Background: Whether the use of rifaximin for hepatic encephalopathy during liver transplant candidacy has an impact on post-transplant infections is not known.Methods: We compared the frequency and spectrum of infections within 90 d post-transplant in liver transplant recipients who did and did not receive rifaximin for hepatic encephalopathy during transplant candidacy.Results: Of 110 consecutive liver transplant recipients, 30 (27%) received rifaximin. Rifaximin users were more severely ill based on higher Model for End-Stage Liver Disease (MELD) score (p = 0.005). When controlled for MELD (stratified by MELD < 30, MELD >= 30), the risk of infections was significantly lower in rifaximin vs. no rifaximin recipients (OR = 0.269, 95% CI 0.078-0.0.934, p = 0.026). Rifaximin use was not associated with a higher risk of multidrug resistant bacterial infections (OR = 1.8, 95% CI 0.42-8.35, p = 0.40). The probability of post-transplant survival at 90 d did not differ for patients with or without rifaximin use (0.90 for both groups, p = 0.56).Conclusions: Rifaximin appeared to have a protective effect against early post-transplant infections in more severely ill liver transplant recipients. Rifaximin use did not select for multidrug resistant bacteria in these patients.

Rationale and Design: The accuracy of a prospective histopathologic diagnosis of rejection and recurrent hepatitis C (HCV) was determined in 48 HCV RNA-positive liver allograft recipients enrolled in an "immunosuppression minimization protocol" between July 29, 2001 and January 24, 2003. Prospective entry of all pertinent treatment, laboratory, and histopathology results into an electronic database enabled a retrospective analysis of the accuracy of histopathologic diagnoses and the pathophysiologic relationship between recurrent HCV and rejection. Results: Time to first onset of acute rejection (AR) (mean, 107 days; median, 83 days; range, 7–329 days) overlapped with the time to first onset of recurrent HCV (mean, 115 days; median, 123 days; range, 22–315 days), making distinction between the two difficult. AR and chronic rejection (CR) with and without co-existent HCV showed overlapping but significantly different liver injury test profiles. One major and two minor errors occurred (positive predictive values for AR = 91%; recurrent HCV = 100%); all involved an overdiagnosis of AR in the context of recurrent HCV. Retrospective analysis of the mistakes showed that major errors can be avoided altogether and the impact of unavoidable minor errors can be minimized by strict adherence to specific histopathologic criteria, close clinicopathologic correlation including examination of HCV RNA levels, and a conservative approach to the use of additional immunosuppression. In addition, histopathologic diagnoses of moderate and severe AR and CR were associated with relatively low HCV RNA levels, whereas relatively high HCV RNA levels were associated with a histopathologic diagnosis of hepatitis alone, particularly the cholestatic variant of HCV. Conclusions: Liver allograft biopsy interpretation can rapidly and accurately distinguish between recurrent HCV and AR/CR. In addition, the histopathologic observations suggest that the immune mechanism responsible for HCV clearance overlap with those leading to significant rejection.

P118 Aims: To assess clinical outcomes using livers from controlled NHBD in the era of organ shortage with report on survival and complications on the largest single center experience with up to 10 years of follow-up. Methods: 61 liver transplants performed in 60 patients from NHBD between 1994-2004. Donors ranged between 4-68 years old (mean 38±16), with arrest to cross-clamp time of 6±5 minutes. Organs were flushed with Viaspan (45) or HTK (16) solutions using aortic cannulation. During this period 32 livers were discarded for documented anatomic and histologic reasons. The age of the recipients ranged from 18-69 years (50±11). Since mid-2002, we accepted NHBD livers recovered by other programs. 18 livers were imported (three transcontinental) and 14 transplanted. Results: Cold ischemia time was 358-1056 (630±144) minutes. Primary Non-Function (PNF) occurred in 6 patients (10%). Four retransplanted and three survived, two other died of sepsis. Hepatic artery thrombosis (HAT) occurred in 6 (11%) patients; three retransplanted and one survived; two died without re-transplantation and one survived with reconstruction. Biliary strictures or leaks were seen in 11 (18%) patients which four were irreversible (two required retransplantation, one died before re-transplantation and one re-listed). Nine patients were re-transplantaed for HAT (3), PNF (4) or biliary complications (2). Livers from NHBD were used to re-transplant seven emergency patients and five survived. Overall mortality in the group was 13 patients with 1-, 5-, and 10-year patient and graft survival of 80%, 78%, 76%, and 69%, 67% and 67% respectively. Organs procured by other programs did not show any difference in function or complications. Conclusions: The rate of PNF and major biliary complications was significantly higher than organs from heartbeating donors, leading to lower early graft survival, although long-term survival was not different. Thus, controlled NHBD remain an acceptable source of organs in the era of organ shortage.

Liver transplantation is a well-established treatment for liver failure and for a selected group of patients with hepatic tumors. The growing teratoma syndrome refers to the phenomenon whereby germ cell tumors enlarge after chemotherapy despite complete eradication of malignant cells and normalization of serum tumor markers. We present the case of a young patient with rapidly growing teratomatous masses in his liver who was treated with liver transplantation from a live donor. We discuss his postoperative management, follow-up, and briefly review literature on the subject.

Background. The Banff schema is the internationally accepted standard for grading acute liver-allograft rejection, but it has not been prospectively tested.Methods. Complete Banff grading was prospectively applied to 2,038 liver-allograft biopsies from 901 adult tacrolimus-treated primary hepatic allograft recipients between August 1995 and September 2001. Histopathologic data was melded with demographic, clinical, and laboratory data into a database on an ongoing basis using locally developed software.Results. Acute rejection developed in 575 of 901 (64%) patients and the worst grade was mild in 422 of 575 (73%). At least one episode of moderate or severe acute rejection developed in 153 of 901 (17%) patients and most episodes, irrespective of severity, occurred within the first year after transplantation. Patients with moderate or severe acute rejection showed higher alanine aminotransferase (P=0.007) and aspartate aminotransferase (P=0.07) levels and were more likely to develop perivenular fibrosis on follow-up biopsies (P=0.001) and graft failure from acute or chronic rejection (P=0.004) than those with mild rejection. Regardless of severity, 80% of patients with acute rejection did not develop significant fibrosis in follow-up biopsies, and graft failure from acute or chronic rejection occurred in only 11 of 901 (1%) allografts.Conclusions. Most acute-rejection episodes are mild and do not lead to clinically significant architectural sequelae. When tested prospectively under real-life and -time conditions, the Banff schema can be used to identify those few patients who are potentially at risk for more significant problems. Creation, capture, and integration of non-free text, or "digital," pathology data can be used to prospectively conduct outcomes-based research in transplantation.

ObjectiveTo evaluate the incidence of posttransplant lymphoproliferative disease (PTLD) and the risk factors and the impact of this complication on survival outcomes in a large cohort of liver transplant recipients at a single institution.Summary Background DataLiver transplantation has been accepted as a therapeutic option for patients with end-stage liver disease since 1983, in large part due to the availability and reliance on the use of nonspecifically directed immunosuppression. However, as predicted and subsequently verified in 1968, an increased incidence of certain de novo malignancies has been observed, particularly with regards to lymphoid neoplasms. While many reports have confirmed and clarified the nature of PTLD, the literature is fraught with conflicting experience and outcomes with PTLD.MethodsFour thousand consecutive patients who underwent liver transplants between February 1981 and April 1998 were included in this analysis and were followed to November 2001 The effect of recipient age at the time of transplant, recipient gender, diagnosis, baseline immunosuppression, grading of PTLD, and association with Epstein-Barr virus were compared. The causes of death were also examined. Treatment for PTLD varied over the 20-year period, but all included massive reduction or elimination of baseline immunosuppression.ResultsThe 1-year patient survival for liver transplant patients with PTLD was 85%, while the overall patient survival for the entire cohort was 53%. The actuarial 20-year survival was estimated at 45%. The overall median time to PTLD presentation was 10 months, and children had an incidence of PTLD that was threefold higher than adults. Patient survival was better in children, in patients transplanted in the era of tacrolimus immunosuppression, in patients with polymorphic PTLD, and in those with limited disease. Interestingly, neither the presence or absence of Epstein-Barr virus nor the timing of PTLD presentation appeared to influence overall patient survival. Patients transplanted for alcohol-related liver disease had a similar incidence of PTLD but had a higher risk of mortality.ConclusionsWhile PTLD continues to pose problems in patients receiving liver transplants, improvements in patient survival have been observed over time. While it is too early to assess the impact of new advances in prophylaxis, diagnosis, and treatment, such approaches are based on an increased knowledge of the pathophysiology of PTLD.

Development of sepsis is a major contributor to poor outcomes after liver transplant. The neutrophil-lymphocyte ratio (NLR) is an easily calculable inflammatory biomarker. We aim to utilize NLR to diagnose and predict the onset of sepsis in patients undergoing living donor liver transplants (LDLT).Analysis of the perioperative course of 314 consecutive adult patients who underwent elective ABO compatible LDLT was done. Patients were divided into two cohorts; those who developed sepsis and a control group. Sepsis was defined by the combination of SIRS and clinical/radiological suspicion of infection. NLR was calculated by dividing the percentage of neutrophils by the percentage of lymphocytes in peripheral blood.ostoperatively, 127 out of 314 patients (40.5%) having at least one episode of sepsis were included in the septic cohort and were compared to the 187 (59.5%) patients in the control group. Demographic and baseline characteristics, including NLR (13.74 ± 0.99 vs. 12.65 ± 0.57, P = 0.294) were comparable preoperatively. The NLR of the septic cohort was significantly higher than the control cohort (15.01 ± 1.67 vs. 9.98 ± 0.63, P = 0.001) 3 days prior to sepsis and remained significantly higher till the day of sepsis. The area under the cover was maximum for NLR 1 day prior to the development of sepsis (r = 0.707) with a sensitivity, specificity, positive predictive value, and negative predictive value of 62.4%, 62.2%, 51.4%, and 72.0%, respectively, at a cutoff of 8.5.NLR is a useful tool in diagnosing and pre-empting development of sepsis in LDLT.

OBJECTIVE:To evaluate the long-term survival outcomes of a large cohort of liver transplant recipients and to identify static and changing factors that influenced these outcomes over time.SUMMARY BACKGROUND DATA:Liver transplantation has been accepted as a therapeutic option for patients with end-stage liver disease since 1983, with continual improvements in patient survival as a result of advances in immunosuppression and medical management, technical achievements, and improvements in procurement and preservation. Although many reports, including registry data, have delineated short-term factors that influence survival, few reports have examined factors that affect long-term survival after liver transplantation.METHODS:Four thousand consecutive patients who underwent liver transplantation between February 1981 and April 1998 were included in this analysis and were followed up to March 2000. The effect of donor and recipient age at the time of transplantation, recipient gender, diagnosis, and year of transplantation were compared. Rates of retransplantation, causes of retransplantation, and cause of death were also examined.RESULTS:The overall patient survival for the entire cohort was 59%; the actuarial 18-year survival was 48%. Patient survival was significantly better in children, in female recipients, and in patients who received transplants after 1990. The rates of retransplantation for acute or chronic rejection were significantly lower with tacrolimus-based immunosuppression. The risk of graft failure and death was relatively stable after the first year, with recurrence of disease, malignancies, and age-related complications being the major factors for loss.CONCLUSION:Significantly improved patient and graft survival has been observed over time, and graft loss from acute or chronic rejection has emerged as a rarity. Age-related and disease-related causes of graft loss represent the greatest threat to long-term survival.

957 Post transplant lyphoproliferative disorder (PTLD) is a known complication in immunocompromised patients. Aim of the present study is to examine the incidence of PTLD in children and adults following primary liver transplantation (LTx) under tacrolimus and examine its impact on patient survival. Material: from Aug. 1989 to Dec. 1992, 1000 patients underwent primary LTx under tacrolimus. All patients were followed until Nov. 98 (mean follow-up 91, range 71 to 111, months). There were 166 children (age ≤18yrs.) and 834 adults (age 18yr). Physical findings, radiological studies, operative reports, histopathological examination and outcome of patient and graft were evaluated. Results: Overall 38(3.8%) patients developed PTLD 25male and 13 female. There were 20(2.4%) adults (mean age 44.3+14.6 range 19.7 to 69.7 yr.; 15 male, 5 female) and 18 (10.8%) children (mean age 4.3 ± 4.9, range 0.2 to 16.5 years; 18 boys, 8 girls), developed PTLD. Mean interval to develop PTLD in adults was 25.8 ± 30.1 (range 1.6 to 103.1) months, and in children was 16.3 ± 15.3 (range 2 to 63) months after LTx. Kaplan-Meier patient survival of PTLD after diagnosis is shown in the figure. The primary sites of PTLD in adults and children are shown in the table. Currently 16 children (88.9%) are alive (mean 71±28 months after PTLD) and 65% of adults are alive (mean 48±41 months after PTLD)(Log rank p=0.07)FigureTableSummary: Children are at five time's higher risk than adults for developing PTLD. However, survival for children was better 89% compared to adults 65%; in most of the cases, PTLD is controlled by reduction in immunosuppression.

The majority of children who undergo liver transplantation now survive into adulthood and their requirement for life-long follow-up means that they will need to transition from paediatric to adult services. Poor transition is a risk factor for poor clinical and psychosocial outcomes and one of the barriers to effective transition is vulnerability to risk-taking behaviours, and specifically non-adherence. This chapter focuses on practical considerations for transitioning young people from paediatric to adult services, with a particular focus on the risk factors associated with non-adherence and examples of interventions for managing it.

Kidney transplant recipients suffering from gouty arthritis often have shorter courses of persistent hyperuricemia: 6-14 months compared with 10-20 years in the general population. However; the effect of the immunosuppressive drugs used in kidney transplantation on the clinical presentation of acute inflammatory gouty arthritis is unknown. We conducted a retrospective chart review of all admissions during the preceding 5 years to detect differences in the clinical presentation/course of gouty arthritis between kidney transplant recipients and the population at large. There was a total of 17 separate episodes of gouty arthritis in 11 kidney transplant recipients and 5 episodes in 4 non-transplant patients. Podagra, the site of classic gouty arthritis, was present in only 3 (18%) of 17 episodes of gouty arthritis in kidney transplant recipients. Gouty arthritis in kidney transplant recipients was sometimes (5/17, 30%) mistaken for cellulitis and treated with antibiotics until uric acid crystals were found by joint aspiration. Therapy for gouty arthritis differed. kidney transplant recipients were given increased steroids; only rarely were NSAIDs used. After a usual unsatisfactory response, subsequent successful therapy with colchicine was applied. All 5 non-transplant patients were effectively treated with NSAIDs. We conclude that kidney transplant recipients with acute gouty arthritis evince fever and leukocytosis, equivalent to the general population. Additionally gouty arthritis in kidney transplant recipients may masquerade as infectious cellulitis. In kidney transplant recipients with severe gouty arthtitis, increasing the dose of steroids may not terminate the attack.

The influence of delayed renal graft function on long-term allograft outcome remains uncertain. All 495 cyclosporine treated cadaver donor renal transplants within a single center were analyzed with respect to dialysis dependence in the early posttransplant period. When compared with immediate allograft function, dialysis dependence for more than one week posttransplant was associated with prolonged cold ischemia time (27 +/- 11 vs 32 +/- 12 hours), cytotoxic antibodies > 30% (14% vs 25%), black race (29% vs 41%), increased incidence of acute rejection in the first year posttransplant (31% vs 67%) and inferior 1-year (85% vs 52%) and 5-year (68% vs 33%) graft survival among primary transplants. No adverse effect however was noted on renal function in long-term survivors.