Both sarcopenia and frailty determine suitability of patients for liver transplantation-A systematic review and meta-analysis of the literature.

Liver grafts are allocated based on both urgency and utility. Due to a tremendous shortage of suitable organs for liver transplantation (LT), a careful selection of suitable recipients is of utmost importance. While the sickest first principle for organ allocation based on MELD score goes along with poor utility, other parameters reflecting the general health condition like frailty and sarcopenia might be essential to detect suitable patients for the waiting list. Thus, this study was designed to evaluate both frailty and sarcopenia in LT. A systematic review of the literature on sarcopenia and frailty measurements in liver transplant recipients was performed. Thirteen of 238 studies were selected for full paper review. Six of the studies investigating the impact of frailty on waitlist mortality were subjected to a meta-analysis. Despite the different methodologies to assess sarcopenia, reports showed that sarcopenia was highly related to waitlist mortality with a sum of all that highly favored negative outcome in case of sarcopenia. The existing literature clearly underlines that frailty and sarcopenia are important to determine in LT candidates. One unique index for transplant candidates reflecting frailty should be developed and be used as a standard in all transplant centers to facilitate comparability.

Immunological risk assessment: The key to individualized immunosuppression after kidney transplantation.

The wide range of immunosuppressive therapies and protocols permits tailored planning of the initial regimen according to the immunological risk status of individual patients. Pre-transplant risk assessment can include many factors, but there is no clear consensus on which parameters to take into account, and their relative importance. In general younger patients are known to be at higher risk for acute rejection, compounded by higher rates of non-adherence in adolescents. Donor age and recipient gender do not appear to exert a meaningful effect on risk of rejection per se, but black recipient ethnicity remains a well-established risk factor even under modern immunosuppression regimens. Little difference in risk is now observed between deceased- and living-donor recipients. Immunological risk assessment has developed substantially in recent years. Cross-match testing with cytotoxic analysis has long been supplemented by flow cytometry, but development of solid-phase single-bead antigen testing of solubilized human leukocyte antigens (HLA) to detect donor-specific antibodies (DSA) permits a far more nuanced stratification of immunological risk status, including the different classes and intensities of HLA antibodies Class I and/or II, including HLA-DSA. Immunologic risk evaluation is now often based on a combination of these tests, but other assessments are becoming more widely introduced, such as measurement of non-HLA antibodies against angiotensin type 1 (AT1) receptors or T-cell ELISPOT assay of alloantigen-specific donor. Targeted densensitization protocols can improve immunological risk, notably for DSA-positive patients with negative cytotoxicity and flow cross-match. HLA mismatch remains an important and undisputed risk factor for rejection. Delayed graft function also increases the risk of subsequent acute rejection, and the early regimen can be modified in such cases. Overall, there is a shift towards planning the immunosuppressive regimen based on pre-transplant immunology testing although certain conventional risk factors retain their importance.

Outcomes Following ABO-Incompatible Kidney Transplantation Performed After Desensitization by Nonantigen-Specific Immunoadsorption.

BACKGROUND: For desensitization of ABO-incompatible kidney transplant recipients we recently proposed nonantigen-specific immunoadsorption (IA) and rituximab. METHODS: We now compared clinical outcomes of 34 ABO-incompatible living-donor kidney recipients who were transplanted using this protocol with that of 68 matched ABO-compatible patients. In addition, we analyzed efficacy and cost of nonantigen-specific as compared to blood group antigen-specific IA. RESULTS: Before desensitization, the median isoagglutinin titer of 34 ABO-incompatible patients was 1:64 (Coombs technique). Patients received a median of 7 preoperative IA treatments. Twenty-four patients had a median of 2 additional plasmapheresis treatments to reach the preoperative target isoagglutinin titer of 1:8 or less. After a median postoperative follow-up of 22 months, overall graft survival in the ABO-incompatible group was not significantly different from that in ABO-compatible patients (log-rank P = 0.20), whereas patient survival tended to be lower (log-rank P = 0.05). The incidence of rejection episodes was 15% in both groups. The ABO-incompatible kidney recipients had a higher incidence of BK virus replication (P = 0.04) and nephropathy (P = 0.01) and showed more often colonization with multidrug resistant bacteria (P = 0.02). In comparison to blood group antigen-specific IA, nonantigen-specific IA showed equal efficacy but was associated with reduction in cost. CONCLUSIONS: Clinical outcomes of ABO-incompatible patients desensitized with a nonantigen-specific IA device and rituximab do not differ from that of matched ABO-compatible patients although a trend toward reduced patient survival was noted. Special attention must be paid to the higher incidence of BK virus infection in recipients of ABO-incompatible grafts.

Expanding the indications of pancreas transplantation alone.

OBJECTIVES: Total pancreatectomy (TP) is associated with postoperative endocrine and exocrine insufficiency. Especially, insulin therapy reduces quality of life and may lead to long-term complications. We review the literature with regard to the potential option of pancreas transplantation alone (PTA) after TP in patients with chronic pancreatitis or benign tumors. METHODS: A MEDLINE search (1958-2013) using the terminologies pancreas transplantation, pancreas transplantation alone, total pancreatectomy, morbidity, mortality, insulin therapy, and quality of life was performed. In addition, the current book and congress publications were reviewed. RESULTS: Total pancreatectomy after benign and borderline tumors as well as chronic pancreatitis is continuously increasing. Despite improvement of exogenous insulin therapy, more than 50% of these patients experience severe glucose control problems, which cause up to 50% long-term mortality. Pancreas transplantation alone can cure both endocrine and exocrine insufficiency and reduce the associated risks. The 3-year graft and patient survival rates after PTA are up to 73% and 100%, respectively. CONCLUSIONS: Pancreas transplantation alone after TP in patients with pancreatitis or benign tumors improves the recipient's quality of life and reduces long-term mortality. Considering the amount of available organs and potential candidates, PTA can be a treatment option for patients after TP with chronic pancreatitis or benign tumors.

Prediction of postoperative mortality in liver transplantation in the era of MELD-based liver allocation: a multivariate analysis.

BACKGROUND AND AIMS: Liver transplantation is the only curative treatment for end-stage liver disease. While waiting list mortality can be predicted by the MELD-score, reliable scoring systems for the postoperative period do not exist. This study's objective was to identify risk factors that contribute to postoperative mortality. METHODS: Between December 2006 and March 2011, 429 patients underwent liver transplantation in our department. Risk factors for postoperative mortality in 266 consecutive liver transplantations were identified using univariate and multivariate analyses. Patients who were <18 years, HU-listings, and split-, living related, combined or re-transplantations were excluded from the analysis. The correlation between number of risk factors and mortality was analyzed. RESULTS: A labMELD ≥20, female sex, coronary heart disease, donor risk index >1.5 and donor Na+>145 mmol/L were identified to be independent predictive factors for postoperative mortality. With increasing number of these risk-factors, postoperative 90-day and 1-year mortality increased (0-1: 0 and 0%; 2: 2.9 and 17.4%; 3: 5.6 and 16.8%; 4: 22.2 and 33.3%; 5-6: 60.9 and 66.2%). CONCLUSIONS: In this analysis, a simple score was derived that adequately identified patients at risk after liver transplantation. Opening a discussion on the inclusion of these parameters in the process of organ allocation may be a worthwhile venture.

ABO-incompatible kidney transplantation enabled by non-antigen-specific immunoadsorption.

BACKGROUND: ABO-incompatible kidney transplantation performed after desensitization with antigen-specific immunoadsorption (IA) results in good outcomes. However, a unique single-use IA device is required, which creates high costs. METHODS: From August 2005 to August 2010, 19 patients were desensitized for ABO-incompatible living donor kidney transplantation. Six patients treated with a single-use antigen-specific IA device and 12 patients treated with a reusable non-antigen-specific IA device were analyzed. RESULTS: Six patients who received antigen-specific IA had a median of 5 IA treatments and 12 patients with non-antigen-specific IA had a median of 6 IA treatments preoperatively. Median average titer drop in Coombs technique was 1.2 in antigen-specific IA and 1.7 in non-antigen-specific IA. In two patients with antigen-specific IA and four patients with non-antigen-specific IA, additional plasmapheresis treatments were necessary for recipient desensitization. Despite six treatments with antigen-specific IA and 12 plasmapheresis treatments, one patient with a starting isoagglutinin titer of 1:1024 (Coombs) could not be transplanted. The 18-month graft survival rate for the 17 ABO-incompatible living donor kidney transplants was 100%. One male recipient who was desensitized with antigen-specific IA died 44 months after transplantation from sudden cardiac death with a serum creatinine of 1.2 mg/dL. At last follow-up, a median of 13 months after transplantation, median serum creatinine for 16 patients was 1.5 mg/dL, median glomerular filtration rate as estimated by the modification of diet in renal disease formula 54 mL/min/1.73 m, and median urinary protein-to-creatinine ratio 0.1, with no differences between treatments. CONCLUSIONS: A reusable non-antigen-specific IA device allows high number of treatments at reasonable cost, and at the same time might deplete human leukocyte antigen-alloantibodies.

LabMELD-based organ allocation increases total costs of liver transplantation: a single-center experience.

INTRODUCTION: In 2006, model for end-stage liver disease (MELD)-based allocation was implemented in the Eurotransplant (ET) region. Sick patients, who in general require more resources, are prioritized. In this analysis, the effect of MELD on costs for liver transplantation (LTx) was assessed. METHODS: Total costs for LTx before and after implementation of MELD were identified in 256 patients from January 2005-December 2007. Forty-nine patients (Re-LTx, HU listings, and 30-d mortality) were excluded from further analysis. The costs of LTx in 207 patients have been correlated with their corresponding labMELD; 84 and 123 LTx before and after implementation of MELD were compared, and patient survival was monitored. RESULTS: A positive correlation exists between labMELD and costs (r(2) = 0.28; p < 0.05). Only nominal correlation existed between the Child-Pugh classification and costs. The labMELD scores can be stratified into four groups (I: 6-10, II: 11-18, III: 19-24, and IV: >24), with an increase of €15.672 ± 2.233 between each group (p < 0.05). Recipients' labMELD at the time of LTx increased significantly in the MELD-based allocation system. Costs increased by €11.650/patient (p < 0.05), while median survival decreased from 1219 to 869 d (p < 0.05). CONCLUSION: LabMELD-based allocation increased total costs of LTx. In accordance with other studies, the sickest patients need the most resources.

Cost distribution of orthotopic liver transplantation: single-center analysis under DRG-based reimbursement.

Costs of orthotopic liver transplantation (OLT) are influenced by multiple factors. Surgeons must be interested in determining the probability of meeting the projected cost averages. Costs of procedures, labor, drugs and pharmaceuticals, materials, and overhead costs of infrastructure were calculated during the primary stay in 38 consecutive patients undergoing OLT at a single center. Endpoint of cost aggregation was discharge from acute care. Costs per patient were grouped to plot the cost density distribution function. Mean cost of OLT was 49,000. Costs showed a large variation, ranging from 18,000 to 189,000 per case. Most patients were grouped in the G-DRG-A01C split (n=31), which characterizes the least resource consumptive split. Costs of OLT were not normally distributed. There was a left-skewed beta-distribution of costs. Labor-related costs were responsible for the largest cost fraction (mean 42.9%), whereas drugs and medication accounted for 24.9% on average. Most patients could be transplanted within cost groups below 50,000. The marked cost heterogeneity after OLT suggests that primarily medical comorbidities are of relevance for extraordinary resource consumption. A minimum number of transplants should be performed in single institutions to improve chances to financially counterbalance higher costs of individual cases under DRG-based reimbursement. Small programs have to bear increased risks of financial distortion. The asymmetry of cost distribution after OLT should be taken into account in future reimbursement regulations.