Analysis of risk factors for early hepatic artery thrombosis after liver transplantation. Possible contribution of reperfusion in the early morning.

BACKGROUND: Since the incidence of myocardial infarction and other cardiovascular ischaemic events is highest in early morning, on account of a relative hypercoagulable state occurring in this time period, an attempt was made to test whether reperfusion of the hepatic artery at this time of the day, at liver transplantation, produces an increased risk of early thrombosis. METHODS: The records of 255 consecutive patients receiving a first transplant for chronic liver disease were retrospectively analysed. As possible risk factors, for early post-operative thrombosis (<30 days from transplantation), several medical and surgical parameters were taken into consideration. Arterial reperfusion was considered to have taken place at a time of high coagulability when occurred between 6.00 a.m. and 10.00 a.m. on the basis of previous reports. RESULTS: Logistic regression identified donor age (OR for age >60: P=0.017), bench reconstruction of the artery (OR: 5.06, P=0.013) and time of high coagulability at reperfusion (OR 2.93, P=0.087), as independently associated with early hepatic artery thrombosis. CONCLUSIONS: The present findings identified three independent predictors of early hepatic thrombosis, warranting stricter post-surgical follow-up of patients presenting such conditions. Interestingly, these factors are consistent with arterial reperfusion in the early morning being associated with an increased risk of early hepatic artery thrombosis, suggesting relative coagulative imbalances to provide a contribution in the pathogenesis of this severe complication of liver transplantation.

Portal vein arterialization for the treatment of post resection acute liver failure in the rat.

INTRODUCTION: Hyperoxygenation of the liver has been suggested to improve its regenerative capacity. Thus, this study sought to determine whether an additional supply of oxygenated blood delivered by portal vein arterialization (PVA) was protective against acute liver failure induced by hepatectomy. METHODS: Sprague-Dawley rats (six per each group) were divided to either undergo PVA or be untreated after extended hepatectomy. Liver injury was evaluated by the serum alanine aminotransferase (ALT) levels. Hepatocyte regeneration was assessed by calculating the mitotic index and bromodeoxyuridine staining. The 10-day survival was assessed in separate experimental groups. RESULTS: The pO(2) in portal blood increased significantly following PVA. Serum ALT levels were significantly reduced in arterialized versus nonarterialized rats. PVA promotes liver regeneration. Finally, PVA significantly improved host survival compared to the controls: 90% versus 30%, respectively. CONCLUSION: These data suggested that an additional supply of arterial oxygenated blood through PVA promoted a rapid regeneration, leading to a faster restoration of liver mass after partial hepatectomy in rats. Thus, PVA may represent a novel tool to optimize hepatocyte regeneration.

Successful treatment of CCL4-induced acute liver failure with portal vein arterialization in the rat.

INTRODUCTION: Optimization of the conditions for regeneration of the native diseased liver is a major goal in patients with acute liver failure. This study sought to determine whether portal vein arterialization (PVA), which increases the oxygen supply to the liver, was protective in a rat model of liver failure. METHODS: At 24 hours after CCl(4) intoxication, Sprague-Dawley rats (six per group) were assigned to receive PVA or as controls. We determined blood tests, histology, and 10-day survivals. Hepatocyte regeneration was assessed by the mitotic index and bromodeoxyuridine (BrdU) incorporation. RESULTS: Serum transaminases were significantly lower in PVA-treated rats than in control animals: liver necrosis resolved rapidly after PVA. The BrdU staining and mitotic index were severalfold higher among PVA-treated than in untreated rats. Survival was 100% among rats with PVA and 40% in untreated animals (P < .01). CONCLUSIONS: PVA led to resolution of CCl(4)-induced massive liver necrosis in the rat. This effect was probably mediated by activation of rapid and extensive hepatocyte regeneration. PVA might provide a novel, alternative approach to treat acute liver failure.

Technical aspects of portal vein arterialization for acute liver failure: from rat lab to man.

Survival rates of patients with acute liver failure (ALF) without transplantation are poor. However, many of them die awaiting a transplant because of the donor organ shortage. Supporting these patients until an organ becomes available or until their own liver is able to regenerate itself thus avoiding transplantation is a major goal in their multidisciplinary treatment. Animal experimental studies have shown that portal vein arterialization (PVA) enhances the regenerative capacity of hepatocytes by increasing the oxygen supply to the liver after extended hepatectomy or in toxin-induced ALF models. Furthermore, we have reported the application of PVA in patients with ALF. We herein have described the technical aspects of the PVA procedure both in preclinical models and in man.

The first case of ureteral duplication in a combined liver-kidney transplantation.

AIM: Kidney transplantation with ureteral duplication may represent a doubled risk factor in terms of ureteral stenosis or necrosis with urinary leakage usually from the site of ureteroneocystostomy. The incidence of complete duplication is very low at 0.19%. We report a kidney with ureteral duplication in the specific setting of multiorgan transplantation since it could be considered an adjunctive risk factor for urological complications. METHODS: The recipient was a 67-year old man, suffering from terminal renal insufficiency. He was also affected by HCV-related cirrhosis. The patient had been waiting for the combined transplantation for 27 months and in the last two months his hepatic function dramatically worsened. The donor was a 53-year old man who died of non-traumatic subarachnoid hemorrhage. Good HLA compatibility was observed between donor and recipient. During harvest both kidneys presented a complete ureteral duplication. So the ureters were freed together with a wide cuff of periureteral tissue and dissected distally. No vascular abnormalities were noted during the removal of either kidney. The grafts were flushed with University of Wisconsin solution and stored in the same solution. RESULTS: The liver was reperfused after 9 hours of cold ischemia. Subsequently the kidney was vascularized after 15 hours of cold ischemia. Urine production occurred immediately after revascularization. Two separated ureteroneocystostomies with a single antireflux technique were performed. Cyclosporine and steroids were given. Post-operative course was uneventful and liver and kidney function were normal. The 7-day cystography was normal. The 6, 12, 24 month ultrasonographies showed no signs of hydronephrosis or hydroureter. After 28 months renal cancer was diagnosed and the patient underwent a right nephrectomy. The liver-kidney recipient had excellent hepatic and renal function for 84.7 months. He died of malignancy from de novo tumor. CONCLUSIONS: On the basis of this experience, a kidney with an ureteral duplication, while rare, can be satisfactorily used also in combined liver-kidney transplantation.

Effect of recombinant human leukocyte, fibroblast, and immune interferons on expression of class I and II major histocompatibility complex and invariant chain in early passage human melanoma cells.

Twenty-five early-passage (less than or equal to 8) melanoma cell lines, isolated from ten patients with metastatic melanoma, were analyzed by a combination of serological, immunochemical, and molecular methods for mRNA levels, synthesis, and surface expression of MHC class I and class II antigens prior to and following exposure to recombinant human leukocyte (IFN-alpha A), fibroblast (IFN-beta), and immune (IFN-gamma) interferon. All the cell lines expressed variable levels of HLA class I gene products that were up-regulated to different extents upon exposure to specific interferons (IFNs). HLA class II antigens were expressed in 22 of the 25 melanoma lines and IFN-gamma increased the levels of class II mRNA, protein synthesis, and surface expression in all cultures displaying baseline expression. A significant up-regulation of class II antigen expression by IFN-alpha or -beta, associated with higher levels of class II transcripts and enhanced synthesis, was found only in two early-passage human melanoma cell lines. In three lesions from the same patient which did not constitutively express class II antigens, no expression of these glycoproteins could be induced with any of the IFNs. These results indicate that IFN-gamma does not act as a de novo inducer of class II antigen expression in early-passage human melanoma cell lines. This hypothesis is further supported by analysis of class II-associated invariant chain (Ii) expression, which is expressed and induced by IFNs in a manner similar to that of class II antigens. The present study also indicates that early-passage metastatic melanoma lesions from the same patient are heterogeneous in their de novo expression of major histocompatibility antigens and in their modulation by IFNs.

Red blood cell transfusion in liver transplantation: a case-control study.

INTRODUCTION: We aimed to analyze the influence of intraoperative blood transfusion on postoperative complications and survival and to identify the preoperative variables associated with greater intraoperative bleeding. MATERIALS AND METHODS: Thirty-one elective liver transplantations (OLT) without blood transfusion performed between 1986 and 2002 (group 1) were compared with 62 patients (group 2) who underwent elective OLT with intraoperative transfusion after matching for gender, disease severity, and chronology. RESULTS: The hemoglobin and hematocrit values were significantly greater in group 1 compared to group 2. No significant differences were reported for the other parameters. In particular, the type of surgical technique had no influence on the blood requirement. As expected the nontransfused patients received less autologous packed red blood cells compared with the transfused patients. No differences were observed in either group for mean CIT, ICU and hospital stay, or acute rejection. A significant difference was observed in the number of postoperative infectious episodes, which was higher in group 2 (28 vs 5, P = .01). Graft and patient survivals at 3 months and 5 years did not differ significantly between groups. CONCLUSIONS: OLT without blood transfusion may be achieved in the presence of good recipient conditions. Lower preoperative hemoglobin and hematocrit values were associated with greater intraoperative transfusions.

Preliminary results of a clinical randomized study comparing Celsior and HTK solutions in liver preservation for transplantation.

INTRODUCTION: A prospective, randomized, multicenter, open clinical trial was performed to compare the main liver function tests, postoperative complications, and early graft and patient survival of recipients transplanted with livers preserved in Celsior (CEL) versus histidine tryptophan ketoglutarate (HTK) solutions. METHODS: We analyzed the data from a single center. Forty livers randomized to CEL (n = 20) or HTK (n = 20) preservation solution were perfused in situ via the aorta and portal vein (CEL, 30 mL/kg via portal vein and 60 mL/kg via aorta; and HTK solution, 30 mL/kg via portal vein and 120 mL/kg via aorta). RESULTS: The groups were comparable with regard to donor, graft, and recipient characteristics. The mean cold ischemia time was 458 minutes (range: 203-667 minutes) in CEL and 450 (range: 310-684 minutes) in HTK. The incidence of initial poor function and primary nonfunction in CEL and HTK were (0 vs 1) and (0 vs 1), respectively. No differences were observed for acute rejection. No vascular or biliary complications were reported in either group. The 3-month graft and patient survival rates were 95% and 95% in CEL and 80% and 90% in HTK. The 12-month graft and patient survival rates were 90% and 90% in CEL and 75% and 85% in HTK. CONCLUSIONS: To our knowledge, this is the first report comparing CEL and HTK preservation solutions in clinical liver preservation. Although a greater 1-year graft and patient survival was observed in the CEL group, a definitive evaluation comparing CEL and HTK solutions in clinical preservation must await completion of the trial.

Octogenarian livers successfully transplanted in patients with fulminant hepatic failure.

Although octogenarian livers have been transplanted successfully in elective settings, their safety in the case of fulminant hepatic failure has not yet been reported. From November 1998 to June 2003, we transplanted 3 livers from 80-, 82-, and 86-year-old donors. The donors were hemodynamically stable with an intensive care unit stay ranging from 24-48 hours. Cold ischemia time was from 260 minutes to 526 minutes. Mild macrosteatosis was present in 2 donors. Donor and recipient characteristics as well as posttransplantation evolution were evaluated. Two cases had uneventful courses and all recipients are well at 39, 21, and 5 months, respectively. The second recipient underwent retransplantation at 15 days due to technical complications. Livers from octogenarian donors may be safely used in an emergency to save patients. Age does not represent a limit for individually assessed and highly selected donors.

The mismatch choice in liver transplantation: a suggestion for the selection of the recipient in relation to the characteristics of the donor.

Two hundred seventy-six liver transplants were retrospectively reviewed to analyze 6-month graft survival in relation to the combination of donor quality (standard donor vs nonstandard donor) and risk related to the severity of recipient liver disease low-risk, ie, United Network for Organ Sharing [UNOS] status 3/2b; high-risk, ie, UNOS status 1/2a). The overall 6-month survival rate of 82% was stratified into 4 classes: (1) standard donor to low-risk recipient = 88%; (2) standard donor to high-risk recipient = 86%; (3) nonstandard donor to low-risk recipient = 84%; and (4) nonstandard donor to high-risk recipient = 67%. According to the observed graft survival in the 4 different classes, 2 simulations were performed: the "match simulation" (transplantation of all low-risk recipients using standard donors, and transplantation of all high-risk recipients using nonstandard donors), and the "mismatch simulation" (transplantation of all the high-risk patients using low-risk donors and transplantation of low-risk patients using high-risk donors). The 6-month survival rates, calculated using the match simulation, were 74% and using the mismatch simulation, 84%. The authors suggest that, in the era of marginal donors, the recipient should be selected in relation to the characteristics of the donor according to the mismatch model.

Liver transplantation in fulminant hepatic failure: experience with 40 adult patients over a 17-year period.

INTRODUCTION: To evaluate the influence of pretransplantation recipient and donor prognostic factors on graft-patient survival. MATERIALS AND METHODS: Between April 1986 and June 2003, 40 liver transplantation (LT) procedures to treat fulminant hepatic failure were performed (5.7%). Twenty-one pre-LT recipient and donor variables were retrospectively considered for analysis. RESULTS: The indications for LT were hyperacute (62.5%), acute (35%), and subacute hepatic failure (2.5%). Glasgow Coma Scale scores ranged from <5 in 22 patients to > or =5 in 18 patients. The causes were hepatitis B (n = 21), unknown (n = 10), Amanita phalloides (n = 5), and other (n = 4). The 1-year graft and patient survival rates were 48.3% and 61.3%, respectively. Perioperative and late mortality was 27.5% and 22.5%. The only variable statistically significant for graft survival was waiting list time for LT <48 hours (P = .05). DISCUSSION: Liver transplantation is the best treatment for fulminant hepatic failure, with a 1-year patient survival rate of 61.3%. The short waiting list time has an important role in outcome.

Liver transplantation in recipients with portal vein thrombosis: experience of a single transplant center.

INTRODUCTION: Although portal vein thrombosis (PVT) is no longer considered a contraindication for liver transplantation (OLT), it is still considered a high risk because of the complexity of the surgical procedure. The aim of this study was to evaluate the impact of PVT in the recipient during OLT on intra- and perioperative management and outcome. PATIENTS AND METHODS: Between April 1986 and October 2003, 721 primary OLT included 64 patients (8.8%) with PVT. The underlying liver disease was postnecrotic cirrhosis in most cases (n = 37). Intraoperative (length of surgery, packed red blood cells (PRBC) transfusion requirements, ischemia time, complications) and postoperative parameters (ICU stay and hospitalization time, complications, actuarial graft and patient survival at 1 month and 1 and 5 years) were compared with a control group of patients submitted to OLT without PVT (n = 657). RESULTS: Portal flow was reestablished in 56 patients with thromboendovenectomy, in seven patients with a venous graft from the superior mesenteric vein, and with cavoportal hemitransposition in one case. The average ICU and hospital stay as well as the 1-month and 1- and 5-year patient survivals were not significantly different in the PVT versus the control group. We observed slightly more PRBC transfusions and longer surgery procedures in the PVT group. CONCLUSIONS: Our experience suggests that thromboendovenectomy is the procedure of choice for PVT. The results are good in terms of survival rates and postoperative complications, although the presence of PVT may lead to more technical problems during surgery.

Portal vein arterialization: a new surgical option against acute liver failure?

Survival rates of patients with acute liver failure (ALF) without transplantation are poor. Supporting these patients until an organ becomes available or until their own liver is able to regenerate itself, avoiding transplantation, is a major goal in the treatment of ALF. We report our clinical experience of portal vein arterialization in one case of massive liver necrosis after liver transplantation and in two patients with ALF caused by idiosyncratic drug reaction and mushroom intoxication. Portal vein arterialization, at least in two cases, was a turning point in the course of the disease since a close temporal association between surgery and clinical improvement was clearly evident. We believe that this novel approach, which should promote liver regeneration by providing an additional oxygen supply to the liver, may disclose a new possibility in the treatment of ALF and prompt new clinical and experimental research.

Kidney transplantation combined with other organs: experience of Bologna s. Orsola hospital.

AIM: We report a series of patients who underwent combined heart-kidney transplantation (CHKT) and combines liver-kidney transplantation (CLKT) at a single center. METHODS: From January 1997 to October 2004, 13 CLKT and 2 CHKT were performed. The CLKT indications were as follows: polycystic disease (2), kidney polycystic disease associated with Caroli (1) and cirrhosis-hepatitis C virus (HCVs) (1), chronic glomerulonephritis with cirrhosis-HCV (4), and other diseases (5). From December 2003 to October 2004, 2 patients underwent CHKT for idiopathic cardiomyopathy plus glomerulonephritis and ischemic cardiomyopathy associated with vascular nephritis. RESULTS: In the CLKT group, 1 patient had acute rejection involving both liver and kidney grafts, whereas 1 patient had liver rejection and another 1 had kidney rejection alone. Of the 13 patients, 10 are alive with a mean survival of 583 days (range, 36-2688 days); 2 patients died within 1 month of transplantation (both with polycystic disease) due to ARDS and MOF. Another patient died 6 years and 9 months after CLKT of metastasis from a de novo tumor. In the CHKT group, no patient suffered heart-kidney rejection. They are all alive at 333 and 116 days, with heart and kidney allografts functioning well. CONCLUSION: In the CLKT group, the worst results were for patients with polycystic disease, in whom a more rigorous selection is necessary because of greater technical difficulties. For the remaining patients we had acceptable complications and excellent long-term results. In selected cases, CHKT can provide long-term graft function and patient survival. Our experience indicates that end-stage kidney failure combined with liver or heart failure does not necessarily preclude dual-organ transplantation.

Chemiluminescent real time imaging of post-ischemic oxygen free radicals formation in livers isolated from young and old rats.

Oxygen free radicals generation is a major cause of liver injury during reperfusion. Luminescence analysis has been recently proposed to measure free radical generation by isolated cells or organs, but it allows only global tissue luminescence. Using a special Saticon videocamera with image intensifier we aimed to visualize and localize oxygen free radical generation in isolated perfused livers exposed to an oxydative stress. Livers isolated from rats aged 4 and 30 months were exposed to ischemia/reperfusion; photons emission by the organs was continuously recorded. Lucigenin was utilized as a chemiluminigenic probe to assess superoxide anion generation. In both groups, chemiluminescence was not detectable during ischemia, while it was observed after reperfusion. Photons emission started after few minutes of reperfusion, was maximal after 15-20 min and disappeared within 50-60 min. Chemiluminescence emitted by livers from younger rats however, was significantly higher when compared to chemiluminescence emitted by organs isolated from old rats (0.8 +/- 0.1 vs 0.44 +/- 0.08 photons x 10(5)/s, respectively, after 15 min; p < .01). The superimposition of chemiluminescent and live image permitted to determine the regional production rate and distribution of photons. In conclusion, the age of the rats influences significantly the amount of oxyradicals produced in the liver during post-ischemic reperfusion. The method described, allowing the visualization in real time of oxygen free radicals generation on the surface of isolated intact organs, represents a novel and potent tool for the study of oxidative stress.

Abstension from treatment of low-level pp65 cytomegalovirus antigenemia after liver transplantation: a prospective study.

BACKGROUND: Ganciclovir is a highly effective and relatively safe drug to treat cytomegalovirus (CMV) infection in liver transplant patients; CMV resistance to ganciclovir is progressively emerging due to the extensive use of the drug in transplant and AIDS patients; CMV pp65 antigenemia allows early diagnosis of CMV infection and quantitation of the viral load; preemptive antigenemia-guided therapy of CMV infection can prevent CMV disease but the threshold of antigenemia value above which treatment has to be instituted is unclear. METHODS: To demonstrate the safety of abstention from preemptive treatment in the presence of low levels of antigenemia 77 consecutive liver transplant recipients were prospectively evaluated. Antigenemia was tested twice a week from transplantation until discharge, then once a week until the third postoperative month. In absence of risk factors for CMV disease, namely donor positive/recipient negative CMV serology, treatment with antibodies to lymphocytes and retransplantation, only patients with antigenemia of more than 50 or symptoms possibly related to CMV infection had preemptive treatment. RESULTS: A total of 32 patients had at least one positive antigenemia test with a value less than 50; 22 (68.7%) spontaneously cleared the virus, 3 were treated with i.v. ganciclovir for the presence of fever, and the other 7 (21,8%) progressed to values of antigenemia of more than 50 and were treated even if asymptomatic. No CMV disease was observed in these patients. CONCLUSION: CMV antigenemia less than 50 in liver transplant recipients with low and intermediate risk for CMV disease does not mandate preemptive ganciclovir treatment. Close surveillance with repeated determination of antigenemia until its negativization and careful clinical and laboratory monitoring is advisable.

Prosthesis jump graft: an unusual arterial reconstruction in liver transplantation.

The authors present a case of arterial jump graft using a number 9 Goretex prosthesis (FEP ringed vascular graft; W.I. Gore Associates Inc.-Delaware, Flagstaff, AZ) with an excellent outcome 3 years after the transplant. The prosthesis was necessary because of the impossibility of using the donor iliac arterial grafts due to the presence of widespread atherosclerotic damage.

Randomized trial of cyclosporine microemulsion (neoral) versus conventional cyclosporine in liver transplantation: MILTON study. Multicentre International Study in Liver Transplantation of Neoral.

BACKGROUND: The new microemulsion formulation of cyclosporine (Neoral) has been developed in an effort to improve the reliability of drug absorption. The objectives of this study were to assess the efficacy, safety, and tolerability of Neoral compared to the original formulation (Sandimmun) in liver transplant recipients. METHODS: In a double-blind, parallel group study conducted in 28 centers across Europe and the United States, patients receiving primary orthotopic liver allografts were randomized within 24 hr of transplantation, 198 to Neoral and 192 to Sandimmun. Patients with and without T-tube biliary drainage were included. Postoperatively, all patients also received intravenous (i.v.) cyclosporine, together with prednisolone and azathioprine. Antibody induction was excluded. Efficacy measures were rejections, graft failure, patient survival, and the efficacy of the study medication in achieving the desired cyclosporine blood levels. Safety was assessed by reported adverse events, blood pressure, serum creatinine, and other routine laboratory measurements. RESULTS: Kaplan-Meier analyses showed that the Neoral group performed better than the Sandimmun group, with the estimates for patients free of treated rejection and histologically confirmed rejection either showing or approaching statistical significance at the 5% level. By 52 weeks, 5.8% (95% confidence limits: -4.4-15.9%) fewer patients required treatment of acute rejection in the Neoral group. The proportion of patients experiencing at least one treated rejection episode by 2 weeks was 29.8% for Neoral and 43.2% for Sandimmun. For histologically confirmed rejection, these proportions were 32.8% and 44.3%, respectively. The proportion of patients experiencing at least one steroid-resistant rejection was 2.0% for Neoral and 6.3% for Sandimmun at week 2, and 3.0% and 9.9%, respectively, at week 3. All these differences were significant at P<0.05. By 52 weeks, graft failure was 6.3% on Neoral and 11.4% on Sandimmun, with respective patient survival figures of 85.4% and 85.8%. The median duration of the initial episode of i.v. cyclosporine was 4.0 days for Neoral, compared to 6.5 days for Sandimmun (P<0.001). Within the first 2 weeks, a larger percentage of patients in the Neoral group reached the lower target level of cyclosporine (P< or =0.01). The weight-adjusted daily doses of study medication were lower in the Neoral group (median dose: 4.86 vs. 5.42 mg/kg/day, P=0.001), but the blood levels of cyclosporine showed no difference. For those with a T-tube, more of the patients on Neoral remained free of treated rejection throughout the study period (P=0.042, Wilcoxon). By week 2, 44.9% of these patients in the Sandimmun group required treatment for rejection compared to 30.2% in the Neoral group (P=0.007). There was no significant difference between the groups for serum creatinine, blood pressure, other biochemical and hematological variables, or reported adverse events. CONCLUSIONS: In liver transplantation in the normal clinical setting, the pharmacokinetic advantages of Neoral translate into clinical superiority over Sandimmun without a negative impact on safety. Recent data indicate that it is not optimal to use i.v. cyclosporine initially in this type of study, but the benefit was seen despite this. In keeping with the previous pharmacokinetic studies, patients managed by T-tube biliary drainage, and hence with no or limited bile available in the gastrointestinal tract, did particularly well with Neoral.

Kidney preservation with university of Wisconsin and Celsior solution: a prospective multicenter randomized study.

BACKGROUND: Although the University of Wisconsin (U.W.) solution continues to be the most commonly used for intra-abdominal organs, a new solution, Celsior, already used for heart and lungs, has been proposed for kidney and liver preservation. The aim of this research was to assess the effect of Celsior as compared with U.W. on immediate graft function and a 2-year follow-up of kidney transplants. METHODS: A prospective multicenter randomized study was designed to evaluate the efficacy of the Celsior solution in the clinical preservation of the kidney. In this report, we present the data collected as of September 2000. One hundred donors were included in the trial resulting in 187 renal transplants. Ninety-nine kidneys were stored in Celsior solution and 88 in U.W. solution. The groups were comparable with regard to donor and recipient characteristics. RESULTS: Delayed graft function occurred in 31.3% of the Celsior group and in 33.9% of the U.W. group (P=n.s.). Mean serum creatinine levels and mean daily urinary output were also comparable. Two year graft survival in kidneys preserved with Celsior was 84% as compared with 75% for U.W.-preserved kidneys without any significant statistical difference. CONCLUSIONS: Our data show that the preservation of kidneys in Celsior solution in a clinical setting is equivalent to that of U.W. solution. When using Celsior during multiple-organ donor harvesting it would be possible to perform an in situ flush of all intra-abdominal and intrathoracic organs with a single cold storage solution.

Improved clinical outcomes for liver transplant recipients using cyclosporine monitoring based on 2-hr post-dose levels (C2).

BACKGROUND: A prospective, open-label, study was conducted at 29 centers in 9 countries, involving 307 de novo liver transplant patients to compare the clinical usefulness of monitoring 2-hr post-dose cyclosporine (CsA) levels (C2) with conventional trough cyclosporine blood levels (pre-dose) (C0). METHODS: Neoral oral therapy was initiated at 15 mg/kg/day and dose adjusted according to predetermined C2 or C0 target level ranges. The primary efficacy variable was treatment failure at 3 months, where evaluation was based on a composite endpoint of biopsy-proven rejection, treatment for rejection, graft loss, death, or premature withdrawal/discontinuation from the study. RESULTS: Baseline characteristics were similar between groups. Graft loss at 12 weeks (retransplantation or death) occurred in 6.8% C2 and in 7.0% C0 patients. Overall incidence of treated acute rejection was lower for C2 (23.6%) than C0 patients (31.6%) (P=0.144, Cochran-Mantel-Haenszel [CMH] test). In hepatitis C virus (HCV)-negative patients, the incidence of rejection in the C2 group was significantly less than in the C0 group (21.2% vs. 33.0%; P<0.05), whereas in HCV-positive patients, the rejection rate was similar in both groups (26.7% for C2 group vs. 27.3% for C0 group: P=0.81). C2 patients (n=16) who reached minimum target CsA levels by day 3 had a notably low incidence of rejection (12.5%), whereas there was no difference in the incidence of rejection in C0 patients, irrespective of time to reach target level. For biopsy-proven acute rejections (21.6% for C2 vs. 30.4% for C0), the incidence of moderate and severe histological diagnosis was significantly lower in the C2 group than in the C0 group (47% vs. 73%; P=0.01). Safety profiles were similar between the two groups, with few patient withdrawals due to adverse events (9.5% for C2; 7.0% for C0). CONCLUSIONS: Using C2 monitoring, the overall incidence of acute cellular rejection was lower compared with the C0 group, and the histological severity of acute rejections was shown to be significantly milder for the C2 group, indicative of good long-term prognosis. These data demonstrate that the use of C2 monitoring is superior to C0 and results in a reduction in the incidence and severity of acute cellular rejection without detrimental effect on the drug safety profile.