Predisposing Factors of Diminished Survival in Simultaneous Liver/Kidney Transplantation

Since the adoption of the Model for End‐Stage Liver Disease, simultaneous liver/kidney transplants (SLKT) have substantially increased. Recently, unfavorable outcomes have been reported yet contributing factors remain unclear. We retrospectively reviewed 74 consecutive adult SLKT performed at our center from 2000 to 2010 and compared with kidney transplant alone (KTA, N = 544). In SLKT, patient and death‐censored kidney graft survival rates were 64 ± 6% and 81 ± 5% at 5 years, respectively (median follow‐up, 47 months). Multivariable analyses revealed three independent risk factors affecting patient survival: hepatitis C virus positive (HCV+, hazard ratio [HR] 2.9, 95% confidence interval [CI] 1.1–7.9), panel reactive antibody (PRA) > 20% (HR 2.8, 95% CI 1.1–7.2) and female donor gender (HR 2.9, 95% CI 1.1–7.9). For death‐censored kidney graft survival, delayed graft function was the strongest negative predictor (HR 8.3, 95% CI 2.5–27.9), followed by HCV+ and PRA > 20%. The adjusted risk of death‐censored kidney graft loss in HCV+ SLKT patients was 5.8 (95% CI 1.6–21.6) compared with HCV+ KTA (p = 0.008). Recurrent HCV within 1 year after SLKT correlated with early kidney graft failure (p = 0.004). Careful donor/recipient selection and innovative approaches for HCV+ SLKT patients are critical to further improve long‐term outcomes.     

Immunosuppression with calcineurin inhibitors with respect to the outcome of HCV recurrence after liver transplantation: results of a meta-analysis.

A controversy exists over whether the outcome of a hepatitis C virus (HCV)-infection-related liver transplant differs based on the calcineurin inhibitor (CNI) used. We have performed a systematic review and a subsequent meta-analysis evaluating tacrolimus (Tac)-based vs. cyclosporine A-based immunosuppression in HCV-infected liver transplant recipients. Searches were conducted to locate randomized controlled trials comparing Tac vs. cyclosporine A. Data on HCV liver transplant recipients were obtained, independently of whether the study was specifically designed for patients with this disease or not. A fixed effects model was used for statistical pooling of the relative risks (RR) for the different outcomes. A total of 5 articles (366 patients) fulfilled the inclusion criteria. Statistically significant differences between Tac-based vs. cyclosporine A-based therapies were not found for mortality (P = 0.11; RR = 0.72; 95% confidence interval [CI], 0.49-1.08), graft survival (P = 0.37; RR = 0.86; 95% CI, 0.61-1.21), biopsy-proven acute rejection (P = 0.65; RR = 0.91; 95% CI, 0.61-1.36), corticoresistant acute rejection (P = 0.26; RR = 2.25; 95% CI, 0.55-9.29), and fibrosing cholestatic hepatitis (P = 0.92; RR = 0.96; 95% CI, 0.41-2.26). In 1 study, no differences were detected regarding severe fibrosis at 1 yr. In conclusion, patient and graft survivals in HCV-positive liver transplant patients are similar independently of the CNI selected as basic immunosuppressant. Unfortunately, data on the severity of recurrence and effect on viremia are scarce. Well-designed randomized prospective studies are needed to determine whether there are differences between the 2 CNIs regarding these specific variables.     

Outcomes of liver transplant recipients with hepatitis C and human immunodeficiency virus coinfection

Hepatitis C virus (HCV) is a controversial indication for liver transplantation (LT) in human immunodeficiency virus (HIV)-infected patients because of reportedly poor outcomes. This prospective, multicenter US cohort study compared patient and graft survival for 89 HCV/HIV-coinfected patients and 2 control groups: 235 HCV-monoinfected LT controls and all US transplant recipients who were 65 years old or older. The 3-year patient and graft survival rates were 60% [95% confidence interval (CI) = 47%-71%] and 53% (95% CI = 40%-64%) for the HCV/HIV patients and 79% (95% CI = 72%-84%) and 74% (95% CI = 66%-79%) for the HCV-infected recipients (P < 0.001 for both), and HIV infection was the only factor significantly associated with reduced patient and graft survival. Among the HCV/HIV patients, older donor age [hazard ratio (HR) = 1.3 per decade], combined kidney-liver transplantation (HR = 3.8), an anti-HCV-positive donor (HR = 2.5), and a body mass index < 21 kg/m(2) (HR = 3.2) were independent predictors of graft loss. For the patients without the last 3 factors, the patient and graft survival rates were similar to those for US LT recipients. The 3-year incidence of treated acute rejection was 1.6-fold higher for the HCV/HIV patients versus the HCV patients (39% versus 24%, log rank P = 0.02), but the cumulative rates of severe HCV disease at 3 years were not significantly different (29% versus 23%, P = 0.21). In conclusion, patient and graft survival rates are lower for HCV/HIV-coinfected LT patients versus HCV-monoinfected LT patients. Importantly, the rates of treated acute rejection (but not the rates of HCV disease severity) are significantly higher for HCV/HIV-coinfected recipients versus HCV-infected recipients. Our results indicate that HCV per se is not a contraindication to LT in HIV patients, but recipient and donor selection and the management of acute rejection strongly influence outcomes.     

Long-term results of a prospective randomized trial comparing tacrolimus versus cyclosporine in African– American recipients of primary cadaver renal transplant

The ideal immunosuppressive treatment for African-American kidney transplant recipients has not been established. We performed a long-term prospective randomized trial comparing the results of tacrolimus (TAC) and cyclosporine (CSA) in the African-American population. Thirty-five African-American primary cadaveric renal transplant (CRT) recipients were enrolled in the study. Group I (n = 14) received TAC and group II (n = 21) received CSA; mean follow up was 78 months. We found no difference in patient/graft survival rates between the groups. Twelve patients in the CSA group were converted to TAC, mostly because of hypercholesterolemia or as a rescue for an acute rejection episode. Significant lower creatinine and cholesterol levels were seen at 1 year post-transplant, but this difference lost significance at 3 and 5 years, possibly because of conversion of most patients from CSA to TAC. In conclusion, African-American recipients of primary CRTs can achieve excellent long-term results with TAC-based immunosuppression.     

Outcome of HCV/HIV‐Coinfected Liver Transplant Recipients: A Prospective and Multicenter Cohort Study

Eighty‐four HCV/HIV‐coinfected and 252‐matched HCV‐monoinfected liver transplant recipients were included in a prospective multicenter study. Thirty‐six (43%) HCV/HIV‐coinfected and 75 (30%) HCV‐monoinfected patients died, with a survival rate at 5 years of 54% (95% CI, 42–64) and 71% (95% CI, 66 to 77; p = 0.008), respectively. When both groups were considered together, HIV infection was an independent predictor of mortality (HR, 2.202; 95% CI, 1.420–3.413 [p < 0.001]). Multivariate analysis of only the HCV/HIV‐coinfected recipients, revealed HCV genotype 1 (HR, 2.98; 95% CI, 1.32–6.76), donor risk index (HR, 9.48; 95% CI, 2.75–32.73) and negative plasma HCV RNA (HR, 0.14; 95% CI, 0.03–0.62) to be associated with mortality. When this analysis was restricted to pretransplant variables, we identified three independent factors (HCV genotype 1, pretransplant MELD score and centers with <1 liver transplantation/year in HIV‐infected patients) that allowed us to identify a subset of 60 (71%) patients with a similar 5‐year prognosis (69%[95% CI, 54–80]) to that of HCV‐monoinfected recipients. In conclusion, 5‐year survival in HCV/HIV‐coinfected liver recipients was lower than in HCV‐monoinfected recipients, although an important subset with a favorable prognosis was identified in the former.     

The impact of hepatitis C virus donor and recipient status on long-term kidney transplant outcomes: University of Wisconsin experience

Singh N, Neidlinger N, Djamali A, Leverson G, Voss B, Sollinger HW, Pirsch JD. The impact of hepatitis C virus donor and recipient status on long‐term kidney transplant outcomes: University of Wisconsin experience. Abstract: The survival benefit of transplanting hepatitis C (HCV)‐positive donor kidneys into HCV‐positive recipients remains uncertain. The purpose of this study was to assess the effect of HCV‐status of the donor (D) kidney on the long‐term outcomes in kidney transplant recipients (R). We evaluated 2169 consecutive recipients of deceased‐donor kidney transplants performed between 1991 and 2007. The following HCV cohorts were identified: D?/R? (n = 1897), D?/R+ (n = 59), D+/R? (n = 118), and D+/R+ (n = 95). Patients were followed for a mean of 6.02 (standard deviation = 4.26) yr. In a mulitvariable Cox‐proportional hazards model, D+/R+ cohort had significantly lower patient survival (adjusted‐hazard ratio [HR] 2.1, 95% CI [1.4–2.9]) with respect to the reference D?/R? group, whereas mortality was not increased in D?/R+ group. The rate of graft loss was increased in both D+/R+ and D?/R+ but was comparable with each other (adjusted‐HR 1.8, 95% CI [1.4–2.5]) vs. adjusted‐HR 2.0, 95% CI [1.4–2.8], respectively). D?/R+ cohort experienced significantly higher rate of rejection (adjusted‐HR 1.7, 95% CI [1.2–2.5]) and chronic allograft nephropathy (adjusted‐HR 2.1, 95% CI [1.2–3.7]). Neither donor nor recipient HCV‐status impacted the risk of recurrent or de novo GN. Transplanting HCV‐positive kidneys as opposed to HCV‐negative kidneys into HCV‐positive recipients provided similar graft survival but compromised patient survival in the long term.     

Cyclosporine A Protects Against Primary Biliary Cirrhosis Recurrence After Liver Transplantation

Primary biliary cirrhosis (PBC) reoccurs in a proportion of patients following liver transplantation (LT). The aims of our study were to evaluate the risk factors associated with PBC recurrence and determine whether recurrent disease constitutes a negative predictor for survival. One hundred and eight patients receiving LT for end‐stage PBC were studied. Recurrent disease was diagnosed in 28 patients (26%). Probability of recurrent PBC at 5 years was 13% and 29% at 10 years with an overall incidence of 3.97 cases per 100 patient years. By univariate Cox analysis use of tacrolimus (HR 6.28, 95% CI, 2.44–16.11, p < 0.001) and mycophenolate mofetil (HR 5.21, 95% CI, 1.89–14.33, p = 0.001) were associated with higher risk of recurrence; whereas use of cyclosporine A (CsA) and azathioprine were associated with reduced risk of recurrence (HR 0.13, 95% CI 0.05–0.35, p < 0.001 and HR 0.27, 95% CI 0.11–0.64, p = 0.003, respectively). In the multivariate Cox analysis, only CsA was independently associated with protection against recurrence (HR 0.17, 95% CI 0.06–0.71, p = 0.02). Five‐year probability of survival was 83% and 96%, in patients without and with recurrence (log‐rank test, p = 0.3). Although PBC transplant recipients receiving CsA have a lower risk of disease recurrence, the development of recurrent PBC did not impact on long‐term patient survival.     

Impact of immunosuppressive regimen on survival of kidney transplant recipients with hepatitis C

BACKGROUND: Hepatitis C virus (HCV) infection is common among end-stage renal disease patients receiving hemodialysis and a kidney transplant. HCV-positive kidney transplant recipients have worse clinical outcomes than those who are HCV negative. The optimal immunosuppressive regimen in this group of patients remains uncertain. METHODS: Using data obtained from the Organ Procurement and Transplantation Network/Scientific Registry of Transplant Recipients, we studied the impact of induction and maintenance immunosuppression on risk of patient death, with death-censored graft failure and death with a functioning graft as secondary endpoints. Cox regression analysis was used to estimate hazard ratios (HR) adjusted for donor, recipient, and transplant variables. A total of 3708 HCV-positive and 75,629 HCV-negative kidney transplant recipients were analyzed. RESULTS: Patient survival was negatively affected by HCV-positive serology. Among HCV-positive kidney transplant recipients, a reduced HR for patient death was observed with the use of induction therapy (HR=0.75, 95% CI 0.61-0.90, P=0.003) and with the use of mycophenolate mofetil (HR=0.77, 95% CI 0.64-0.92, P=0.005). CONCLUSIONS: In kidney transplant recipients with HCV-positive serology, the use of antibody induction did not negatively affect patient survival and the use of mycophenolate mofetil as part of maintenance immunosuppression was associated with better patient survival.     

Impact of cytomegalovirus prophylaxis on rejection following orthotopic liver transplantation.

With improved cytomegalovirus (CMV) prophylaxis, CMV disease after liver transplantation has decreased dramatically, and patient and graft survival have improved. We examined the impact of CMV prophylaxis on biopsy proven rejection after orthotopic liver transplantation by analyzing data on 192 liver recipients over 5 years (1994-1999). Risk factors assessed for biopsy proven rejection including donor and recipient age, CMV serostatus; CMV prophylaxis; immunosuppression; bacteremia and blood product use were examined over a 2-year follow-up. Multivariate analysis of risk factors for rejection showed that bacteremia (HR 3.57, 95% CI 1.39-9.36, P=0.008), donor age (HR 1.20, 95% CI 1.06-1.36, per 10 year increase, P=0.004), and use of cyclosporine as initial immunosuppression compared to tacrolimus (HR 1.98, 95% CI 1.27-3.09, P=0.003) were associated with increased risk; ganciclovir prophylaxis for 3 months (HR 0.51, 95% CI 0.33 to 0.79, P=0.003) and recipient age (HR 0.78; 95% CI 0.63-0.96, for each 10 year increase, P=0.03) were associated with decreased risk. We conclude that, the use of CMV prophylaxis with ganciclovir significantly reduces the incidence of biopsy proven rejection in liver transplant recipients.     

Do patient characteristics influence efficacy and renal outcomes in liver transplant patients receiving everolimus?

Data from the 24‐month randomized, multicenter, open‐label H2304 study in 719 de novo liver transplant recipients were analyzed to evaluate the influence of variables potentially affecting immunological or renal response: recipient age, gender, end‐stage disease, hepatitis C virus (HCV) status, and Model for End‐stage Liver Disease score and estimated glomerular filtration rate (eGFR) at randomization (day 30). Treated BPAR was similar between everolimus with reduced tacrolimus (EVR + Reduced TAC) vs. conventional tacrolimus‐based therapy (TAC Control) in all subpopulations, with a trend to lower risk under everolimus with reduced tacrolimus (EVR + Reduced TAC) in patients <60 yrs and HCV‐negative recipients. Risk of graft loss or death was similar in both treatment groups for all subpopulations. The change in eGFR to month 24 showed a benefit for EVR + Reduced TAC vs. TAC Control in all subpopulations other than those with the lowest baseline eGFR (30 to <55 mL/min/1.73m²), with a significant difference in favor of EVR + Reduced TAC for younger recipients (<60 yr), female patients, HCV‐negative patients and those with baseline eGFR of 55 to <70 mL/min/1.73 m². Everolimus with reduced tacrolimus maintains efficacy to at least two yr after liver transplantation even in patients with risk factors for rejection, with particular renal benefits in specific patient subpopulations.     

Everolimus With Reduced Tacrolimus Improves Renal Function in De Novo Liver Transplant Recipients: A Randomized Controlled Trial

In a prospective, multicenter, open‐label study, de novo liver transplant patients were randomized at day 30±5 to (i) everolimus initiation with tacrolimus elimination (TAC Elimination) (ii) everolimus initiation with reduced‐exposure tacrolimus (EVR+Reduced TAC) or (iii) standard‐exposure tacrolimus (TAC Control). Randomization to TAC Elimination was terminated prematurely due to a higher rate of treated biopsy‐proven acute rejection (tBPAR). EVR+Reduced TAC was noninferior to TAC Control for the primary efficacy endpoint (tBPAR, graft loss or death at 12 months posttransplantation): 6.7% versus 9.7% (?3.0%; 95% CI ?8.7, 2.6%; p<0.001 for noninferiority [12% margin]). tBPAR occurred in 2.9% of EVR+Reduced TAC patients versus 7.0% of TAC Controls (p = 0.035). The change in adjusted estimated GFR from randomization to month 12 was superior with EVR+Reduced TAC versus TAC Control (difference 8.50 mL/min/1.73 m², 97.5% CI 3.74, 13.27 mL/min/1.73 m², p<0.001 for superiority). Drug discontinuation for adverse events occurred in 25.7% of EVR+Reduced TAC and 14.1% of TAC Controls (relative risk 1.82, 95% CI 1.25, 2.66). Relative risk of serious infections between the EVR+Reduced TAC group versus TAC Controls was 1.76 (95% CI 1.03, 3.00). Everolimus facilitates early tacrolimus minimization with comparable efficacy and superior renal function, compared to a standard tacrolimus exposure regimen 12 months after liver transplantation.     

Long-term outcomes in liver transplant patients with hepatic C infection receiving tacrolimus or cyclosporine

Choice of calcineurin inhibitor may be a contributing factor to deteriorating patient and graft survival following liver transplantation for hepatitis C virus (HCV). In our multicenter, open-label LIS2T study, de novo liver transplant patients stratified by HCV status were randomized to cyclosporine or tacrolimus. Follow-up data were obtained in an observational study of 95 patients. Mean follow-up was 34 and 37 months, respectively, for cyclosporine-treated (n = 47) and tacrolimus-treated (n = 48) patients. In patients not receiving antiviral therapy, 22 of 31 given cyclosporine (72%) and 24 of 29 given tacrolimus (83%) had biochemical recurrence of HCV. In 68 patients with at least one biopsy, histological evidence of HCV-related hepatitis was present in 27 of 31 (87%) cyclosporine-treated patients and 37 of 37 (100%) tacrolimus-treated patients (P = .02, chi-square test). Three-year actuarial risk of fibrosis stage 2 was 66% with cyclosporine and 90% with tacrolimus; for fibrosis stage 3 or 4 it was 46% and 80%, respectively. Three graft losses were attributed to HCV recurrence in cyclosporine-treated patients and six in tacrolimus-treated patients. Tacrolimus may be associated with increased risk of histological HCV disease recurrence compared to cyclosporine.     

Reduced‐Dose Tacrolimus with Mycophenolate Mofetil vs. Standard‐Dose Tacrolimus in Liver Transplantation: A Randomized Study

We conducted a multicenter randomized study in liver transplantation to compare standard‐dose tacrolimus to reduced‐dose tacrolimus with mycophenolate mofetil to reduce the occurrence of tacrolimus side effects. Two primary outcomes (censored criteria) were monitored during 48 weeks post‐transplantation: occurrence of renal dysfunction or arterial hypertension or diabetes (evaluating benefit) and occurrence of acute graft rejection (evaluating risk). Interim analyses were performed every 40 patients to stop the study in the case of increased risk of graft rejection. One hundred and ninety‐five patients (control: 100; experimental: 95) had been included when the study was stopped. Acute graft rejection occurred in 46 (46%) and 28 (30%) patients in control and experimental groups, respectively (HR = 0.59; 95% CI: [0.37–0.94]; p = 0.024). Renal dysfunction or arterial hypertension or diabetes occurred in 80 (80%) and 61 (64%) patients in control and experimental groups, respectively (HR = 0.68; 95% CI: [0.49–0.95]; p = 0.021). Renal dysfunction occurred in 42 (42%) and 23 (24%) patients in control and experimental groups, respectively (HR = 0.49; 95% CI: [0.29–0.81]; p = 0.004). Leucopoenia (p = 0.001), thrombocytopenia (p = 0.017) and diarrhea (p = 0.002) occurred more frequently in the experimental group. Reduced‐dose tacrolimus with mycophenolate mofetil reduces the occurrence of renal dysfunction and the risk of graft rejection. This immunosuppressive regimen could replace full‐dose tacrolimus in adult liver transplantation.     

Efficacy and safety of tacrolimus compared with ciclosporin‐A in renal transplantation: 7‐year observational results

The European Tacrolimus versus Ciclosporin‐A Microemulsion (CsA‐ME) Renal Transplantation Study demonstrated that tacrolimus decreased acute rejection rates at 6 months. Primary endpoints of this investigator‐initiated, observational 7‐year follow‐up study were acute rejection rates, patient and graft survival rates, and a composite endpoint (BPAR, graft loss, and patient death). We analyzed data from the original intent‐to‐treat population (n = 557; 286 tacrolimus, 271 CsA‐ME). A total of 237 tacrolimus and 208 CsA‐ME patients provided data. At 7 years, Kaplan–Meier estimated rates of patients free from BPAR were 77.1% in the tacrolimus arm and 59.9% in the CsA‐ME arm, graft survival rates amounted to 82.6% and 80.6%, and patient survival rates to 89.9% and 88.1%. Estimated combined endpoint‐free survival rates were 60.2% in the tacrolimus arm and 47.0% in the CsA‐ME arm (P = <0.0001). A higher number of patients from the CsA‐ME arm crossed over to tacrolimus during 7 year follow‐up: 19.7% vs. 7.9% (P = <0.002). More patients in the tacrolimus group stopped steroids and received immunosuppressive monotherapy. Significantly, more CsA‐ME patients received lipid‐lowering medication and experienced cosmetic and cardiovascular adverse events. Tacrolimus‐treated renal transplant recipients had significantly higher combined endpoint‐free survival rates mainly driven by lower acute rejection rates despite less immunosuppressive medication at 7 years.     

Donation after Cardiac Death Liver Transplantation: Predictors of Outcome

We aimed to identify recipient, donor and transplant risk factors associated with graft failure and patient mortality following donation after cardiac death (DCD) liver transplantation. These estimates were derived from Scientific Registry of Transplant Recipients data from all US liver‐only DCD recipients between September 1, 2001 and April 30, 2009 (n = 1567) and Cox regression techniques. Three years post‐DCD liver transplant, 64.9% of recipients were alive with functioning grafts, 13.6% required retransplant and 21.6% died. Significant recipient factors predictive of graft failure included: age ≥ 55 years, male sex, African–American race, HCV positivity, metabolic liver disorder, transplant MELD ≥ 35, hospitalization at transplant and the need for life support at transplant (all, p ≤ 0.05). Donor characteristics included age ≥ 50 years and weight >100 kg (all, p ≤ 0.005). Each hour increase in cold ischemia time (CIT) was associated with 6% higher graft failure rate (HR 1.06, p < 0.001). Donor warm ischemia time ≥ 35 min significantly increased graft failure rates (HR 1.84, p = 0.002). Recipient predictors of mortality were age ≥ 55 years, hospitalization at transplant and retransplantation (all, p ≤ 0.006). Donor weight >100 kg and CIT also increased patient mortality (all, p ≤ 0.035). These findings are useful for transplant surgeons creating DCD liver acceptance protocols.     

Association of hepatitis C with posttransplant diabetes in renal transplant patients on tacrolimus

Posttransplant diabetes mellitus (PTDM) remains a common complication of immunosuppression. Although multiple risk factors have been implicated, none have been clearly identified as predisposing to the increased PTDM frequency observed in patients on tacrolimus. Hepatitis C virus (HCV) has been associated with diabetes and is a significant renal transplant comorbidity. In this study, records of 427 kidney recipients who had no known diabetes before transplantation were retrospectively examined. A multivariate logistic regression model was fit with covariates that had unadjusted relationships with PTDM to examine the independent relationship of HCV and the odds of development of PTDM by 12 mo posttransplant. A potential interaction between HCV and the use of tacrolimus as maintenance therapy on the odds of the development of PTDM was examined. Overall, PTDM occurred more frequently in HCV(+) than HCV(-) patients (39.4% versus 9.8%; P = 0.0005). By multivariate logistic regression, HCV (adjusted odds ratio [OR], 5.58; 95% confidence interval [CI], 2.63 to 11.83; P = 0.0001), weight at transplantation (adjusted OR 1.028; 95% CI, 1.00 to 1.05; P = 0.001), and tacrolimus (adjusted OR, 2.85; 95% CI, 1.01 to 5.28; P = 0.047) were associated with PTDM. A significant interaction (P = 0.0001) was detected between HCV status and tacrolimus use for the odds of PTDM. Among the HCV(+) cohort, PTDM occurred more often in tacrolimus-treated than cyclosporine A-treated patients (57.8% versus 7.7%; P < 0.0001). PTDM rates in HCV(-) patients were similar between the two calcineurin inhibitors (10.0% versus 9.4%; P = 0.521, tacrolimus versus cyclosporine A). In conclusion, HCV is strongly associated with PTDM in renal transplant recipients and appears to account for the increased diabetogenicity observed with tacrolimus.     

De novo noncutaneous malignancies after kidney transplantation are associated with an increased risk of graft failure: results from a time‐dependent analysis on 672 patients

The aim of this study was to evaluate the association between cancer occurrence and risk of graft failure in kidney transplant recipients. From November 1998 to November 2013, 672 adult patients received their first kidney transplant from a deceased donor and had a minimum follow‐up of 6 months. During a median follow‐up of 4.7 years (3523 patient‐years), 47 patients developed a nonmelanoma skin cancer (NMSC) and 40 a noncutaneous malignancy (NCM). A total of 59 graft failures were observed. The failure rate was 6 per 100 patient‐year (pt‐yr) after NCM versus 1.5 per 100 pt‐yr in patients without NCM. In a time‐dependent multivariable model, the occurrence of NCM appeared to be associated with failure (HR = 3.27; 95% CI = 1.44–7.44). The effect of NCM on the cause‐specific graft failure was different (P = 0.002) when considering events due to chronic rejection (HR = 0.55) versus other causes (HR = 15.59). The reduction of the immunosuppression after NCM was not associated with a greater risk of graft failure. In conclusion, our data suggest that post‐transplant NCM may be a strong risk factor for graft failure, particularly for causes other than chronic rejection.     

Effects of the Intensity of Immunosuppressive Therapy on Outcome of Treatment for CMV Disease in Organ Transplant Recipients

An effective host immune response, critical for successful control of Cytomegalovirus (CMV) disease in solid organ transplant recipients, is affected by intensity and type of immunosuppressive therapy. We used information prospectively captured in the VICTOR‐trial to investigate the impact of immunosuppressive therapy on short‐ and long‐term outcomes of CMV treatment in organ transplant recipients. Dual, as compared to triple, immunosuppressive therapy ([odds ratios] OR of 2.55; 95% CI: 1.51–4.60; p = 0.002), lower blood concentrations of calcineurin inhibitors (OR of 5.53; CI: 1.04–29.35; p = 0.045), and longer time since transplantation (OR of 1.70; CI: 1.01–2.87; p = 0.047) all showed better early (Day 21) CMV DNAemia eradication. We observed no effect of the intensity of the immunosuppressive therapy on overall rates of viral eradication or recurrence. The type of calcineurin inhibitor (tacrolimus/cyclosporine) or use of mycophenolate did not affect treatment efficacy, although both tacrolimus and mycophenolate treated patients showed a lower rate of virological recurrence OR 0.51 (95% CI: 0.26–0.98; p = 0.044) and OR 0.45 (95% CI: 0.22–0.93; p = 0.031), respectively. Lower total intensity of immunosuppressive therapy was associated with more effective early, but not overall, CMV DNAemia eradication by valganciclovir/ganciclovir therapy. Both mycophenolate and tacrolimus (rather than cyclosporine) therapy seem to be associated with reduced risk of recurrence.     

The Influence of Induction Therapy on Graft and Patient Survival in Patients with and without Hepatitis C after Liver Transplantation

We used the United Network for Organ Sharing Database to determine the influence of antibody‐based induction therapy on patient and graft survival in orthotopic liver transplant (OLT) recipients with and without hepatitis C (HCV). We identified all initial OLT patients with HCV serology. Patients were divided into four groups: HCV positive without induction (17 362), HCV positive with induction (3479), HCV negative without induction (20 417) and HCV negative with induction (4357). Both HCV positive and negative patients who received induction did better than those who did not. For HCV positive patients, 5‐year patient survival was 70.8% versus 68.7% (p = 0.004) and graft survival was 65.2% versus 62.1% (p < 0.001). For HCV negative patients, 5‐year patient survival was 78.8% versus 76.7% (p < 0.001) and graft survival was 74.0% versus 70.8% (p < 0.001). On multivariate analysis, induction was associated with improved patient (HR = 0.91: p = 0.024) and graft (HR = 0.88: p < 0.001) survival in HCV positive patients and improved patient (HR = 0.87: p = 0.003) and graft survival (HR = 0.87: p < 0.001) in HCV negative patients. The benefit of induction occurred early and largely dissipated when patients with death within a year were censored. The benefit of induction therapy appeared most pronounced in patients with renal insufficiency or on organ‐perfusion support at transplant.     

Pediatric Liver Transplant Recipients Who Undergo Transfer to the Adult Healthcare Service Have Good Long‐Term Outcomes

Liver transplantation has transformed survival for children with liver disease necessitating the transfer of a growing number of patients to the adult healthcare service. The impact of transfer on outcomes remains unclear. The aim of this single‐center study of 137 consecutive pediatric liver transplant recipients was to examine the effect of transfer on patient and graft survival. The median time from transplant to transfer was 10.4 years and the median age of the patients at transfer was 18.6 years. After transfer, there were 5 re‐transplants and 12 deaths in 14 patients. The estimated posttransfer 10‐year patient and graft survival was 89.9% and 86.2%, respectively. Overall, 4 patients demonstrated graft loss as a consequence of chronic rejection. Graft loss was associated with older age at first transplant (p = 0.008). When compared to young adult patients transplanted in the adult center, the transferred patients did not have inferior graft survival from the point of transfer (HR 0.28; 95% CI 0.10–0.77, p = 0.014). This suggests that transfer did not impact significantly on graft longevity. In conclusion, pediatric liver transplant recipients who undergo transfer to the adult service have good long‐term outcomes.