, and Felix Cantarovich

A population-based study of cancer incidence in solid organ transplants from donors at various risk of neoplasia

A population-based cohort study of recipients of organs from donors with a recognized history or active cancer has been conducted by linking the Italian National Registry of Transplanted Patients and the National Registry of Donors with Neoplasia Risk. Between 2002 and 2004, 8,198 solid organ transplants have been performed in Italy, 108 of them with organs from 59 cadaveric donors with various risk of neoplasia. There were two reported cases of nonmelanoma skin cancer during the follow up of the transplanted patients, which lasted 27.6±11.3 months (234 patient-years). In our study, recipients of organs from donors with various degree of neoplasia risk are exposed to a low risk of cancer transmission.