451 Targeted prophylaxis: Efficacy in preventing invasive fungal infection in orthotopic liver transplantation

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AASLD ABSTRACTS

45O VALIDATION AND USE OF A NEW MODEL TO MAXIMISE THE UTILITY OF LIVER ALLOGRAFTS. Geoffrey H Haydon,

The Queen ~ lizabeth Hospital, Birmingham, UK; YUo Hiltunen, Raahe Institute of Computer~ ngineering and Buisiness, Raahe, Finland; Michael R Lucey, Vanessa Rein, Thomas Chin, University of Wisconsin-Madison, Madison, WI; Peter G Nighffngale, Bridget Gunson, Nick Murphy, James Neuberger, The Queen ~ lizabeth Hospital, Birmingham, UK Introduction: The ideal liver allocation system would allocate donated livers to patients who are most likely to die without a transplant, but who have the lowest predicted mortality once they have been transplanted. This mode of allocation assesses the condition of both the recipient and the donor at the time of transplantation. In this study we have constructed a self-organising map (SOM: this is a neural network or non-linear mode of decision analysis suitable for modelling complex multidimensional relationships) and then validated it by using the SOM to classify survival in an unrelated population. Patients and Methods: We have previously described a SOM consisting of 72 (50 recipient and 22 donor) factors (inputs) constructed from 827 (449 male; median age 52 years; median MELD score 16) consecutive primary liver transplants undertaken between 01/01/1993 and 31/07/2002 in The Queen Elizabeth Hospital, Birmingham, UK. Using a 3 neuron version of this SOM with three output functions (patient survival at 3 months; I year and 5 years) we used the SOM to classify the post-transplant survival of all primary graft recipients (n-200 patients) over a 5 year period from a North American centre (125 male; median age 48 years; median MELD score 16). The Birmingham (UK) patients were first classified by the SOM and then the probabilities of survival (pi) at 3 months, I year and 5 years calculated by dividing the number of surviving patients by the total number of patients in neuron i. Using this SOM, each of the Wisconsin (US) patients was classified to each of the neurons and the distribution of survival probabilities for each neuron compared between the two populations using the chi squared test. Results: There was no significant difference in the survival probabilities of patients in each neuron w h e n the Wisconsin population was compared with the Birmingham population. Thus, the Birmingham SOM was able to classify successfully the survival of the Wisconsin patient population at 3 months, 1 year and 5 years following transplantation by using the same donor and recipient factors (Table 1). Analysis of the inter-neuronal survival probabilities demonstrated that for 3 m o n t h and I year survival, neuron 3 was associated with a significantly lower survival probability than neurons I and 2 (p-0.006 for 3 months; p - 0.006 for 12 months). Further, if recipients from neuron 1 received livers from patients classified to neuron 3 by "computer simulated transplantation", a proportion of patients then had a lower predicted survival probability (by SOM re-distribution to neuron 3). This analysis indicates that patient survival post-transplantation is significantly infuenced by both the condition of the recipient and donor factors at the time of transplantation. Conclusions: (1)SOM analysis provides an efficient and automated method for assessing the probability of survival of individual patients in an unrelated population at 3 months, 1 year and 5 years following liver transplantation. (2)The model not only assesses the pre-transplant condition of the patient, but also considers a wide range of donor factors w h e n predicting the probability of survival post-transplant. (3)This uniq ue resource can match a single liver to a population of recipients most likely to die without a transplant whilst ensuring the best possible post-transplant survival for the most suitable recipient (4)SOM analysis can also assess the probability of survival of individual recipents matched to a range of possible donated livers w h e n they are being considered for transplant programmes.

HEPATOLOGY, October 2003

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Disclosures: Thomas Chin - No relationships to disclose Bridget Gunson - No relationships to disclose Geoffrey H Haydon - No relationships to disclose Yrjo Hiltunen - No relationships to disclose Michael R Lucey - No relationships to disclose Nick Murphy - No relationships to disclose James Neuberger - No relationships to disclose Peter G Nightingale - No relationships to disclose Vanessa Rein - No relationships to disclose

451 TARGETED PROPHYLAXIS: EFFICACY IN PREVENTING INVASIVE FUNGAL INFECTION IN ORTHOTOPIC LIVER TRANSPLANTATION. Rebecca L Jones, Bristol Royal Infirmary,

Bristol, UK; Rhys W Vaughan, Antonia Marzec, Peter W Angus, Paul J Gow, Austin and Repatriation Medical Centre, Melbourne, Australia Purpose of study: To assess the efficacy of targeted prophylaxis in patients identified to be at highest risk of IFI after orthotopic liver transplantation. Introduction: Historically, invasive fungal infection (IH) has complicated up to 20% of cases of orthotopic liver transplantation (OLT). Retrospective analysis has identified a variety of risk factors associated with a high risk for the subsequent development of IFI. These indude patients undergoing retransplantation, transplantation for fulminant hepatic failure (FHF), requiring haemodialysis and prolonged intensive care unit (ICU) stay. Prophylactic anti-fungal therapy is safe and can reduce the incidence of IFI in OLT recipients. In recent years our unit has moved towards targeting prophylaxis to higher risk transplants. We assessed the efficacy of our policy in reducing the incidence of invasive fungal infection. Methods: A retrospective audit was conducted comparing two groups of adult OLT recipients over two 5 year time periods, 1990-1994 w h e n targeted prophylaxis was not used (Group 1) and 1997-2001 w h e n targeted prophylaxis was used (Group 2). Data were collected with respect to risk factors for IFI, anti-fungal prophylaxis use and development of IFI. Results: There was no difference in the overall number of risk factors for IFI associated with OLT between the two groups. However, a higher proportion of patients in Group 2 had high risk factors for IFI compared to Group 1 (p-0.07). There was a significant difference in the use of targeted anti-fungal prophylaxis given to high risk patients in Group 2 compared to Group 1 (52.3% cf 23.8%, p-0.03), and there was a significant reduction in the number of IFIs in Group2 compared with Group 1 (4.5% cf 28.6%, p-0.01). Conclusion: A policy of targeting anti-fungal prophylaxis to highest risk liver transplant recipients leads to a significant reduction in IFI this group. There remains a background incidence of infection in low risk or long term recipients in w h o m prophylaxis is not given. Disclosures: Peter W Angus - No relationships to disclose Paul J Gow - No relationships to disclose Rebecca L Jones - Gilead: Scientific Study/Trial; Other: RJ was sponsored by an educational grant administered through the ARMC medical research foundation. Antonia Marzec - No relationships to disclose Rhys W Vaughan - No relationships to disclose