Q. Lai

Metabolic Syndrome and Cardiovascular Risk after Liver Transplantation: A Single-Center Experience

Excessive weight gain, hypertension, hyperlipidemia, and diabetes are frequently observed among orthotopic liver transplantation (OLT) patients. These alterations, which are probably multifactorial in origin, contribute to posttransplantation metabolic syndrome (PTMS), which increases the risk of cardiovascular events. We assessed the prevalence of PTMS (diagnosed according to modified NCEP Adult Treatment Panel III criteria) in 156 OLT patients undergoing regular follow-up after transplantation (median 68 months; range, 6 to 234 months). Several pre- and post-OLT data were collected to identify the factors associated with the presence of PTMS which was found in 28% of cases. The only independent predictive factors for PTMS were diabetes mellitus and patients who were overweight or obese before-OLT. The prevalence of PTSM was lower among patients on tacrolimus immunosuppression. In our population, 21% of patients showed a high cardiovascular risk score with a 4% incidence of cardiovascular events, which was higher among subjects with PTMS. Close follow-up is mandatory to prevent the development of PTMS mainly among overweight and diabetic patients before transplantation.

Predictive Parameters After Molecular Absorbent Recirculating System Treatment Integrated With Model for End Stage Liver Disease Model in Patients With Acute-on-Chronic Liver Failure

AIMnThe aim of study was to highlight parameters that in association with Model for End-stage Liver Disease (MELD) provide predictive criteria for long-term survival after treatment with the Molecular Adsorbent Recirculating System (MARS). Two homogenous groups were studied: one treated with standard medical therapy (SMT) and the other, with MARS.nnnMATERIALS AND METHODSnTwenty acute-on-chronic liver failure patients on the waiting list for liver transplantation and affected by alcoholic cirrhosis with similar MELD scores (20-29) were evaluated for 7 days from inclusion and for 6-month survival. Ten patients (seven males and three females) were treated with MARS. Their mean age was 48.5 years (range = 35-61). The number of MARS applications was six for 6 consecutive days, and the length of the applications was 8 hours. Ten other patients (seven males and three females) were treated with SMT, including prophylaxis against bacterial infections and judicious use of diuretics. The precipitating factors were also treated appropriately. The mean age of the patients was 51 years (range = 37-64). All the variables that were significant upon univariate analysis were enrolled in a receiver operating characteristic analysis, with the intention to detect predictive parameters for patient death at 6 months. We considered a significant area under curve (AUC) value to be greater than 0.5.nnnRESULTSnAmong 11 patients who died within 6 months there were in the MARS group and eight in the SMT group: the 3- and 6-month patient survival rates were 90% and 70% versus 30% and 20% in the two groups, respectively. Nine measures resulted in an AUC > 0.5: DeltaMELD; interleukin (IL)-8; IL-6; tumor necrosis factor- alpha, MELD score; creatinine, bilirubin international normalized ratio (INR) and cardiac index. DeltaMELD and postoperative IL-8 concentrations showed better results (AUC = 0.899), followed by postoperative creatinine (AUC = 0.879), postoperative cardiac index (AUC = 0.833), and postoperative INR (AUC = 0.818). Postoperative creatinine showed the best sensitivity (100%), while IL-8, the best specificity (88.9%).nnnCONCLUSIONnA combination of biochemical and clinical variables probably represent the best way to predict the survival of patients, allowing physicians to select the best therapies for each patient.

Combined Liver-Kidney Transplantation in Polycystic Disease: Case Reports

Polycystic disease causes a progressive decrease in renal function and liver degeneration. The progression of the disease evolves separately between organs and transplantation options vary: simultaneous or sequential liver-kidney transplantation or single-organ transplantation. From September 2006 to June 2007 3 combined liver kidney transplantations (CLKT) were performed for polycystic disease with end-stage renal disease: 2 with polycystic liver disease, and 1 with hepatic failure due to congenital hepatic fibrosis. The widest dimensions of the polycystic liver of 50 and 60 cm diameter were due to extensive cystic degeneration. We performed 1 simultaneous CLKT and 2 sequential transplantations: 1 liver after kidney, and 1 kidney after liver. At present all patients are alive with 100% graft function. Median creatinine level at discharge was 0.9 mg/dL (ranges, +/-0.2). Good liver graft function was reported in all 3 cases. Transplant benefit in polycystic liver-kidney disease has been already demonstrated; conservative surgical options may result in a high incidence of complications in highly involved polycystic livers. Delaying transplantation results in a more difficult surgical technique, a higher rate of postoperative complications, and a disturbance of optimal graft retrieval because of the worse preoperative condition of the patients.

Minimization of immunosuppressive therapy and immunological monitoring of kidney transplant recipients with long-term allograft survival

Incidence of cardiovascular complications, cancers and chronic allograft nephropathy (CAN) suggests reduction of immunosuppressive dosages. Some studies analyzed the effects of minimization of immunosuppression until the avoidance of immunosuppressive drugs. However minimization seems to be related to a higher incidence of acute rejection. Induction of tolerance after transplantation and use of immunological tests that could monitor the immune reactivity are required. The aim of this study is to evaluate immunological state in a group of recipients after deceased and living donor kidney transplantation and to minimize immunosuppressive therapy monitoring simultaneously clinical and immunological parameters. We analyzed 41 patients, 38 from deceased donors and 3 from living donor kidney transplantation. All patients were treated with triple immunosuppressive therapy: cyclosporine or sirolimus or tacrolimus, mycophenolate mofetil and steroids. In all recipients the presence of CD8+CD28- T suppressor cells (Ts) was analyzed. Patients were divided in 2 groups, according to the presence of Ts. In patients with Ts, (Group A, n=19), mycophenolate mofetil (MMF) was progressively reduced and then stopped. Steroids were subsequently reduced and then interrupted, maintaining an immunosuppressive therapy with low doses of calcineurin inhibitors (CNI) or sirolimus (SIR). 22 patients were without presence of Ts: we enrolled for the study only patient acute rejection free, without proteinuria and with creatinine levels stable (Group B, n=19). In these patients, MMF was reduced and then stopped, while steroids were decreased to 5 mg at alternate days, maintaining CNI or SIR at medium therapeutic dosages (minimized therapy). Patient and graft overall survival in Group A and in Group B were respectively at 100% and 94.7%. Incidence of acute rejection was respectively at 0% in group A and 15.7% in Group B. Presence of episodes of acute rejection in Group B confirms risk of later minimization of steroids and the relevance of the analysis of recipient immunological reactivity before modification of immunosuppressive therapy. A careful evaluation of recipient immune reactivity with the presence of T regulatory cells can allow adequate and personalized immunosuppressive regimens, without high risks of acute rejection.

Preoperative donor scores and postoperative early measures of graft function: relevance to the outcome of liver transplantation.

BACKGROUNDnSeveral donor and recipient parameters play a role in the determination of post-liver transplant allograft function. The identification of prognostic indices presents great implications for correct allocation of donors and more targeted recipient management. The aim of our review was to detect the role of preoperative scoring systems and early postoperative measures of graft function as predictive factors for the development of graft failure and recipient death.nnnMETHODSnWe stratified a cohort of 97 patients in two groups according to a 1-year functional (Group A; n = 72) versus non-functional (Group B; n = 25) status of the allograft.nnnRESULTSnPatients in group B showed higher preoperative Model for End-stage Liver Disease (MELD) values, longer warm ischemia times, reduced bile outputs and increased peak values of transaminases and INR content within the first 3 days after transplantation. Group B showed 48% of patients with initial poor graft function. The parameters which resulted in a significant prediction of graft loss by multivariate analysis were MELD (P = .012); postoperative day 1 serum alanine aminotransferase (ALT) (P < .0001) and day 3 ALT (P = .003). The predictive factors for patient death were postoperative day 1 serum ALT (P < .0001) and day 3 ALT (P = .001).nnnCONCLUSIONSnMELD score was a useful preoperative parameter for the prediction of post-transplant graft survival. Early ALT values predicted both graft and recipient survivals. Minimization of parameters related to their peaks (warm ischemia time) may improve graft and patients survival rates.

Management of Sepsis During MARS Treatment in Acute on Chronic Liver Failure

INTRODUCTIONnThe aim of our study was a 30-day follow-up of the use of early detection of endotoxin by the endotoxin activity assay (EAA) for patients with acute liver failure superimposed on chronic liver disease (AoCLF) and treated with polymyxin-B hemoperfusion-based (PMX-DHP) treatment and albumin dialysis in the molecular adsorbent recirculating system (MARS).nnnMATERIALS AND METHODSnFrom February 2008 to July 2010, we evaluated 10 AoCLF patients experiencing systemic inflammatory response syndrome (SIRS) in association with suspected infection and an EAA-positive test (>0.60). These patients awaiting liver transplantation (OLT) showed similar Model End-Stage Liver Disease (MELD) scores (range, 19-25) and encephalopathy grade ≤ 2. Five patients received therapy to remove endotoxins with PMX-DHP with MARS treatment for liver failure (group A); the other 5 patients received MARS treatment only (group B).nnnRESULTSnTwo PMX-DHP treatments were performed in 4 group A patients (average EA=0.66 [range, 0.61-0.70]) and 3 treatments for 1 patient (EA=0.92). All 5 subjects underwent an average of 4 MARS treatments (range, 3-5). At the end of therapy, the median EA level was 0.42 (range, 0.37-0.48). As reported in the literature, we achieved a significant improvement in liver and kidney functions using MARS. Measurements of lactate, interleukin (IL)-6, and tumor necrosis factor (TNF)-α were significantly improved among patients treated with the extracorporeal therapies. At 30 days of observation, all 5 patients treated with MARS plus PMX-DHP are alive. In group B, a mean of 7.5 MRAS treatments were performed. We observed an improvement in hemodynamic and liver functions with reduced levels of proinflammatory cytokines and lactates in 4 patients. One patient showed no improvement in clinical status with the development of sepsis and subsequent multiorgan failure after 24 days.nnnCONCLUSIONnThe possibility of an early diagnosis using the EAA in AoCLF patients could prevent the progression of the sepsis cascade. The use of PMX-DHP and MARS in these patients, could lead to resolution of clinical status in a short time.

Early Urine Output Predicts Graft Survival After Kidney Transplantation

BACKGROUNDnIn kidney transplantations, the identification of early postoperative parameters with high predictive power for the development of late allograft dysfunction has important implications for clinical practice. This study sought to determine these parameters in a single-center cohort.nnnMETHODSnWe studied 82 deceased donor renal transplantation. We assessed the following measures: dialysis-dependent delayed graft function (ddDGF), extended DGF, serum creatinine level at day 7, creatinine reduction ratio at day 7, urine output at day 1 and at day 7 posttransplantation (UO7).nnnRESULTSnOnly UO7 showed a significant result upon multivariate analysis (P < .0001). It was less influenced by dialysis with respect to measures based upon serum creatinine. By Receiver Operating characteristic (ROC) analysis, it showed an elevated area under the curve (0.811), with a cut-off value of 500 mL/24 h, showing high sensitivity (98.5%).nnnCONCLUSIONSnUO7 may be of clinical utility to assess the risk for subsequent renal dysfunction.

Does Caval Reconstruction Technique Affect Early Graft Function after Liver Transplantation? A Preliminary Analysis

BACKGROUNDnIn the past decades, the inferior vena cava (IVC) reconstruction technique has undergone several evolutions, such as biopump, piggyback technique (PB), and laterolateral approach (LLPB). Several advantages are reported comparing the PB technique to biopump use. However, comparison between PB and LLPB has not been as well investigated. The aim of this study was to compare the results in terms of immediate graft function and intermediate graft survival among 3 subgroups characterized by distinct caval reconstruction techniques.nnnMETHODSnWe retrospectively analyzed a cohort of 200 consecutive adult patients who underwent liver transplantation from January 2001 to December 2009. The patients were stratified according to 3 caval reconstructive techniques: biopump (n=135), PB (n=32) and LLPB (n=33).nnnRESULTSnThe LLPB group showed the shortest cold and warm ischemia times and the best immediate postoperative graft function. Survival analysis revealed LLPB patients to present the best 1-year graft survival rates: namely, 90.9% versus 75.0% and 74.1% among the PB and biopump groups, respectively (log-rank tests: LLPB vs biopump: P=.03; LLPB vs PB: P=.05). In our experience, LLPB showed the best graft survivals with an evident reduction in both cold and warm ischemia times. However, it is hard to obtain an irrefutable conclusion owing to the retrospective nature of this study, the small sample, and the different periods in which the groups were transplanted.nnnCONCLUSIONSnLLPB technique was a safe procedure that minimized the sequelal of ischemia-reperfusion damage. This technique yielded results superior to venovenous bypass. No definitive conclusions can to be obtained in this study comparing classic PB or LLPB.

Delayed Graft Function Decreases Early and Intermediate Graft Outcomes After Expanded Criteria Donor Kidney Transplants

Use of expanded criteria donors (ECD) has increased worldwide in previous years because of the donor scarcity. However, ECD are related to a greater risk of complications and shorter graft longevity. Delayed graft function (DGF) which impacts renal graft survival, represents one of the most common complications posttransplantation. The purpose of this study was to analyse DGF incidence among ECD kidneys and its role on early and intermediate recipient and graft survivals. We prospectively analyzed 46 ECD cases divided as group A (absence of DGF; n = 23) and B (DGF; n = 23). Group B was composed of older donors (P = .033) with longer cold ischemia times (P = .017), and greater incidences of acute rejection episodes (ARE) (P < .0001). Comparing group A with group B, we observed 1-year and 3-year overall recipient survivals to be 95.7% and 95.7% versus 91.3% and 91.3%, respectively (P = not significant). Censored 1-year and 3-year overall graft survivals were 100% and 92.9% versus 85.6% and 79.9%, respectively (P = .026). Analyzing the patients with DGF without (n = 9) versus with concomitant ARE (n = 14), no differences were noted in recipient and graft survivals. The incidence of DGF was strictly related to increased donor age, greater cold ischemia time, and presence of an ARE while DGF did not have a role in recipient survival, it reduced, graft survival. Concomitant ARE was not related to an impaired graft function.

Simultaneous pancreas-kidney transplantation: a single-center experience and prospective analysis.

In patients with end-stage chronic kidney disease (CKD) and type 1 diabetes mellitus (DM 1), simultaneous pancreas-kidney (SPK) transplantation is currently considered the gold standard therapy. The aim of this study was to analyze and report the long-term clinical outcomes of the 23 SPK transplantations performed at our institution over an 84-month period (January 1, 2000 to December 31, 2006). A prospective analysis of these patients included donor, recipient, and transplantation characteristics. The only requirements for transplantation were blood group compatibility and a negative cross-match. Bladder drainage via pancreaticoduodenocystostomy was performed in all of the patients. Due to a pulmonary embolus 1 patient (4.3%) died at 2 months. The actuarial patient survival rates at 3 months and 1, 3, and 5 years were 95.6%. Causes for the renal graft loss were chronic allograft nephropathy in 3 cases (13%) and death of the patient in 1 case (4.3%). The actuarial censored renal allograft survival rates at 3 months and at 1 year were 100%, and at 3 and 5 years were 91.3%. Causes for the renal graft loss were chronic rejection in 1 case (4.3%) and patient death in 1 case (4.3%). The actuarial censored pancreatic allograft survival rates at 3 months and at 1 and 3 years were 100%, and at 5 years was 95.6%. The results of this work add further evidence that SPK is the gold standard therapy for selected patients with end-stage CKD due to DM 1.