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Background. The long-term use of calcineurin inhibitors (CNIs) after liver transplantation (LT) is associated with nephrotoxicity. Methods. Five-year follow-up data were retrieved from the randomized controlled multicenter SiLVER trial. Standard CNI-based mammalian target of rapamycin-free immunosuppression (group A, n = 264) was compared with a 50% reduction of CNI and introduction of the mammalian target of rapamycin inhibitor Sirolimus (SIR) within 4-6 weeks after LT (group B, n = 261). Results. Median MELD at LT was low with 10 (7-15) (group A) and 11 (8-15) (group B) in the intention-to-treat approach. CNI dose and CNI trough were reduced by 20% and 8% (group A) versus 55% and 56% (group B) at 3 months posttransplantation. Renal function was preserved at 3 months after LT in the SIR arm (estimated glomerular filtration rate 74 [57-95] versus 67 [55-85] mL/min/1.73m2 P = 0.004) but was similarly impaired thereafter compared with group A. The per protocol analysis identified LT recipients in group B with concomitant early CNI minimization and SIR treatment >= year 1 with significantly superior estimated glomerular filtration rate and lowest rate of chronic kidney disease (>= stage 3) from year 1 onwards until study end. Competing risk factors for renal disease (arterial hypertension, fat metabolism disorder, and hyperglycemia) were not associated with worse kidney function. Conclusions. Prevention of CNI nephrotoxicity by SIR-based early CNI minimization protects renal function only short-term after LT in the intention-to-treat analysis of this low MELD cohort. Yet, selected LT recipients compliant with early CNI minimization and SIR maintenance achieved better long-term renal outcomes compared with real-world practice.

BACKGROUND The impact of ethnicity on outcomes after orthotopic liver transplantation (OLT) is unclear. The British Indo-Asian population has a high incidence of liver disease but its contribution to the national deceased donor pool is small. We evaluated access to and outcomes of OLT in Indo-Asians. METHODS We compared 182 Indo-Asians with white patients undergoing OLT. Matching criteria were transplantation year, liver disease, age, sex. Donor and recipient characteristics, postoperative outcomes, including patient and graft survival, OLT era (early, 1987-2001; late, 2002-2011) were compared. Survival was also analyzed by underlying disease-acute liver failure (ALF) and chronic liver failure. RESULTS Indo-Asians had higher diabetes incidence. There were no differences in waiting time for transplantation, despite smaller body size and more uncommon blood groups (B, AB) among Indo-Asians. In the early era, patient survival for Indo-Asians with ALF was worse when compared to whites. In the late era, graft and patient survival at 1, 2, and 5 years were similar between groups. CONCLUSION This study demonstrates that Indo-Asian patients have equal access to OLT and comparable outcomes to whites in the United Kingdom. Survival has improved among Indo-Asian patients; this may be attributable to careful patient selection in case of ALF, though improvement of patient management may have contributed.

Background It is imperative for healthcare providers to examine Western Muslim attitudes on organ donation, because they are reluctant donors. We explored such opinion with the aid of a quantitative survey. Methods Voluntary completion of an anonymous survey was promoted (online and paper sampling). For a population target of approximately 1.6 billion, we targeted a completed sample size of 664 to achieve 5% error margins and 99% confidence intervals (assuming 50% response distribution). Logistic regression analysis was performed to assess independent predictors for organ donation approval. Results In total, 891 global Muslims took the survey with 728 full completions (81.7% completion rate). Paper survey (14% of total) response rate was 62% (124 completed/200 distributed). Western Muslims comprised 76% of participants (n=675) and formed the basis of the analysis. A total of 68.5% of Western Muslims agreed with organ donation, but just 39.3% believed it was compatible with Islam (only 12.7% were registered donors). A total of 1.9% would refuse an organ transplant if required, with 72.4% happy to receive and 25.7% undecided. The main constraints cited by Western Muslims were interpretation of religious scripture (76.5%) and advice from local mosque (70.2%). Predictors for organ donation approval among all global Muslims included younger age, lesser degree of self-rated religiosity, awareness of organ shortages, higher education, and knowing someone with kidney disease/dialysis (all P Conclusion Concern exists among Western Muslims regarding organ donation. Our speculative work should form the basis of larger and more representative assessment of global Muslims to facilitate targeted initiatives to raise awareness.

BACKGROUND Detailed modeling and analysis of renal (dys)function trajectories has not been undertaken in kidney transplant recipients. Although previous studies have assumed linear trajectories, this likely represents an oversimplification. METHODS In this study, a Bayesian smoothing technique was undertaken to create 10,000 Monte Carlo samples for each of 158 patients over a median of 88 months. Specific parameters investigated were the prevalence of nonlinear trajectories, periods of nonprogression, and of rapid progression. RESULTS Forty-five (28%) patients displayed high probability (>80%) for a nonlinear trajectory. Periods of nonprogression were also common, present in 110 (70%) patients. A substantial proportion of patients showed deviation from the classic paradigm of progressive linear loss of graft function with 137 (87%) patients displaying nonlinearity or nonprogression. Only nine (6%) patients demonstrated at least one episode of nonprogression after an episode of progression, that is, once progression occurred, a subsequent period of nonprogression was uncommon. Episodes of nonprogression were less common (P < 0.001) in patients whose grafts subsequently failed, whereas episodes of rapid progression were more common (P = 0.04). CONCLUSION This study highlights the often nonlinear and nonprogressive nature of renal function decline after transplantation. Heightened understanding of the factors influencing these trajectories should help inform patients and clinicians alike.

BACKGROUND Malnutrition is common in patients with end-stage liver disease considered for transplantation, but it is unclear whether this affects the outcome after transplantation. AIM.: To determine whether the severity of malnutrition in liver transplant candidates affects outcome after transplantation. METHODS We did a prospective study of 61 patients with chronic liver disease accepted for transplantation. FINDINGS The Child-Pugh and Model for End-Stage Liver Disease (MELD) score correlated significantly but weakly with the mid-arm circumference (MAC) (rho=-0.34 and -0.31, P=0.015 and 0.025, respectively) but not with hand-grip strength, triceps skin-fold thickness (TSFT), or mid-arm muscle circumference. The Child-Pugh score but not the MELD was significantly associated with intensive therapy unit stay but not eventual outcome; there was a weak but statistically significant correlation between death and MAC (rho=+0.29, P=0.04) and TSFT (rho=+0.25, P=0.02). CONCLUSIONS These findings suggest that nutritional parameters and markers of disease severity do not correlate well with outcomes after transplantation.

There is a relative lack of donor organs for liver transplantation. Ideally, to maximize the utility of those livers that are offered, donor and recipient characteristics should be matched to ensure the best possible posttransplant survival of the recipient.With prospectively collected data on 827 patients receiving a primary liver graft for chronic liver disease, we used a self-organizing map (SOM) (one form of a neural network) to predict outcome after transplantation using both donor and recipient factors. The SOM was then validated using a data set of 2622 patients undergoing transplantation in the United Kingdom at other centers.SOM analysis using 72 inputs and two survival intervals (3 and 12 months) yielded three neurons with either higher or lower probabilities of survival. The model was validated using the independent data set. With 20 patients on the waiting list and 10 sequential donor livers, it was possible to demonstrate that the model could be used to identify which potential recipients were likely to benefit most from each liver offered.With this approach to matching donor livers and recipients, it is possible to inform transplant clinicians about the optimum use of donor livers and thereby effectively make the best use of a scarce resource.

Background. Patients with primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) may have an increased risk of developing colorectal cancer (CRC) after liver transplantation (LT). We evaluated our patients with PSC after LT to identify risk factors for CRC and its impact on survival. Patients and Methods. A total of 152 patients (108 men, 100 with IBD) with PSC who underwent 173 LTs between 1986 and May 2000 were analyzed in three groups: (1) PSC without IBD (n=52); (2) PSC with colectomy (pre-LT and at LT) (n= 17, colectomy pre-LT in 13 and simultaneous colectomy at LT in four); and (3) PSC with IBD and an intact colon (n=83). The following factors were studied: age, gender, liver, and renal biochemistry, international normalized ratio, Child-Pugh stage, operative time, blood use, hospital stay, immunosuppression, risk of CRC, retransplantation rate, and mortality. Results. The incidence of CRC after LT was 5.3% (8/152) compared with 0.6% (7/1,184) in non-PSC cases (P

Liver transplant recipients are at risk of chronic renal disease, principally as a result of nephrotoxicity of the commonly used immunosuppressive agents cyclosporine and tacrolimus. We have investigated the incidence of chronic renal failure and its risk factors in our transplant population, which was treated predominantly with cyclosporine.A single-center retrospective study was done of 883 consecutive adult patients receiving a first liver transplant between 1982 and 1996. Potential risk factors for the development of chronic renal failure were recorded, including serial measurements of cyclosporine therapy and renal function.Severe chronic renal failure (serum creatinine level250 microM/L for at least 6 months) developed in 25 patients, representing 4% of patients surviving 1 year or more. Twelve of these patients developed end-stage renal failure and mortality was 44%. The predominant cause of renal failure was cyclosporine nephrotoxicity. Serum creatinine as early as 3 months after surgery was strongly associated with the eventual development of severe chronic renal failure (P=0.001), and this group could be further subdivided into two groups with differing risk factors. The first group had early (1 year) renal dysfunction, with older age (P=0.03), cytomegalovirus infection (P=0.03), need for perioperative renal replacement therapy (P=0.06), and regrafting (P=0.06) as risk factors for eventual renal failure; the second group had late-onset (1 year) renal dysfunction, with cyclosporine levels at 1 month after surgery (P=0.007) and daily and cumulative cyclosporine dosage at 5 years (P=0.01 for both) as risk factors.With improved survival of liver transplant recipients, chronic renal failure has become an important cause of morbidity and is associated with a high mortality. Many patients at risk of severe chronic renal failure may be identified at an early stage. Treatment regimens that avoid or prevent cyclosporine-induced nephrotoxicity are urgently required for this population.