Susan Lerner

Preoperative factors associated with outcome and their impact on resource use in 1148 consecutive primary liver transplants.

BACKGROUND Hepatic transplantation is a highly effective but costly treatment for end-stage hepatic dysfunction. One approach to improve efficiency in the use of scarce organs for transplantation is to identify preoperative factors that are associated with poor outcome posttransplantation. This may assist both in selecting patients optimal for transplantation and in identifying strategies to improve survival. METHODS In the present work, we retrospectively reviewed consecutive liver transplants performed at the University of California at Los Angeles during a 6-year period and determined preoperative variables that were associated with outcome in primary grafts. In addition, we used the hospitals cost accounting database to determine the impact of these variables on the degree of resource use by high-risk patients. RESULTS We found five variables to have independent prognostic value in predicting graft survival after primary liver transplantation: (1) donor age, (2) recipient age, (3) donor sodium, (4) recipient creatinine, and (5) recipient ventilator requirement pretransplant. Recipient ventilator requirement and elevated creatinine were associated with significant increases in resource use during the transplant admission. CONCLUSIONS Patients at high risk for graft failure and costly transplants can be identified preoperatively by a set of parameters that are readily available, noninvasive, and inexpensive. Selection of recipients on the basis of these data would improve the efficiency of liver transplantation and reduce its cost.

Predictors of Survival After In Vivo Split Liver Transplantation: Analysis of 110 Consecutive Patients

ObjectiveTo determine the factors that influence patient survival after in vivo split liver transplantation (SLT). Summary Background DataSplit liver transplantation is effective in expanding the donor pool, and its use reduces the number of deaths in patients awaiting orthotopic liver transplantation. Early SLTs were associated with poor outcomes, and acceptance of the technique has been slow. A better understanding of the factors that influence patient and graft survival would be useful in widening the application of SLT. MethodsDuring a 3.5-year period, 55 right and 55 left lateral in vivo split grafts were transplanted in 102 pediatric and adult recipients. The authors’ in vivo split technique has been previously described. Median follow-up was 14.5 months. Recipient, donor, and surgical variables were analyzed for their effect on patient survival after SLT. ResultsOverall survival rates of patients who received an SLT were not significantly different from those of patients who received whole organ transplants. Survival of left lateral segment recipients, at median follow-up time, was 76% versus 80% in patients receiving a trisegment. Fifty of 102 patients (49%) were high-risk urgent recipients (United Network for Organ Sharing [UNOS] status 1 and 2A) and 52 (51%) were nonurgent recipients (UNOS status 2B, 3). High-risk recipients had a survival rate significantly lower than that of nonurgent recipients. By univariate comparison, two variables—UNOS status and number of transplants per patient—were significantly associated with an increased risk of death. Preoperative recipient mechanical ventilation, preoperative prothrombin time, donor sodium level, donor length of hospital stay, and warm ischemia time approached significance. The type of graft (right vs. left) did not reduce the survival rate after transplantation. Multivariate logistic regression analysis identified UNOS status and length of donor hospital stay as independent predictors of survival. ConclusionsPatient survival of in vivo SLT is not significantly different from that of whole-organ orthotopic liver transplantation. The variables affecting outcome of in vivo SLT are similar to those in whole-organ transplantation. in vivo SLT should be widely applied to expand a severely depleted donor pool.

Comparison of activation requirements and activation phenotype of allogeneic and xenogeneic rodent responses in vivo and in vitro

Background. Both discordant and concordant xenogeneic responses are dominated by humoral immunity. Recent advances in molecular engineering approaches may largely prevent rejection by means of this pathway, leaving the cellular arm of the immune response as the principal remaining barrier to successful engraftment. Methods. To characterize further the cellular response to xenogeneic tissues, we used the intracellular fluorescent marker CFSE (5-(and-6)-carboxyfluorescein diacetate succinimidyl ester) to track the mitotic record of T cells (and T cell subsets) after either xenogeneic or allogeneic activation in vitro or in vivo. Activation marker expression was monitored by simultaneous labeling with antibodies for either CD25 or CD134. Results. The in vitro and in vivo responses of Lewis lymphocytes were generally similar in magnitude and timing comparing activation with allogeneic or xenogeneic stimulators. However, the xenogeneic T cell precursor frequency was found to be markedly higher than that previously reported and were comparable to that seen in allogeneic responses. Xenogeneic responses were unique in the continued expression of activation markers in later division cycles. In addition, CD4 and CD8 T-cell proliferation was highly dependent on stimulator class II expression, highlighting the importance of CD4 T cells and the indirect pathway in the xenogeneic response. Conclusions. An unexpectedly high precursor frequency was detected for xenogeneic cellular responses in the rat anti-mouse combination and was comparable to that seen in allogeneic responses. Differences in xenogeneic versus allogeneic activation profiles exist that may result from the cellular pathways used for activation.

Higher Rates of Rejection in HIV-infected Kidney Transplant Recipients on Ritonavir-Boosted Protease Inhibitors-Three-Year Follow Up

Background One-year rejection rates in HIV-infected kidney transplant recipients range from 15-40%, compared to overall rejection rates of 10% in HIV-negative patients. Protocols for immunosuppression and highly active antiretroviral therapy (HAART) vary substantially and there is potential for significant drug-drug interactions, specifically between ritonavir-boosted protease inhibitors (rtv+ PI) and calcineurin inhibitors. Methods This is an IRB-approved, single center, retrospective study of adult HIV-infected patients who underwent a kidney transplantation between 5/2009 to 12/2014 with a three-year follow up for each patient. Results Forty-two patients were identified with a median age of 52 (47, 57) years. Of these, 81% were male and 50% were African American, 29% were Hispanic, and 17% were Caucasian. The most common cause of renal failure was hypertensive nephrosclerosis (50%) followed by HIV-associated nephropathy (14%), and the median duration of pre-transplant dialysis was 5.8 (2.8, 8.7) years. All patients were induced with IL-2 receptor antagonist (IL-2 RA): 83% with basiliximab and 17% with daclizumab induction. Calcineurin inhibitor therapy included tacrolimus (76%), cyclosporine (17%), or transitions between these two (7%). 40% of patients received a rtv+ PI-based HAART regimen. At 30 days, patient and graft survival were 100%. Patient and graft survival were consistent at 93% and 90%, respectively, at years one, two, and three. Overall treated biopsy-proven rejection rates at one, two, and three years were 38%, 38%, and 41%, respectively, and 92% of these episodes were acute rejection. At one, two, and three years, rejection rates were significantly higher for recipients on rtv+PI compared to those on other HAART regimens as 59% vs 24% (p=0.029), 59% vs 24% (p=0.029), and 68% vs 24% (p=0.01), respectively. Conclusion HIV-infected kidney transplant recipients maintain excellent outcomes despite higher rates of acute rejection relative to HIV negative recipients. Given the significantly higher rates of rejection at one, two, and three years in the rtv + PI group, alternative HAART regimens should be considered prior to transplant when possible.