Steroid-free Liver Transplantation Using Rabbit Antithymocyte Globulin Induction in 500 Consecutive Patients.

BACKGROUND: We have previously documented the efficacy of a steroid-free immunosuppression protocol using rabbit antithymocyte globulin (RATG) induction in orthotopic liver transplantation (OLT) with tacrolimus minimization. The purpose of this report is to demonstrate the benefits of this protocol in a large cohort of patients. METHODS: We evaluated outcomes of 500 consecutive OLT recipients who received RATG induction and a single dose of solumedrol given before the first dose of RATG. Mycophenolate mofetil was initiated postoperatively with delayed initiation of tacrolimus. Sirolimus replaced tacrolimus if serum creatinine remained above 2.0 mg/dL by day 7. Patients were weaned to tacrolimus or sirolimus monotherapy at 3 months. Mean model for end-stage liver disease (MELD) at transplantation was 22 ± 6. RESULTS: Forty-four percent of patients had hepatitis C. Posttransplant creatinine was highest at 1 month (1.43 ± 0.95 mg/dL) and improved to 1.26 ± 0.60 mg/dL (P < 0.05) at 2.5 years. Glomerular filtration rate was lowest at 1 month (65.6 ± 30.0) and improved by 1 year (72.7 ± 28.2, P < 0.01). Tacrolimus was initiated at 4.79 ± 13.3 days with a level of 4.95 ± 2.45 ng/mL at 1 year. One-year patient and graft survival were 92.8% and 89.6%, respectively, with a 3-year patient survival of 82.9%. Rejection occurred in 114 (22.8%) patients, 33 (6.6%) patients requiring steroids. Univariate and multivariate Cox proportional hazard analyses were performed to evaluate the effects of donor and recipient characteristics on patient and graft survivals. Pretransplant creatinine was consistently a statistically significant predictor for patient and graft survival. CONCLUSION: This is the largest reported series of OLT recipients using a steroid-free protocol with RATG induction demonstrating excellent outcomes, low complication rates, and preservation of renal function.

Liver transplant using donors after cardiac death: a single-center approach providing outcomes comparable to donation after brain death.

OBJECTIVES: Organ donation after cardiac death remains an available resource to meet the demand for transplant. However, concern persists that outcomes associated with donation after cardiac death liver allografts are not equivalent to those obtained with organ donation after brain death. The aim of this matched case control study was to determine if outcomes of liver transplants with donation after cardiac death donors is equivalent to outcomes with donation after brain death donors by controlling for careful donor and recipient selection, surgical technique, and preservation solution. MATERIALS AND METHODS: A retrospective, matched case control study of adult liver transplant recipients at the University of Tennessee/Methodist University Hospital Transplant Institute, Memphis, Tennessee was performed. Thirty-eight donation after cardiac death recipients were matched 1:2, with 76 donation after brain death recipients by recipient age, recipient laboratory Model for End Stage Liver Disease score, and donor age to form the 2 groups. A comprehensive approach that controlled for careful donor and recipient matching, surgical technique, and preservation solution was used to minimize warm ischemia time, cold ischemia time, and ischemia-reperfusion injury. RESULTS: Patient and graft survival rates were similar in both groups at 1 and 3 years (P = .444 and P = .295). There was no statistically significant difference in primary nonfunction, vascular complications, or biliary complications. In particular, there was no statistically significant difference in ischemic-type diffuse intrahepatic strictures (P = .107). CONCLUSIONS: These findings provide further evidence that excellent patient and graft survival rates expected with liver transplants using organ donation after brain death donors can be achieved with organ donation after cardiac death donors without statistically higher rates of morbidity or mortality when a comprehensive approach that controls for careful donor and recipient matching, surgical technique, and preservation solution is used.

Costs and Outcomes of Privately-Insured Kidney Transplant Recipients by Body Mass Index.

BACKGROUND: Obesity presents an additional challenge to the procedure of and recovery from kidney transplantation. As the prevalence of transplant candidates with an elevated body mass index (BMI) grows, researchers need to examine and quantify the increased risks and additional costs associated with the full spectrum of body composition. STUDY DESIGN: A retrospective cohort study design was used. SETTING & PARTICIPANTS: Data from a private health insurance provider were linked with records from the Organ Procurement and Transplantation Network to examine costs and health outcomes following kidney transplantation. FACTOR: BMI was used to predict costs and outcomes. OUTCOMES: The primary outcome of interest was posttransplant cost defined as insurance charges. Secondary outcomes of interest included delayed graft function, graft failure, patient survival, and length of transplant hospitalization. MEASUREMENTS: Categories of BMI followed selected cutoffs from World Health Organization International Classifications. Charges from recipient dialysis center, health providers, and treatment centers following transplant were summed during transplant hospitalization as well as each of three years following transplantation. RESULTS: Rates of graft failure were significantly increased for underweight, overweight, obese, and morbidly obese recipients. Recipients with elevated BMI had a significantly longer length of transplant hospitalization and an increased rate of delayed graft function. LIMITATIONS: Our analysis was limited to the quality and availability of the data included in the registry. Though inexpensive and easy to calculate, BMI may not be the best measure of body composition. Finally, BMI measurement is cross-sectional at time of transplant thereby limiting the potential for fluctuation of BMI before and after transplantation. CONCLUSIONS: The study results highlight the exponential concern associated with non-normal BMI for kidney transplant recipients. Transplant centers and insurance companies should consider funding weight management programs for transplant candidates as a means of obtaining preferred BMI and reducing costs associated with follow-up care.

Outcomes of orthotopic liver transplantation for hepatic sarcoidosis: an analysis of the United Network for Organ Sharing/Organ Procurement and Transplantation Network data files for a comparative study with cholestatic liver diseases.

Hepatic sarcoidosis is a rare indication for liver transplantation. Using the United Network for Organ Sharing (UNOS)/Organ Procurement and Transplantation Network (OPTN) database, we evaluated patient and graft survival after orthotopic liver transplantation for sarcoidosis between October 1987 and December 2007. We assessed the potential prognostic value of multiple demographic and clinical variables, and we also compared these patients to a case-matched group of patients with primary sclerosing cholangitis (PSC) or primary biliary cirrhosis (PBC). The 1- and 5-year survival rates for the sarcoidosis group were 78% and 61%, respectively, and these rates were significantly worse than the rates for the PSC/PBC group (P = 0.001). Disease recurrence in the liver is a rare cause of graft loss or patient death. Three deaths occurred in the sarcoidosis group because of recurrent hepatic sarcoidosis, and 1 death was a result of cardiac sarcoidosis. A univariate analysis identified an increasing donor risk index as a significant negative factor for outcomes for the sarcoidosis group [hazard ratio (HR) = 2.06, confidence interval (CI) = 1.04-4.06, P = 0.037], but this finding was not found in a multivariate analysis, in which no independent predictors were found to have a significant impact. A case-matched univariate analysis demonstrated that sarcoidosis and morbid obesity were significant negative factors for outcomes, and in a multivariate analysis, sarcoidosis continued to predict worse outcomes (HR = 2.39, CI = 1.21-4.73, P = 0.012). In conclusion, an analysis of the UNOS/OPTN database indicates that the patient and allograft survival rates for hepatic sarcoidosis are satisfactory, but they are worse in comparison with the rates for other cholestatic liver diseases.

Cyclopamine attenuates acute warm ischemia reperfusion injury in cholestatic rat liver: hope for marginal livers.

Cholestasis is a significant risk factor for immediate hepatic failure due to ischemia reperfusion (I/R) injury in patients undergoing liver surgery or transplantation. We recently demonstrated that inhibition of Hedgehog (Hh) signaling with cyclopamine (CYA) before I/R prevents liver injury. In this study we hypothesized that Hh signaling may modulate I/R injury in cholestatic rat liver. Cholestasis was induced by bile duct ligation (BDL). Seven days after BDL, rats were exposed to either CYA or vehicle for 7 days daily before being subjected to 30 min of ischemia and 4 h of reperfusion. Expression of Hh ligands (Sonic Hedgehog, Patched-1 and Glioblastoma-1), assessment of liver injury, neutrophil infiltration, cytokines, lipid peroxidation, cell proliferation and apoptosis were determined. Significant upregulation of Hh ligands was seen in vehicle treated BDL rats. I/R injury superimposed on these animals resulted in markedly elevated serum alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin accompanied with increased neutrophil recruitment and lipid peroxidation. Preconditioning with CYA reduced the histological damage and serum liver injury markers. CYA also reduced neutrophil infiltration, proinflammatory cytokines such as TNF-α and IL-1ß expression of α-smooth muscle actin and type 1 collagen resulting in reduced fibrosis. Furthermore CYA treated animals showed reduced cholangiocyte proliferation, and apoptosis. Hepatoprotection by CYA was conferred by reduced activation of protein kinase B (Akt) and extracellular signal regulated kinase (ERK). Endogenous Hh signaling in cholestasis exacerbates inflammatory injury during liver I/R. Blockade of Hh pathway represents a clinically relevant novel approach to limit I/R injury in cholestatic marginal liver.

Liver donor's age and recipient's serum creatinine predict blood component use during liver transplantation.

BACKGROUND: Excessive use of blood components during liver transplantation should be avoided because it has been associated with poor outcomes and it may stress blood bank resources. STUDY DESIGN AND METHODS: To determine preoperative predictors of excessive transfusion requirements in patients undergoing liver transplantation, the clinical records of 126 consecutive adult patients undergoing primary liver transplantation were retrospectively reviewed. Outcome variables included number of red blood cells (RBCs), plasma, and plateletpheresis components intraoperatively transfused. Univariate analyses of the following predictor variables were performed: recipient age, sex, ethnicity, height/weight, Model for End Stage Liver Disease score, year of transplant, previous abdominal surgery, hepatoma, wait-list time, standard recipient laboratory values obtained immediately before transplantation, cold ischemia time, donor age, sex, and height/weight. Multivariate analysis using logistic regression was used to build a model that best predicted how many blood components should be available before transplant. RESULTS: Donor age of more than 50 years old (odds ratio [OR], 2.8 95% confidence interval [CI], 1.3-6.0), and recipient serum creatinine (SCr) level of more than 1.3 mg/dL (OR, 3.8 95% CI, 1.6-8.9) were the only variables found to be predictive of RBC use in multivariate analysis. This model accurately predicted the use of more than 10 units of RBCs 79% of cases. Having both adverse factors present resulted in using more than one box in 80% of cases as compared to 44% of cases where only one or no adverse factor was present (p = 0.002). Further analyses showed a direct correlation between the number of RBCs transfused and plasma (r = 0.93) and plateletpheresis components (r = 0.74) transfused. [Corrections added after online publication 22-Jul-2009: OR updated from 3.8 to 2.8; CI from 1.6-8.9 to 1.3-6.0; OR from 2.8-3.8.] CONCLUSION: Liver donor's age and recipient's SCr are important in preoperatively predicting blood use during liver transplantation.

Magnetic resonance imaging in pancreas transplantation.

Magnetic resonance imaging (MRI) plays an important role in the evaluation of pancreas transplantation. Standard MRI, magnetic resonance angiography, and MR cholangiopancreatography can demonstrate the changes of the anatomy after transplantation. Vascular complications are assessed by MR angiography. Magnetic resonance cholangiopancreatography reveals ductal changes resulting from acute and/or chronic rejection and determines leaks with the use of a secretin-stimulated MR cholangiopancreatography. Serial contrast-enhanced MRI may detect the diminished perfusion that is related to the graft rejection or vascular complications. In this paper, we reviewed types of pancreas transplantation procedures, complications that arise in a short and/or a long term after the transplantation, and their assessment by MRI.

Bariatric surgery among kidney transplant candidates and recipients: analysis of the United States renal data system and literature review.

BACKGROUND: Limited data exist on the safety and efficacy of bariatric surgery (BS) in patients with kidney failure. METHODS: We examined Medicare billing claims within USRDS registry data (1991-2004) to identify BS cases among renal allograft candidates and recipients. RESULTS: Of 188 BS cases, 72 were performed pre-listing, 29 on the waitlist, and 87 post-transplant. Roux-en-Y gastric bypass was the most common procedure. Thirty-day mortality after BS performed on the waitlist and post-transplant was 3.5%, and one transplant recipient lost their graft within 30 days after BS. BMI data were available for a subset and suggested median excess body weight loss of 31%-61%. Comparison to published clinical trials of BS in populations without kidney disease indicates comparable weight loss but higher post-BS mortality in the USRDS sample. CONCLUSIONS: Given the substantial contributions of obesity to excess morbidity and mortality, BS warrants prospective study as a strategy for improving outcomes before and after kidney transplantation.

Flow cytometry crossmatch before kidney transplantation in contemporary practice: target cell utilization, results patterns, and associated long-term graft survival.

The flow cytometry crossmatch (FXCM) is an increasingly common method for pre-transplant crossmatching. We examined FCXM use in a national sample of kidney transplants, characterizing target cell utilization, results patterns, and associated graft outcomes. We queried Organ Procurement and Transplant Network Registry to identify kidney transplants performed in 1995-2007 with prospective FCXM testing for IgG antibodies against T-cells, B-cells or undifferentiated lymphocytes. FCXM was categorized according to target utilization and target-specific results. We modeled associations of FCXM testing-results patterns with risk of five-year graft loss and with projected graft survival by multivariable survival analysis. Sixty-five percent of the deceased donor transplants were performed with negative T-cell and B-cell FCXM, 16% with negative T-cell/unmeasured B-cell FCXM, 9% with negative undifferentiated lymphocyte FCXM, and < 0.5% with negative B-cell/unmeasured T-cell FCXM. Test results for at least one target were positive in 7.6% of transplants, most commonly in the form of B-cell positive/T-cell negative. Allograft survival was most favorable when both T-cell and B-cell FCXM targets were included and yielded negative results. Notably, B-cell positive/T-cell negative FCXM predicted elevated graft loss risk, with approximately 16% and 32% relative risk increases for deceased and living donor grafts, respectively, compared to negative T-cell and B-cell FCXM. Negative FCXM results with undifferentiated targets alone also predicted inferior graft survival. These data support the importance of using differentiated B-cell and T-cell targets for FCXM. Transplants that proceeded with positive FCXM experienced decrements in long-term graft survival - the decision to accept such risk must be individualized.

Hepatic artery thrombosis after adult living donor liver transplantation: the effect of center volume.

BACKGROUND: To investigate whether center volume impacts the rate hepatic artery thrombosis (HAT) and patient survival after adult living donor liver transplantation (ALDLT). METHODS: Patients with HAT who were listed as Status 1 in the Organ Procurement Transplant Network database were included in the study. Recipients of ALDLT were compared to those who received a deceased donor liver transplant (DDLT). RESULTS: Recipients of ALDLT had a higher rate of HAT than recipients of DDLT. Centers that performed less than four adult ALDLT had a higher rate of HAT than other higher volume centers. "Novice" centers had a worse graft and patient survival than those with more experience in ALDLT. Recipients who had HAT experienced a worse patient survival than those who did not. CONCLUSIONS: Centers with higher volume have a lower rate of HAT and a better patient and graft survival in ALDLT. Clearer regulations and focus on overcoming the learning curve might be needed to increase the utilization of ALDLT.