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BACKGROUND The current Organ Procurement Transplantation Network policy grants Model for End-Stage Liver Disease (MELD) exception points to patients with portopulmonary hypertension (POPH), but potentially important factors, such as severity of liver disease and pulmonary hypertension, are not included in the exception score, and may affect survival. The purpose of this study was to identify significant predictors of waitlist mortality in patients with POPH. METHODS We performed a retrospective cohort study of patients in the Organ Procurement and Transplantation Network database with hemodynamics consistent with POPH (defined as mean pulmonary arterial pressure >25 mm Hg and pulmonary vascular resistance [PVR] ≥240 dynes·s·cm) who were approved for a POPH MELD exception between 2006 and 2014. Using a Cox proportional hazards model, we identified predictors of waitlist mortality (or removal for clinical deterioration). RESULTS One hundred ninety adults were included. Age (hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.00-1.08; P = 0.0499), initial native MELD score (HR, 1.11; 95% CI, 1.05-1.17; P < 0.001), and initial PVR (HR, 1.12 per 100 dynes·s·cm; 95% CI, 1.02-1.23; P = 0.02) were the only significant univariate predictors of waitlist mortality and remained significant predictors in a multivariate model, which had a c-statistic of 0.71. PVR and mean pulmonary arterial pressure were not significant predictors of posttransplant mortality. CONCLUSIONS Both the severity of liver disease and POPH (as assessed by MELD and PVR, respectively) were significantly associated with waitlist, but not posttransplant, mortality in patients with approved MELD exceptions for POPH. Both factors should potentially be included in the POPH MELD exception score to more accurately reflect waitlist mortality risk.

The continued rise in patients suffering from organ failure has raised the need for additional sources for replacement organs to improve the quality of life for these patients. Organ transplantation is the standard of care for end-stage organ disease, and as such, there has been an ever-increasing need worldwide to find suitable grafts for those patients.

We describe four solid-organ transplant recipients with donor-derived West Nile virus (WNV) infection (encephalitis 3, asymptomatic 1) from a common donor residing in a region of increased WNV activity. All four transplant recipients had molecular evidence of WNV infection in their serum and/or cerebrospinal fluid (CSF) by reverse transcription polymerase chain reaction (RT-PCR) testing. Serum from the organ donor was positive for WNV IgM but negative for WNV RNA, whereas his lymph node and spleen tissues tested positive for WNV by RT-PCR. Combination therapy included intravenous immunoglobulin (4 cases), interferon (3 cases), fresh frozen plasma with WNV IgG (2 cases), and ribavirin (1 case). Two of the four transplant recipients survived.Review of the 20 published cases of organ-derived WNV infection found that this infection is associated with a high incidence of neuroinvasive disease (70%) and severe morbidity and mortality (30%). Median time to onset of symptomatic WNV infection was 13 days after transplantation (range 5-37 days). Initial unexplained fever unresponsive to antibiotic therapy followed by rapid onset of neurologic deficits was the most common clinical presentation. Confirmation of infection was made by testing serum and CSF for both WNV RNA by RT-PCR and WNV IgM by serological assays. Treatment usually included supportive care, reduction of immunosuppression, and frequent intravenous immunoglobulin. The often negative results for WNV by current RT-PCR and serological assays and the absence of clinical signs of acute infection in donors contribute to the sporadic occurrence of donor-derived WNV infection. Potential organ donors should be assessed for unexplained fever and neurological symptoms, particularly if they reside in areas of increased WNV activity.

We examined written informed consent forms for living liver donor evaluations to determine whether they incorporated elements required by the Centers for Medicare and Medicaid Services (CMS) and suggested by the Organ Procurement and Transplantation Network (OPTN). We contacted each of the 41 US centers that performed at least 1 living donor liver transplant in 2011; 37 centers reported active living donor evaluation programs. Twenty-six centers shared their consent form for living donor evaluation (response rate = 70%). Each document was double-coded for consent element content. We found that 57% of the centers included the 9 mandated CMS elements. Although the OPTN guidelines are non-binding, 78% of the centers used consent forms that addressed at least two-thirds of the elements recommended by OPTN. Only 17% of the centers provided written offers of an alibi to donors who withdrew from the evaluation. On the basis of our findings, we offer suggestions that may be relevant to ongoing revisions to the OPTN living liver donor consent policy and may help centers to improve the clarity of their written consent forms. Liver Transpl 20:416–424, 2014. © 2014 AASLD.

New onset diabetes after transplantation (NODAT) occurs less frequently in living donor liver transplant (LDLT) recipients than in deceased donor liver transplant (DDLT) recipients. The aim of this study was to compare the incidence and predictive factors for NODAT in LDLT versus DDLT recipients. The Organ Procurement and Transplant Network/United Network for Organ Sharing database was reviewed from 2004 to 2010, and 902 LDLT and 19,582 DDLT nondiabetic recipients were included. The overall incidence of NODAT was 12.2% at 1 year after liver transplantation. At 1, 3, and 5 years after transplant, the incidence of NODAT in LDLT recipients was 7.4, 2.1, and 2.6%, respectively, compared to 12.5, 3.4, and 1.9%, respectively, in DDLT recipients. LDLT recipients have a lower risk of NODAT compared to DDLT recipients (hazard ratio = 0.63 (0.52–0.75),P<0.001). Predictors for NODAT in LDLT recipients were hepatitis C (HCV) and treated acute cellular rejection (ACR). Risk factors in DDLT recipients were recipient male gender, recipient age, body mass index, donor age, donor diabetes, HCV, and treated ACR. LDLT recipients have a lower incidence and fewer risk factors for NODAT compared to DDLT recipients. Early identification of risk factors will assist timely clinical interventions to prevent NODAT complications.

Tacrolimus pharmacokinetics vary due to single nucleotide polymorphisms (SNPs) in metabolizing enzymes and membrane transporters that alter drug elimination. Clinically we observed that Native Americans require lower dosages of tacrolimus to attain trough levels similar to Caucasians. We previously demonstrated that Native Americans have decreased oral clearance of tacrolimus, suggesting that Native Americans may have more variant SNPs and, therefore, altered tacrolimus pharmacokinetic parameters. We conducted 12-hour pharmacokinetic studies on 24 adult Native American kidney transplant recipients on stable doses of tacrolimus for at least 1 month posttransplantation. Twenty-four Caucasian kidney transplant recipients were compared as controls. SNPs encoding the genes for the enzymes (CYP3A4, CYP3A5) and transporters (ABCB1, BCRP, and MRP1) were typed using TaqMan. The mean daily tacrolimus dose in the Native Americans was 0.03 ± 0.02 compared with the Caucasians 0.5 ± 0.3 (mg/kg/d; P = .002), with no significant differences in trough levels, (6.7 ± 3.1 vs 7.4 ± 2.1 ng/dL; P = .4). Many Native Americans, but not Caucasians, demonstrated the 3/*3 - C3435T CC and the *3/*3 -G2677T GG genotype combination previously associated with low tacrolimus dosing. Native Americans required significantly lower tacrolimus doses than Caucasians to achieve similar tacrolimus trough levels, in part due to lower tacrolimus clearance from decreased drug metabolism and excretion.

Background Living-donor liver transplantation (LDLT) has emerged as a viable strategy in an era of organ shortage. However, biliary strictures are a common complication of LDLT, and these strictures frequently require surgical revision after unsuccessful endoscopic therapy. The optimal endoscopic treatment for anastomotic biliary strictures (ABSs) after LDLT is undefined. Objective To determine the outcome of an aggressive endoscopic approach to ABSs after LDLT that uses endoscopic dilation followed by maximal stent placement. Design A retrospective study. Setting A tertiary-care academic medical center. Patients Forty-one patients with a diagnosis of ABS. Interventions Endoscopic retrograde cholangiography with balloon dilation and maximal stenting. Main Outcome Measurements Stricture resolution, stricture recurrence, and complication rates. Results Of 110 LDLTs completed, a biliary stricture developed after transplantation in 41 (37.3%), which included 38 patients with duct-to-duct anastomosis. The median (interquartile range [IQR]) follow-up time is 74.2 (2.5-120.8) months. Among them, 23 (60.5%) were male, and 20 (52.6%) had bile leakage associated with ABSs. The median time (IQR) to the development of an ABS after LDLT was 2.1 (1.2-4.1) months. Endoscopic retrograde cholangiography was attempted as initial therapy in all patients: 32 were managed entirely by endoscopic therapy, and 6 required initial percutaneous transhepatic cholangiography (PTC) to cross the biliary stricture, with endoscopic therapy performed thereafter. A median (IQR) of 4.0 (3.0-5.3) endoscopic interventions and 7.0 (4.0-10.3) stents were required to resolve the stricture. The time from the first intervention to stricture resolution was 5.3 (range 3.8-8.9) months. Biochemical markers including aspartate transaminase (76 vs 39 U/L, P = .001), alanine transaminase (127.5 vs 45.5 U/L, P P P = .017) significantly improved after intervention. Recurrent stricture was observed after initial treatment in 8 (21%) patients. All recurrences were successfully re-treated endoscopically. All patients have been managed without surgical revision or retransplantation, resulting in 100% success by an intention-to-treat analysis. Limitations Retrospective study, small sample size. Conclusions In this series, aggressive endoscopy-based treatment with maximal stent placement strategy allows 100% resolution of all duct-to-duct ABSs after LDLT without the need for surgical intervention or retransplantation.

Few studies address the potential for donation after brain death (DBD) in the limited population of patients with ongoing mechanical circulatory support (MCS). A case study was conducted reviewing available records of both donor and recipient, and available literature. The donor was a young female with an acute myocardial infarction precipitating emergent off-pump 2-vessel bypass graft complicated by profound cardiogenic shock refractory to inotropes and intra-aortic balloon pump. A heparin drip was started following percutaneous placement of a left ventricular-assist device (TandemHeart?) which improved her hemodynamics to stabilize for transfer. She ultimately required surgical placement of biventricular assist device (CentraMag?) to normalize hemodynamics. Two days post-operatively, she developed a cerebellar hemorrhage and was declared brain dead. Pre-donation blood chemistry showed adequate end-organ function. Both kidneys were placed locally. The liver was rejected for two regional status 1 patients and by all other local centers. We accepted the liver for a patient with polycystic liver disease with a MELD exception score of 20. The recipient is now 4 years post-transplant with excellent graft function. Extending donor criteria to include MCS patients can result in successful transplantation and should be considered in selected circumstances once satisfactory donor end-organ function is established.

BackgroundThe probability of liver transplant and death on the waiting list in the United States varies greatly by donation service area (DSA) due to geographic differences in availability of organs and allocation of priority points, making it difficult for providers to predict likely outcomes after listing. We aimed to develop an online calculator to report outcomes by region and patient characteristics.MethodsUsing the Scientific Registry of Transplant Recipients database, we included all prevalent US adults aged 18 years or older waitlisted for liver transplant, examined on 24 days at least 30 days apart over a 2-year period. Outcomes were determined at intervals of 30 to 365 days. Outcomes are reported by transplant program, DSA, region, and the nation for comparison, and can be shown by allocation or by laboratory model for end-stage liver disease (MELD) score (6-14, 15-24, 25-29, 30-34, 35-40), age, and blood type.ResultsOutcomes varied greatly by DSA; for candidates with allocation MELD 25-29, the 25th and 75th percentiles of liver transplant probability were 30% and 67%, respectively, at 90 days. Corresponding percentiles for death or becoming too sick to undergo transplant were 5% and 9%. Outcomes also varied greatly for candidates with and without MELD exception points.ConclusionsThe waitlist outcome calculator highlights ongoing disparities in access to liver transplant and may assist providers in understanding and counseling their patients about likely outcomes on the waiting list.

Organ shortage remains a major barrier to transplantation. While many efforts have focused on educating the general population regarding donation, few studies have examined knowledge regarding donation and donor registration rates among waitlisted candidates. We aimed to determine waitlisted patients’ willingness to donate, elucidate attitudes surrounding organ allocation, and identify barriers to donation. A cross-sectional survey was distributed to assess demographics, knowledge regarding organ donation, and attitudes regarding the allocation process. Responses from 225 of 579 (39%) waitlisted patients were collected. 71 respondents (32%) were registered donors, while 64 patients (28%) noted no interest in participating in donation. 19% of respondents felt their medical treatment would change by being a donor, while 86 patients (38%) felt their condition precluded them from donation. 40 patients (18%) felt they should be prioritized on the waitlist if they agreed to donate. A minority of patients (28%) reported discussion of organ donation with their physician. Waitlisted candidates constitute a population of willing, though often unregistered, organ donors. Moreover, many endorse misconceptions regarding the allocation process and their donation eligibility. In a population for which transplantation is not always possible, education is needed regarding organ donation among waitlisted patients, as this may enhance donation rates. This article is protected by copyright. All rights reserved.

Background Cardiovascular disease is the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). In fact, death from cardiovascular disease is the number one cause of graft loss in kidney transplant (KTx) patients. Compared to patients on dialysis, CKD patients with KTx have increased quality and length of life. It is not known however whether outcomes of coronary artery bypass graft (CABG) surgery differ between CKD patients with KTx or on dialysis. Methods This was a retrospective cohort study comparing CKD patients with KTx or on dialysis undergoing CABG surgery included in the Nationwide Inpatient Sample from 2002-2011. Logistic and linear regression models were used to estimate the adjusted associations of KTx on all-cause in-hospital mortality, length of stay, cost of hospitalization, and rate of complications in CABG surgery. Results CKD patients with KTx had decreased all-cause in-hospital mortality (2.68% vs. 5.86%, Odds Ratio (OR) = 0.56, 95% Confidence Interval (CI) = 0.32– 0.99, P = 0.046), length of stay (Beta = -2.96, 95% CI = -3.67 – -2.46, P

Background Delirium is increasingly recognized as a common and important postoperative complication that significantly hinders surgical recovery. However, there is a paucity of data examining the incidence and impact of delirium after liver transplantation. Methods Retrospective case series in a tertiary care center examining all ( n = 144) adult patients who underwent liver transplantation during a 6-y period. Results Delirium occurred in 25% of the patients with an average duration of 4.56 d. Patients who developed delirium were older ( P = 0.007), had higher preoperative model for end-stage liver disease score ( P = 0.019) and longer pretransplant hospital length of stay (LOS; P = 0.003). Patients with delirium were also more likely to have alcohol ingestion as an etiology of the liver failure ( P = 0.033). Delirious patients had a trend toward increased ventilator days ( P = 0.235) and significantly longer postoperative hospital ( P = 0.001) and intensive care unit LOS ( P = 0.001). Delirium was also associated with an increased frequency of hospital acquired infections including urinary tract infections ( P = 0.005) and pneumonias ( P = 0.001). Conclusions Delirium is a common occurrence among liver transplant patients associated with increased complications and LOSs. Further prospective studies are needed to determine the specific risk factors in this complex population and to determine if delirium has an impact on long-term outcomes.

Seizure disorder is a common neurologic complication of kidney transplantation and often presents as a complex management challenge. Little is known about the risks mutually conferred by the 2 clinical entities and the effects of such risks on clinical outcomes. Using the National Inpatient Sample, our goal was to examine the effects of kidney transplantation and seizure disorder on mortality, hospitalization statistics, clinical complications, and cost of care. A history of kidney transplantation was shown to negatively affect the care of seizure disorder, and a history of seizure disorder also negatively affected the clinical outcomes of kidney transplantation. Our findings are important for initiating discussions and prompting future studies to further examine disease-specific risks of kidney transplantation.

Liver transplant recipients have a high risk of infectious complications, compared with recipients of other solid organs, despite the improvement in surgical techniques, shortening of operative times, and the development of novel anti-infective agents in the last decade. A careful examination of risk factors, diligent surveillance for early signs of infection, and prompt intervention are necessary to minimize serious infectious complications, which often contribute to graft loss and death in this population. Future strategies to develop diagnostic assays that are rapid, cost-effective, standardized, and easily performed will improve our abilities to prevent donor-transmitted infections. Ability to assess the immune competence of the recipients and to optimally prescribe appropriate antimicrobial prophylaxis will allow us to prevent infection. Areas such as liver transplant in HIV coinfection and the prevention of recurrence of viral hepatitides after transplantation have made some progress but require further research before the establishment of accepted therapeutic strategies.

BK virus (BKV) and John Cunningham virus (JCV) are nonenveloped icosahedral DNA viruses, members of the family Polyomaviridae. Studies have estimated that the adult population worldwide is approximately 80% seropositive for BKV and approximately 50%–70% seropositive for JCV, with JCV seropositivity increasing with age [1–3]. Primary infection normally occurs during childhood, with the viruses then establishing latency/persistence in different organs, including the kidney [4, 5]. BKV and JCV undergo periodic reactivation and replication, and may cause disease in immunosuppressed hosts [6–10]. It is not known exactly which factors control the balance between latency and reactivation of BKV and JCV, but available data suggest that the cellular immune response exerts important control over these viruses [6, 11–14]. BKV is known to cause diseases of the genitourinary tract, such as hemorrhagic cystitis in bone marrow and hematopoietic stem cell transplant recipients and ureteric stenosis in renal transplant patients. However, the virus is most frequently implicated with the development of polyomavirus-associated nephropathy (PVAN) in kidney transplant patients [6, 9, 15, 16]. Reduced host immunity seems to play an important role, as studies indicate that lowering of the level of immunosuppression is associated with a decrease in BKV viral load and reduction of allograft inflammation in kidney transplant patients [6, 8, 15, 16]. Progressive multifocal leukoencephalopathy is a disease of the central nervous system, characterized by multiple foci of demyelination caused by lytic JCV infection of oligodendrocytes [7, 10, 17, 18]. Progressive multifocal leukoencephalopathy has been reported among heart, kidney, and liver transplant recipients, but its true incidence in these patient groups is not known [6, 19–21]. In addition, JCV has also been associated with some cases of PVAN in kidney transplant recipients [22–24]. Data suggest that JCV-associated PVAN may be characterized by sparse cytopathic changes but significant inflammation and fibrosis in kidney transplant patients [24]. However, the relationship between JCV reactivation and renal dysfunction is not clear, as systematic monitoring of JCV infection is not performed in kidney and nonkidney transplant patients. A high incidence of renal dysfunction has been reported in nonrenal transplant recipients [25, 26]. This renal disease has been attributed to the cumulative toxicity of calcineurin inhibitors, but many of these patients are not monitored for polyomavirus reactivation, so it is possible that polyomaviruses are more commonly associated with this clinical syndrome than currently appreciated. There is a need, therefore, for prospective studies to examine the role of BKV and JCV in renal dysfunction among nonrenal organ transplant patients. In addition, some questions remain concerning the clinical management of BKV and JCV following organ transplantation, such as the dynamics of reactivation of individual viruses in different organ transplant groups and the advisability of viral monitoring. In this prospective study, we examined BKV and JCV urinary shedding and their relationship with creatinine clearance (CrCl) in outpatient liver and kidney transplant recipients to determine whether the patterns of viral reactivation were similar in the 2 patient groups and if viral shedding was associated with renal dysfunction in liver transplant recipients.

Ampullary and proximal pancreatic duct strictures are well known to result in recurrent episodes of pancreatitis in the native pancreas, which when benign in origin can often be treated with sphincteroplasty (open or endoscopic) and stenting in the native pancreas. However, recurrent episodes of pancreatitis in a transplanted pancreas allograft can have multiple potential etiologies, and if the diagnosis of pancreatic duct stricture is made, treatment with preservation of the pancreatic allograft can be challenging. This is the first case report to describe the open sphincteroplasty of a short benign ampullary stricture in a transplant pancreas allograft.

Background. Our aim was to study the impact of clinical acute rejection (CR) and subclinical rejection (SR) on outcomes in kidney transplant recipients treated with rapid steroid withdrawal (RSW). Methods. All patients who received a living or deceased donor kidney transplant and were treated with RSW were included. The primary outcome was death-censored graft survival. Biopsies with Banff borderline changes were included with the rejection groups. Results. 457 kidney transplant recipients treated with RSW were included; 46 (10%) experienced SR, and 36 (7.8%) had CR. Mean HLA mismatch was significantly higher in the CR group. The Banff grade of rejection was higher in the CR group. There was a larger proportion of patients in both rejection groups with the combination of IFTA and persistent inflammation on the follow-up protocol biopsy done at 1 year. The estimated 5-year death-censored graft survival was 81% in SR, 78% in CR, and 97% in the control group ( ). Significant differences were observed in allograft survival between the CR and control group (HR 9.06, 95% CI 3.39–24.2) and between the SR and control group (HR 4.22, 95% CI 1.30–13.7). Conclusion. Both SR and CR are associated with an inferior graft survival in recipients on RSW.

Background and objectives: Approximately two-thirds of kidney transplant recipients with no previous history of diabetes experience inpatient hyperglycemia immediately after kidney transplant surgery; whether inpatient hyperglycemia predicts future new onset diabetes after transplant (NODAT) is not established. Design, setting, participants, & measurements: A retrospective study was conducted to determine the risk conferred by inpatient hyperglycemia on development of NODAT within 1 year posttransplant. All adult nondiabetic kidney transplant recipients between June 1999 and January 2008 were included. Posttransplant inpatient hyperglycemia was defined as any bedside capillary blood glucose ≥ 200 mg/dl or insulin therapy during hospitalization. NODAT was defined as HbA1C ≥ 6.5%, fasting venous serum glucose ≥ 126 mg/dl, or prescribed diet or medical therapy for diabetes mellitus. Results: The study cohort included 377 patients. NODAT developed in 1 (4%) of the 28 patients without inpatient hyperglycemia, 4 (18%) of the 22 patients with inpatient hyperglycemia but not treated with insulin, and in 98 (30%) of the 327 of the patients who were diagnosed with inpatient hyperglycemia and were treated with insulin. In adjusted analyses, requirement of insulin therapy during hospitalization posttransplant was associated with a 4-fold increase in NODAT (relative risk 4.01; confidence interval, 1.49 to 10.7; P = 0.006). Conclusion: Development of inpatient hyperglycemia after kidney transplantation in nondiabetic patients significantly increased the risk of NODAT. Additionally, we observed a significantly increased risk of cardiovascular events in patients who developed NODAT.

Potential donors with congenital renal anomalies but normal renal function are often overlooked because of a possible increase in technical difficulty and complications associated with the surgery. However, as the waiting list for a deceased donor kidney transplant continues to grow, it is important to consider these kidneys for potential transplant. This paper describes the procurement of a crossed fused ectopic kidney, and subsequent parenchymal transection prior to transplantation as part of a combined simultaneous kidney pancreas transplant. The transplant was uncomplicated, and the graft had immediate function. The patient is now two years from transplant with excellent function.

New-onset diabetes mellitus, which occurs after kidney transplant and type 2 diabetes mellitus (T2DM), shares common risk factors and antecedents in impaired insulin secretion and action. Several genetic polymorphisms have been shown to be associated with T2DM. We hypothesized that transplant recipients who carry risk alleles for T2DM are "tipped over" to develop diabetes mellitus in the posttransplant milieu.We investigated the association of genetic and traditional risk factors present before transplantation and the development of new-onset diabetes mellitus after kidney transplantation (NODAT). Markers in 8 known T2DM-linked genes were genotyped using either the iPLEX assay or allelic discrimination (AD)-PCR in the study cohort testing for association with NODAT. We used univariate and multivariate logistic regression models for the association of pretransplant nongenetic and genetic variables with the development of NODAT.The study cohort included 91 kidney transplant recipients with at least 1 year posttransplant follow-up, including 22 who developed NODAT. We observed that increased age, family history of T2DM, pretransplant obesity, and triglyceridemia were associated with NODAT development. In addition, we observed positive trends, although statistically not significant, for association between T2DM-associated genes and NODAT.These findings demonstrated an increased NODAT risk among patient with a positive family history for T2DM, which, in conjunction with the observed positive predictive trends of known T2DM-associated genetic polymorphisms with NODAT, was suggestive of a genetic predisposition to NODAT.

Our aim was to assess long-term survival in patients transplanted for HCV-related end-stage liver disease (ESLD) and evaluate potentially modifiable predictors of survival. We performed a retrospective analysis of adult liver transplants (LT) at our institution for HCV-related ESLD since the program's inception. Pertinent demographic, clinical, and biochemical information was retrieved from electronic medical records and histological data from 990 per-protocol liver biopsies were collected. Three hundred eighty LT were performed at our institution during the study period, 206 patients were transplanted for HCV-related ESLD; 6 died within 30 days of transplantation and were not included. The remaining 200 recipients (DDLT 168 LDLT 32) constituted the evaluable population. The demographics were as follows: 150 males, median age 53 years; median donor age 39 years; hepatocellular carcinoma (HCC) in 26%. Overall 1-, 5-, and 7-year survival: 95%, 81%, and 79%; median survival 43 months, mortality 15%. Significant HCV recurrence (HAI ≥6 and/or fibrosis ≥2) was present in 49%, “early recurrence” (within 1 year of LT) in 30.5% and biopsy-proven acute rejection was present in 27%. Factors with a significant negative impact on patient survival included: fibrosis stage ≥2 at 12-month biopsy, advanced donor age, history of HCC and early acute rejection. Survival was similar regardless of the donor type (DDLT vs. LDLT). Early and aggressive HCV recurrence has a very heavy toll on patient survival. Prompt recognition and treatment of “rapid fibrosers” may impart benefit. As has been described before, avoidance of rejection and selection of young donors for HCV-positive recipients will also improve survival in this population. On the basis of our findings, LDLT is a good option for HCV-positive recipients. Liver Transpl 15:1872–1881, 2009. © 2009 AASLD.

The American Society of Transplant Surgeons (ASTS) champions efforts to increase organ donation. Controlled donation after cardiac death (DCD) offers the family and the patient with a hopeless prognosis the option to donate when brain death criteria will not be met. Although DCD is increasing, this endeavor is still in the midst of development. DCD protocols, recovery techniques and organ acceptance criteria vary among organ procurement organizations and transplant centers. Growing enthusiasm for DCD has been tempered by the decreased yield of transplantable organs and less favorable posttransplant outcomes compared with donation after brain death. Logistics and ethics relevant to DCD engender discussion and debate among lay and medical communities. Regulatory oversight of the mandate to increase DCD and a recent lawsuit involving professional behavior during an attempted DCD have fueled scrutiny of this activity. Within this setting, the ASTS Council sought best-practice guidelines for controlled DCD organ donation and transplantation. The proposed guidelines are evidence based when possible. They cover many aspects of DCD kidney, liver and pancreas transplantation, including donor characteristics, consent, withdrawal of ventilatory support, operative technique, ischemia times, machine perfusion, recipient considerations and biliary issues. DCD organ transplantation involves unique challenges that these recommendations seek to address.

Sclerosing peritonitis describes the development of a peel or rind of fibrosis that spreads over the peritoneal surface and can lead to recalcitrant ascites, bowel obstruction, and sepsis. It is well described as a complication of peritoneal dialysis, especially with episodes of bacterial peritonitis. It is also a complication of end-stage liver disease with ascites and liver transplantation. This article describes 3 cases of sclerosing peritonitis present at the time of liver transplantation or soon after. All 3 patients had massive refractory ascites with episodes of spontaneous bacterial peritonitis prior to transplantation. Two patients had evidence of a fibrous peel at the time of transplantation. Postoperatively, all 3 patients continued to have refractory ascites and episodes of peritonitis, along with partial small bowel obstructions, abdominal pain, and malnutrition. Two patients also had constriction of the graft, including biliary obstruction and inferior vena cava and outflow obstruction, which has not been previously described. All 3 patients eventually died from complications related to the sclerosing peritonitis.

Background: Recent studies have documented good patient and graft outcomes and a low risk of acute rejection with steroid-avoidance immunosuppression in kidney-transplant recipients, but the risk of progressive graft fibrosis is not well studied. Methods: All adult primary kidney transplant or combined kidney and pancreas transplant recipients on steroid avoidance immunosuppression were eligible for study. All recipients received induction with antithymocyte globulin or basiliximab. Corticosteroids were stopped after day 4 post-transplantation. Patients were maintained with tacrolimus and mycophenolate mofetil. Protocol biopsies were done at reperfusion and at one, four, and 12 months after transplantation. Results: Eighty one-yr protocol biopsies with adequate specimens were obtained from 132 kidney or kidney–pancreas transplant recipients. Fifteen (19%) of the biopsies showed moderate to severe graft interstitial fibrosis (GIF) (Banff ci score ≥2). Recipients with GIF were older, had lower body mass index, greater human lymphocyte antigen (HLA) mismatch, older donors, serum creatinine ≥1.6 mg/dL at one month, a Banff ci score >0 on one-month biopsy, BK nephropathy, and interstitial cellular infiltrates on the one-yr biopsy. In the unadjusted logistic regression analysis, BK nephropathy, serum creatinine ≥1.6 mg/dL at one month, recipient age, Banff ci score >0 on one-month biopsy, and donor age were the only variables associated with a higher risk of GIF on the one-year biopsy. In the multivariate logistic regression model adjusted for these variables, BK nephropathy, serum creatinine ≥1.6 mg/dL at one month after transplantation, and recipient age were independently associated with the risk of GIF on the one-year biopsy. Conclusion: In this small study of primary kidney or combined kidney–pancreas transplant recipients on steroid-avoidance immunosuppression, we found that 19% had GIF on a one-year protocol biopsy. BK nephropathy, serum creatinine ≥1.6 mg/dL one month after transplantation, and recipient age correlated with an increased risk for GIF on the one-yr biopsy.

Kluyvera species are opportunistic, gram-negative bacilli in the family Enterobacteriaceae. Ordinarily occurring as a commensal, Kluyvera have been reported to cause serious infections in immunosuppressed and immunocompetent hosts, causing diarrhea, urinary infections, peritonitis, and cholecystitis. We report Kluyvera infections in 2 solid organ transplant recipients. An 18-year-old female with alpha-1 antitrypsin deficiency underwent living donor liver transplantation and presented 6 months later with a liver abscess. The abscess aspirate grew mixed organisms including Kluyvera cryocrescens. A 22-year-old female with renal failure secondary to focal segmental glomerulosclerosis underwent a deceased donor kidney transplant and presented 3 months later with pyelonephritis; the urine culture grew Kluyvera ascorbata. Both patients improved only when their antibiotic coverage was broadened to include Kluyvera. The isolation of Kluyvera as a pathogen in transplant patients emphasizes that this commensal organism may be virulent in this patient population.

Coccidioidomycosis is a fungal infection caused by Coccidioides species endemic to the southwestern United States, where it poses unique challenges for transplant recipients. Donor-derived coccidioidomycosis has been documented, but its risk of transmission is not known. We prospectively screened 568 healthy persons requesting evaluation for possible liver or kidney donation. Twelve (2.1%) of the 568 donor candidates were seropositive (11 initially and 1 with seroconversion and symptomatic illness within 1 week after negative screening). Three of these 12 patients proceeded to kidney donation, and a fourth patient proceeded to liver donation. None of the 4 transplant recipients received special coccidioidal prophylaxis, although all were administered fluconazole according to standard antifungal prophylaxis protocols. At follow-up (7–54 months), no coccidioidomycosis was identified in any recipient. The prevalence of coccidioidal antibodies was low among potential organ donor candidates, but the risk of donor-derived coccidioidomycosis remains unknown and further study is warranted.

Keywords: ethics and public policy; liver transplantation/hepatology; organ allocation; United Network for Organ Sharing (UNOS)

We read with interest the Commentary of Mehrotra, et al., on modeling the organ allocation system (1), and wish to reply to critiques of the process and the methods used by the Organ Procurement and Transplantation Network (OPTN) to establish more equitable liver allocation. The Department of Health and Human Services (DHHS) and Health Resources and Services Administration (HRSA) have long since given a mandate, in the published Final Rule, to minimize the effect of geography on access to transplantation for all candidates. The OPTN Board has instructed the Liver Committee to investigate redistricting (2, 3) and other approaches for reducing an unacceptable level of geographic disparity. While the liver committee’s concept document primarily focused on redistricting, other publicly presented approaches have included broader sharing within the existing regions, and circular proximity distribution. Mehrotra et al. suggest statewide sharing as another alternative. The Liver Simulated Allocation Model (LSAM) certainly can be used to test sharing within any boundaries, optimized or not, but statewide sharing cannot reduce geographic disparity because there are enormous differences between states’ listing and eligible death rates. Furthermore, because donor service area (DSA) boundaries do not respect state borders, statewide sharing would disrupt organ procurement organization / DSA relationships. Of the approaches that the committee examined, optimized redistricting would yield the best improvement in geographic equity. Deceased donor livers have been allocated according to model for end stage liver disease (MELD) score since 2002. Variation in transplant MELD across the country is not a desirable feature of allocation, but rather a measure of the extent to which ad hoc geographic boundaries have prevented organs from reaching the candidates who would derive the greatest benefit. Despite intimations to the contrary, prioritizing candidates by MELD score also prioritizes the candidates with highest survival benefit from transplantation (4). While ethical arguments about how candidates should be prioritized are important, changing the ordering of the waiting list within each geographic unit would not alter the calculus of geographic disparity. Maintaining geographic divisions in which supply and demand are profoundly imbalanced by disparate listing and eligible death rates (5) will prevent organs from reaching the most appropriate recipients, no matter which prioritization order is chosen. We agree that redistricting should be dynamic, updating the districts whenever geographic disparities become so large as to be visibly unfair. Clearly, current disparities merit changes to the allocation map. Reassuringly, the sizable benefits of redistricting plans are stable from year to year; for example, districts optimized for 2006 data were still dramatically more equitable than the existing regions in a simulation using 2010 data (3). Mehrotra et al. cite technical concerns about LSAM. Transplant policymakers have used the SAMs for many years to predict outcomes of allocation changes, and the SRTR has made major improvements in LSAM to support current liver committee efforts. For example, outcomes after the recent Share-35 change were similar to LSAM's projections (6). Still, we agree that LSAM does not and likely cannot predict behavior changes. However, in evaluating redistricting, this biases the simulation against accepting long-distance offers, and therefore the projected reductions in disparity from redistricting are very likely underestimates. Moreover, LSAM plays no role in designing the redistricted maps; it only evaluates the impact of these optimized maps in a granular simulation. The optimal districts are solutions to integer programs, independent of LSAM, that harmonize supply (deceased donors) and demand (waiting candidates whose MELD exceeds a threshold) in each area. Mehrotra et al. argue for many additional sensitivity analyses and robust optimization techniques. While such studies would surely be welcomed from any contributor, they would also surely take time and have small marginal benefit. In the nearly 5 years since the OPTN effort for geographic equity began, hundreds of liver transplant candidates have died waiting for an organ that would have arrived in time under any of the redistricting plans proposed (2). Those candidates could not wait for perfect answers, and more candidates will meet needless deaths as long as the perfect remains the mortal enemy of the good.

In June of 2013, the Organ Procurement and Transplantation Network (OPTN) implemented regional sharing for Model for End-Stage Liver Disease (MELD)/Pediatric End-Stage Liver Disease (PELD) candidates with scores reaching 35 and above ("Share 35"). The goal of this distribution change was to increase access to lifesaving transplants for the sickest candidates with chronic liver disease and to reduce the waiting-list mortality for this medically urgent group of patients. To assess the impact of this change, we compared results before and after policy implementation at 2 years. Overall, there were more liver transplants performed under Share 35 and a greater percentage of MELD/PELD 35+ candidates underwent transplantation; waiting-list mortality rates in this group were also significantly lower in the post-policy period. Overall adjusted waiting-list mortality was decreased slightly, with no significant changes in mortality by age group or ethnicity. Posttransplant graft and patient survival was unchanged overall and was unchanged for the MELD/PELD 35+ recipients. In conclusion, these data demonstrate that the Share 35 policy achieved its goal of increasing access to transplants for these medically urgent patients without reducing access to liver transplants for pediatric and minority candidates. Although the variance in the median MELD at transplant as well as the variance in transport distance increased, there was a decrease in overall liver discard rates and no change in overall cold ischemia times following broader sharing of these organs. The OPTN will continue to monitor this policy, particularly for longer-term posttransplant survival outcomes.

In June 2013, a change to the liver waitlist priority algorithm was implemented. Under Share 35, regional candidates with MELD ≥ 35 receive higher priority than local candidates with MELD 35. We compared liver distribution and mortality in the first 12 months of Share 35 to an equivalent time period before. Under Share 35, new listings with MELD ≥ 35 increased slightly from 752 (9.2% of listings) to 820 (9.7%, p = 0.3), but the proportion of deceased-donor liver transplants (DDLTs) allocated to recipients with MELD ≥ 35 increased from 23.1% to 30.1% (p 0.001). The proportion of regional shares increased from 18.9% to 30.4% (p 0.001). Sharing of exports was less clustered among a handful of centers (Gini coefficient decreased from 0.49 to 0.34), but there was no evidence of change in CIT (p = 0.8). Total adult DDLT volume increased from 4133 to 4369, and adjusted odds of discard decreased by 14% (p = 0.03). Waitlist mortality decreased by 30% among patients with baseline MELD 30 (SHR = 0.70, p 0.001) with no change for patients with lower baseline MELD (p = 0.9). Posttransplant length-of-stay (p = 0.2) and posttransplant mortality (p = 0.9) remained unchanged. In the first 12 months, Share 35 was associated with more transplants, fewer discards, and lower waitlist mortality, but not at the expense of CIT or early posttransplant outcomes.

The liver organ allocation policy of the United Network for Organ Sharing (UNOS) is based on the model for end-stage liver disease (MELD). The policy provides additional priority for candidates with hepatocellular carcinoma (HCC) who are awaiting deceased donor liver transplantation (DDLT). However, this priority was reduced on February 27, 2003 to a MELD of 20 for stage T1 and of 24 for stage T2 HCC. The aim of this study was to determine the impact of reduced priority on HCC candidate survival while on the waiting list. The UNOS database was reviewed for all HCC candidates listed after February 27, 2002, The HCC candidates were grouped into two time periods: MELD 1 (listed between February 27, 2002, and February 26, 2003) and MELD 2 (listed between February 27, 2003 and February 26, 2004). For the two time periods, the national DDLT incidence rates for HCC patients were 1.44 versus 1.53 DDLT per person-year (p = NS) and the waiting times were similar for the two periods (138.0 +/- 196.8 vs. 129.0 +/- 133.8 days; p = NS). Furthermore, the 3-, 6- and 12-month candidate, patient survival and dropout rates were also similar nationally. Regional differences in rates of DDLT for HCC were observed during both MELD periods. Consequently, the reduced MELD score for stage T1 and T2 HCC candidates awaiting DDLT has not had an impact nationally either on their survival on the waiting list or on their ability to obtain a liver transplant within a reasonable time frame. However, regional variations point to the need for reform in how organs are allocated for HCC at the regional level.

Immunosuppression with rapid discontinuation of corticosteroids, usually with induction therapy, is safe in kidney transplant recipients. In 89 patients, we induced immunosuppression with basiliximab or rabbit antithymocyte globulin (17 and 72 patients, respectively). Selection criteria for basiliximab were age (>or=65 years), history (malignancy; chronic infection), and type 1 diabetes mellitus (eligible for pancreas transplant). Steroids were administered through posttransplantation day 4 (five doses); maintenance immunosuppression was with tacrolimus and mycophenolate mofetil. At last follow-up (average, 286 days), most patients were steroid-free (antithymocyte globulin, 90%; basiliximab, 88%). Protocol biopsies were performed at 1, 4, and 12 months posttransplantation. The overall risk of biopsy-proven acute rejection was 12%. At 6 months posttransplantation, acute rejection-free survival was 93% for antithymocyte globulin, 65% for basiliximab (P

Model for Endstage Liver Disease (MELD) score has been used to allocate organs since February 2002. This policy allocates organs to candidates with regard to severity of their underlying liver disease except in the case of hepatocellular carcinoma (HCC) patients. The purpose of this study was to determine the impact of MELD on waiting times, dropout rates, and transplantation rates in all patients awaiting liver transplantation at our center. The records of all patients listed for liver transplantation between May 28, 1999, and February 27, 2004, at the Mayo Clinic, Scottsdale, Arizona, were reviewed. Candidates were grouped by two time periods as pre-MELD or post-MELD based on date of MELD implementation (February 27, 2002). The incidence of deceased donor liver transplantation (DDLT), waiting time to DDLT, dropout rate from the waiting list because of clinical deterioration or death, and survival while waiting for or after DDLT were determined for each group. Three hundred fifty-one patients were listed for liver transplantation (195 pre-MELD, 156 post-MELD) during the study period. HCC patients had an improved rate of transplantation after MELD (pre-MELD, 1.39 persons per year; post-MELD, 3.48 persons per year). In all groups, with the exception of hepatitis C virus, the transplantation rates were the same for both categories. The hepatitis C virus group also had improved transplantation rates in the post-MELD period. HCC candidates under the new allocation policy have an increased incidence of DDLT in our institution. However, this has not disadvantaged patients with non-HCC diagnoses. Thus, the new MELD-based allocation policy has benefited all candidates by allowing more timely transplants.

The question of possible earlier and more aggressive recurrence of hepatitis C virus (HCV) infection after living donor liver transplantation (LDLT) compared to deceased donor liver transplantation (DDLT) remains unanswered. To address this issue we retrospectively reviewed virological, histological, and clinical data in 67 patients (52 DDLT and 15 LDLT) who underwent liver transplant for their HCV-related cirrhosis since April 2001. Our data indicate that there is no statistical difference between LDLT and DDLT groups in mean age, Child-Turcotte-Pugh score, model for end-stage liver disease score, and gender distribution. The mean follow-up was 749 +/- 371 days in LDLT and 692 +/- 347 days in DDLT. The predominant genotype in the LDLT and DDLT are genotype 1 (LDLT, 91%; DDLT, 70%). All patients with histologically confirmed recurrent HCV had detectable HCV-RNA in serum. The histological recurrence rate of hepatitis C was 58% at 4 months, 90% at 1 year, and 100% at 2 years in LDLT patients vs. 71% at 4 months, 94% at 1 year, and 95% at 2 years in DDLT patients (not significant) Comparison of the activity of inflammation and fibrosis score at all time points failed to show a statistical difference. Kaplan-Meier survival analysis showed similar patient and graft survival rates between the 2 groups. Our data indicate that histological recurrence of HCV is an early event and virtually universal 2 years' posttransplantation, regardless of modality of donor procurement.

The aim of this study was to define liver shear stiffness by magnetic resonance elastography (MRE) that distinguishes normal from abnormal liver biopsy, especially when steatosis ≥20%, among potential live liver donors. Baseline clinical, laboratory, imaging, MRE, and liver biopsy results were recorded. Using MRE, hepatic shear stiffness in kilopascals (kPa) was measured and compared to liver biopsy. Comparison between groups was done using χ 2 or Fisher’s exact test for categorical variables and Wilcoxon test for continuous variables. Receiver operating characteristic (ROC) curve was calculated to assess diagnostic accuracy. Statistical significance was set at p

Early mythology depicts two saints in a life-anddeath struggle to save a limb from a foregone fate. Saints Cosmos and Damien replaced a cancerous leg with a limb from a deceased Moor. This illustration was mere fantasy until the latter part of the previous century with the seminal surgeries performed by Dr. Joseph Murray on identical twins and, later, Dr. Starzl’s pioneering orthotopic liver transplant (OLT). Immunosuppression itself has come from the dark ages to where it stands today: a careful balancing act between toxicity and rejection. 1-3 This article is designed as an overview of current immunosuppression in OLT and will not delve into areas such as basic science or pipeline preview. The first attempts at whole liver grafting were carried out in 1955 with auxiliary grafts. This involved insertion of an extra liver at an ectopic location. This approach left the diseased liver intact. Early results, however, were disappointing. This early experience in the animal model and later attempts in humans led to the development of the OLT model. This was first attempted in 1963 in humans and today is the primary model for liver transplantation. 4 Early immunosuppression was suboptimal at best. Corticosteroids and azathioprine were used in combination by Starzl et al. in his first 5 transplants. The majority of the Colorado series from 1963 to 1976 received corticosteroids, azathioprine, and antilymphocyte globulin. A total of 170 patients were transplanted, and approximately 50% were children. Patients were divided into 3 time-based series. Series 1 (1963-1976, 111 patients) had a 1-year survival rate of 28.8%, Series 2 (1976-1978, 30 patients) had a 1-year survival rate of 50%, and the Series 3 (1978-1979, 29 patients) had a 1-year survival rate of 34.5%. Variations on these approaches included thoracic duct drainage or cyclophosphamide, though neither produced significant advantage. The Cambridge University group reported on a series from 1968 to 1980 with a total of 93 patients, with a 1-year survival rate of 23.7%. The lower survival rate may have been due to the lower rate of pediatric patients transplanted by the Cambridge group. 5,6 This time frame has been referred to as the precyclosporine (CyA) era (Fig. 1).

B-cell non-Hodgkin's lymphoma (B-NHL) is a well-documented complication of hepatitis C virus (HCV) infection. Marginal zone (mucosa-associated lymphoid tissue; MALT) lymphomas constitute a less common type of B-NHL. In this article, we report a case of liver MALT in a cirrhotic patient, incidentally discovered after liver transplantation (LT). We discuss pertinent diagnostic and management strategies in this clinical setting.

Recent clinical trials have documented the short-term safety of steroid avoidance (SA) in kidney transplant recipients. Since July 2003, we have used a SA immunosuppression protocol for low-risk kidney transplant recipients. Eligibility criteria are age > or = 18, primary transplant (living or deceased donor), and tacrolimus started by postoperative day 3. Recipients were excluded if peak/current PRA was >50%/20%, or if they had a positive flow crossmatch, or if they had the recent use of corticosteroids (