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The increasing prevalence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) affects both recipient and donor populations in liver transplantation. Presently, it is unclear whether transplantation of macrosteatotic allografts is affected by the metabolic milieu of liver transplant recipients. This study investigates fatty liver disease at the intersection of donor and recipient. A retrospective review of the Organ Procurement and Transplantation database identified 5167 NASH and 26,289 non-NASH transplant recipients who received transplants from January 1, 2004, to June 12, 2020. A total of 12,569 donors had allografts with no macrosteatosis (

BACKGROUND: US contrast agents are gas-filled microbubbles (MBs) that can be locally destroyed by using external US. Among other bioeffects, US-triggered MB destruction, also known as UTMD, has been shown to sensitize solid tumors to radiation in preclinical models through localized insult to the vascular endothelial cells. PURPOSE: To evaluate the safety and preliminary efficacy of combining US-triggered MB destruction and transarterial radioembolization (TARE) in participants with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: In this pilot clinical trial, participants with HCC scheduled for sublobar TARE were randomized to undergo either TARE or TARE with US-triggered MB destruction 1–4 hours and approximately 1 and 2 weeks after TARE. Enrollment took place between July 2017 and February 2020. Safety of US-triggered MB destruction was evaluated by physiologic monitoring, changes in liver function tests, adverse events, and radiopharmaceutical distribution. Treatment efficacy was evaluated by using modified Response Evaluation Criteria in Solid Tumors (mRECIST) on cross-sectional images, time to required next treatment, transplant rates, and overall survival. Differences across mRECIST reads were compared by using a Mann-Whitney U test, and the difference in prevalence of tumor response was evaluated by Fisher exact test, whereas differences in time to required next treatment and overall survival curves were compared by using a log-rank (Mantel-Cox) test. RESULTS: Safety results from 28 participants (mean age, 70 years ± 10 [standard deviation]; 17 men) demonstrated no significant changes in temperature (P = .31), heart rate (P = .92), diastolic pressure (P = .31), or systolic pressure (P = .06) before and after US-triggered MB destruction. No changes in liver function tests between treatment arms were observed 1 month after TARE (P > .15). Preliminary efficacy results showed a greater prevalence of tumor response (14 of 15 [93%; 95% CI: 68, 100] vs five of 10 [50%; 95% CI: 19, 81]; P = .02) in participants who underwent both US-triggered MB destruction and TARE (P = .02). CONCLUSION: The combination of US-triggered microbubble destruction and transarterial radioembolization is feasible with an excellent safety profile in this patient population and appears to result in improved hepatocellular carcinoma treatment response. © RSNA, 2020

Rates of simultaneous liver kidney (SLK) transplantation in the United States have progressively risen. On 8/10/17, the Organ Procurement and Transplantation Network implemented a policy defining criteria for SLK, with a 'Safety Net' to prioritize kidney allocation to liver recipients with ongoing renal failure. We performed a retrospective review of the United Network for Organ Sharing (UNOS) database to evaluate policy impact on SLK, kidney after liver (KAL) and kidney transplant alone (KTA). Rates and outcomes of SLK and KAL transplants were compared, as was utilization of high-quality kidney allografts with Kidney Donor Profile Indices (KDPI) < 35%. Here, SLK transplants comprised 9.0% and 4.5% of total post-policy liver and kidney transplants compared to 10.2% and 5.5% prior. Policy enactment did not affect 1-year graft or patient survival for SLK and KAL populations. Less post-policy SLK transplants utilized high-quality kidney allografts; in all transplant settings, outcomes using high-quality grafts remained stable. These findings suggest that policy implementation has reduced kidney allograft use in SLK transplantation, although both SLK and KAL rates have recently increased. Despite decreased high-quality kidney allograft use, SLK and KAL outcomes have remained stable. Additional studies and long-term follow-up will ensure optimal organ access and sharing.

Background: A modified Appleby procedure for pancreatic body tumors relies upon collateral vessels maintaining blood flow to the proper hepatic artery (PHA) through the pancreaticoduodenal arcade (PDA) off of the superior mesenteric artery (SMA). Compression of the celiac axis by the median arcuate ligament (MAL) promotes the expansion of collateral vessels without preoperative intervention. Case Presentation: A 51-year-old male with asymptomatic compression of the celiac artery presented with new onset insulin-dependent diabetes mellitus. He underwent imaging that demonstrated a locally advanced pancreatic body tumor that encased the superior mesenteric vein and portal vein confluence and involved the common hepatic artery. He had an adequate response to neoadjuvant FOLFIRINOX chemotherapy and underwent an uncomplicated modified Appleby procedure with a margin negative resection. Hepatic blood flow was adequate through the PHA as a result of collateralization of blood flow through the PDA off the SMA. The enhanced collateralization appeared to have occurred secondary to compression of the celiac axis by the MAL. Conclusions: Herein we present a unique case in which improved collateral blood flow through the PDA and the gastroduodenal artery to the PHA occurred due to celiac artery compression by the MAL. This vascular anomaly fortuitously improved the ability to achieve an R0 resection of a locally advanced pancreatic adenocarcinoma of the body of the pancreas by a modified Appleby procedure.

Background: Solid pseudopapillary tumors (SPTs) of the pancreas are uncommon neoplasms, first reported in 1934, well described by Frantz in 1959, and later further characterized by Hamoudi in 1970. Ninety percent of these tumors occur in young females in their second to third decade of life. An interesting case of a persistent solid pseudopapillary neoplasm is described in this report. Case presentation: A 24-year-old woman from a Middle Eastern country presented with an 8.2 × 7.6 cm heterogeneous-enhancing lesion growing within the uncinate process of the pancreas. She had first experienced symptoms at the age of 12 years. Imaging studies showed that the mass closely abutted the superior mesenteric vein as well as the superior mesenteric artery (SMA). The patient underwent an open cholecystectomy and a classic pancreaticoduodenectomy. During the resection, the SMA was transected due to tumor adherence. The vessel was subsequently reapproximated in an end-to-end manner. On the first postoperative day, thrombosis of the SMA occurred and a bile leak developed. The patient returned to the operating room for SMA embolectomy and for repair of a hepaticojejunostomy leak, with redo of the biliary-enteric anastomosis. Histopathological examination showed solid pseudopapillary-arranged cells and cystic areas, showing strong cellular immunoreactivity for CD56, CD10, vimentin, and β-catenin, and weak diffuse staining for synaptophysin. The tumor stained negative for chromogranin A, trypsin, AE1/AE3, and E-cadherin. Molecular genetic analysis was negative for the MYB gene deletion. At nearly 1 year of follow-up, the patient is well with no evidence of tumor recurrence. Conclusion: SPTs of the pancreas should be included in the differential diagnosis of pancreatic tumors, especially in young women.

Ex situ liver resection is an uncommon procedure but offers an opportunity for R0 surgical resection of liver tumors that are otherwise unresectable. Liver insufficiency following extensive resections is a risk in this patient population; consequently, all measures should be taken to prevent this highly morbid complication. We report a case of a patient with an extensive cholangiocarcinoma involving all three hepatic veins that required ex vivo resection and liver autotransplantation to achieve an R0 resection. Postoperatively, the patient demonstrated signs of worsening liver function that, in addition to standard medical therapy, underwent a brief treatment with molecular adsorbent recirculating system (MARS) therapy. Although the role of MARS remains unclear, the patient tolerated it well and her liver graft dysfunction and hepatic encephalopathy slowly resolved. The patient was discharged to a rehabilitation facility. She is currently alive and well with no evidence of recurrence 3 years later. We present a review of the literature on ex situ resection and liver autotransplantation. In addition to numerous case reports, there are a few moderate series of ex situ resection and autotransplantation. We suggest that the use of artificial liver devices, if indicated, in the postoperative ex situ resection liver autotransplant patient may assist in the support of the patient while the transplanted liver remnant recovers.

Background In this study, we present our experience with ureteral complications requiring revision surgery after renal transplantation and compare our results to a matched control population. Methods We performed a retrospective analysis of our database between 1997 and 2012. We divided the cases into early (

Adiponectin has antidiabetic properties, and patients with obesity, diabetes, and insulin resistance have low plasma adiponectin levels. However, although kidney disease is associated with insulin resistance, adiponectin is elevated in end-stage renal disease. Here we determine whether adipose tissue production of adiponectin is increased in renal disease in a case-control study of 36 patients with end-stage renal disease and 23 kidney donors. Blood and tissue samples were obtained at kidney transplantation and donation. The mean plasma adiponectin level was significantly increased to 15.6 mg/ml in cases compared with 8.4 mg/ml in controls. Plasma levels of the inflammatory adipokines tumor necrosis factor α, interleukin 6, and high-sensitivity C-reactive protein were significantly higher in cases compared with controls. Adiponectin mRNA and protein expression in visceral and subcutaneous fat were significantly higher in cases than controls, while adiponectin receptor-1 mRNA expression was significantly increased in peripheral blood cells, muscle, and adipose tissue in cases compared with controls. Thus, our study suggests that adipose tissue production of adiponectin contributes to the high plasma levels seen in end-stage renal disease.

Background/Objective: Post-transplant diabetes mellitus (PTDM) is both common and associated with poor outcomes after kidney transplantation. Our objective was to examine relationships of uremia-associated inflammation and adiponectin with PTDM. Methods: Nondiabetic kidney transplant patients were enrolled with donor controls. Inflammatory cytokines and adiponectin were measured before and after transplantation. Adipose tissue was obtained for gene expression analysis. Glucose transport was quantified in vitro in C2C12 cells following cytokine exposure. The patients were monitored up to 12 months for PTDM. Results: We studied 36 controls and 32 transplant patients, of whom 11 (35%) developed PTDM. Compared to controls, plasma TNFα, IL-6, MCP-1, and CRP levels were higher in transplant patients (p < 0.01). In multivariable analysis, TNFα plasma levels before transplantation were associated with development of PTDM (OR = 2.03, p = 0.04). Visceral adipose tissue TNFα mRNA expression was higher in transplant patients than controls (fold change 1.33; p < 0.05). TNFα mRNA expression was also higher in patients who developed PTDM than in those who did not (fold change 1.42; p = 0.05), and adiponectin mRNA expression was lower (fold change 0.48; p < 0.05). The studies on the C2C12 cells demonstrated an increase in glucose uptake following exposure to adiponectin and no significant change after exposure to TNFα alone. Concomitant TNFα and adiponectin exposure blunted adiponectin-induced glucose uptake (11% reduction; p < 0.001). Conclusion: Our in vitro and clinical observations suggest that TNFα could contribute to PTDM through an effect on adiponectin. Our study proposes that inflammation is involved in glucose regulation after kidney transplantation.

The preimplantation kidney biopsy affects utilization by diagnosing glomerulosclerosis, interstitial fibrosis (IF), arteriosclerosis, and arteriolar hyalinosis. Organ procurement organizations (OPOs) determine whether a donor warrants this biopsy and the donor hospital pathologists (DHPs) report on an OPO-specific pathology interpretation form. Biopsy slides from 40 deceased donor kidneys transplanted at our institution were used to compare interpretations between our transplant pathologist and the DHPs. Thirty-three of these kidneys also had post-perfusion biopsies (PPB). All 58 OPOs were queried for criteria used to request a preimplantation biopsy, and their pathology interpretation forms were also analyzed. The transplant and DHPs had substantial agreement for percent glomerulosclerosis with 75% of biopsies being interpreted within five percentage points. Concordance for IF was poor. The DHP rarely reported arterial pathology. Seventy percent of preimplantation and PPB were read similarly for glomerulosclerosis; concordance for other lesions was weaker. There were no cues for arterial disease on our OPO's pathology interpretation form. Criteria for obtaining a preimplantation biopsy lacked uniformity for the 21 OPOs with a self-generated policy. The pathology interpretation forms varied widely among the OPOs. Current OPO practices with regard to the preimplantation biopsy should be improved.

Robotic-assistance did not improve outcomes associated with laparoscopic donor nephrectomy in this study., Objective: To examine donor and recipient outcomes after right-sided robotic-assisted laparoscopic donor nephrectomy (RALDN) compared with standard laparoscopic donor nephrectomy (LDN) and to determine whether robotic-assistance enhances LDN. Materials & Methods: From December 2005 to January 2011, 25 patients underwent right-sided LDN or RALDN. An IRB-approved retrospective review was performed of both donor and recipient medical charts. Primary endpoints included both intraoperative and postoperative outcomes. Results: Twenty right-sided LDNs and 5 RALDNs were performed during the study period. Neither estimated blood loss (76.4mL vs. 30mL, P=.07) nor operative time (231 min vs. 218 min, P=.61) were significantly different between either group (LDN vs. RALDN). Warm ischemia time for LDN was 2.6 min vs. 3.8 min for RALDN (P=.44). Donor postoperative serum estimated glomerular filtration rates (eGFR) were similar (53 vs. 59.6mL/min/1.73m2, LDN vs. RALDN, P=.26). For the recipient patients, posttransplant eGFR were similar at 6 months (53.4 vs. 59.8mL/min/1.73m2, LDN vs. RALDN, P=.53). Conclusion: In this study, robotic-assistance did not improve outcomes associated with LDN. Larger prospective studies are needed to confirm any perceived benefit of RALDN.

Giant splenic artery pseudoaneurysms (≥5 cm in size) are rare entities. We document the successful operative management of one of the largest splenic artery pseudoaneurysms (18 cm) ever reported as well as review the world literature on the subject. Our literature review identified 160 cases of splenic artery pseudoaneurysm in the last 43 years. These ranged in size from 0.3 to 17 cm, and of these, 18 (11%) were 5 cm or larger. The majority of patients underwent treatment, either endovascularly or with open surgery, and their outcomes were independent of presenting symptoms or size. Giant splenic artery pseudoaneurysms are uncommon, most often caused by pancreatitis, trauma, or iatrogenic etiologies and typically present with vague constitutional symptoms, or occasionally with hemorrhage. Most can be treated endovascularly, though in our case this was not possible due to the presence of celiac artery occlusion with retrograde filling of the pseudoaneurysm from superior mesenteric artery collaterals. Ultimately, we opted for an open technique, with supraceliac aortic control prior to manipulation and resection of the pseudoaneurysm. Our recommendation is that splenic artery pseudoaneurysms should be repaired when encountered, regardless of aneurysm size at presentation.

Objective: To quantify the independent association between obesity and access to liver transplantation. Background: Obesity is associated with higher complication rates, longer hospitalization, and worse survival after liver transplantation. Nevertheless, transplantation provides survival benefit to patients with end-stage liver disease, regardless of body mass index (BMI). We hypothesized that, despite survival benefit, providers were reluctant to transplant obese patients because of the inherent difficulty of these cases and their inferior outcomes. Our goal was to quantify the independent association between BMI and waiting time for orthotopic liver transplantation as a surrogate marker for this reluctance. Methods: We studied 29,136 wait-list candidates in the model for end-stage liver disease (MELD) era, categorized as severely obese (BMI 35–40), morbidly obese (BMI 40–60), and reference (BMI 18.5–35). All models were adjusted for factors relevant to the allocation system, factors possibly influencing access to healthcare, and factors biologically related to disease progression and outcomes. Results: The odds of receiving a MELD exception were 30% lower in severely obese and 38% lower in morbidly obese patients. Similarly, the likelihoods of being turned down for an organ were 10% and 16% higher, and the rates of being transplanted were 11% and 29% lower in severely obese and morbidly obese patients, respectively. Conclusions: Current practice seems to indicate a reluctance to transplant obese patients. If indeed as a community we feel that liver allografts should not be distributed to patients with excessive postoperative risk, we should consider expressing this as a formal change to our allocation policy rather than through informal practice patterns.

When considering advocacy of split-liver transplantation, it is important to understand whether comparable outcomes can be achieved. The goal of this study was to identify donor and transplant characteristics predictive of comparable outcomes by risk factor analysis. Using the United Network for Organ Sharing/ Organ Procurement and Transplantation Network data base between January 1996 and May 2006, first time adult/child split cases (568 adults, 508 children) were examined. In multivariate analysis, recipient medical condition (hospitalization), status 1 assignment, ABO incompatibility, donor age (>40 years), donor body weight (≤40 kg), calculated whole graft volume to recipient body weight ratio (cGRWR ≤1.5%) and no sharing between centers were significant risk factors in adult recipients. Recipient diagnosis of tumor, dialysis prior to transplant, recipient body weight (≤6 kg), donor age (>30 years), donor history of cardiac arrest after declaration of death and cold ischemia time (CIT > 6 h) increased the risk of graft failure in pediatric recipients. The livers from young donors showed comparable outcomes to whole deceased liver transplantation (LT) when other transplant-related risk factors were minimized in adult recipients. Reducing CIT is important to obtain comparable outcomes to living donor LT in pediatric recipients.

Several treatment options exist for the management of Budd-Chiari syndrome (BCS), yet the relative role and timing of liver transplantation (LT) remain poorly defined. Small case series published to date have not been able to delineate the impact of comorbidities and thromboembolic complications of BCS on survival after LT. To better understand the outcomes after LT for BCS, we analyzed 510 liver transplants performed for this disease in the United States between 1987 and 2006. Risk factors predicting graft loss or patient death included increased recipient age, hyperbilirubinemia, elevated creatinine, life support or hospitalization at the time of transplantation, prior transplantation, prior abdominal surgery, increased donor age, and prolonged cold ischemic time (CIT). Prior transjugular intrahepatic portosystemic shunt (TIPS) was not associated with worse outcomes. Transplantation in the Model for End-Stage Liver Disease (MELD) era was associated with significantly lower risk of graft loss (hazard ratio [HR], 0.50; 95% confidence interval [CI], 0.30-0.86; P = 0.012) and death (HR, 0.52; 95% CI, 0.29-0.93; P = 0.027). Similarly, MELD era was associated with significantly lower risk of early graft loss (odds ratio [OR], 0.35; 95% CI, 0.16-0.79, P = 0.012) and early death (odds ratio, 0.37; 95% CI, 0.14-0.95; P = 0.040). However, patients with BCS transplanted in the MELD era were less likely to have life support, hospitalization, prior transplants, and prolonged cold ischemia times. In conclusion, outcomes of LT for BCS are excellent, with further improvements since 2002 associated with a selection shift imposed by MELD-based organ allocation.

Biliary complications after liver transplantation (LT) using organs retrieved from donors after cardiac death are not well characterized. The aim of this study was to evaluate the severity of biliary complications and outcomes after donation after cardiac death liver transplantation (DCD-LT). A retrospective evaluation of 20 DCD-LTs from 1997-2006 was performed. The recipient age was 53+/-8.7, and the donor age was 35+/-11 years. The warm ischemia time, cold ischemia time, peak alanine aminotransferase level, and peak aspartate aminotransferase level were 33+/-12 minutes, 8.7+/-2.7 hours, 1757+/-1477 U/L, and 4020+/-3693 U/L, respectively. The bilirubin and alkaline phosphatase levels at hospital discharge after LT were 3.2+/-5.4 mg/dL and 248+/-200 U/L, respectively. During a median follow-up of 7.5 months (range: 1-73), 5 patients (25%; 1 death after re-LT) died (3 from sepsis, 1 from recurrent hepatocellular carcinoma at 4 months, and 1 from a cardiac event at 46 months), and additionally, 4 patients (20%) required re-LT (1 because of hepatic artery thrombosis, 1 because of primary graft nonfunction, and 2 because of biliary strictures). Twelve (60%) developed biliary complications, and of these, 11 (55%) had serious biliary complications. The biliary complications were as follows: a major bile leak for 2 patients (10%; both eventually underwent retransplantation), anastomotic strictures for 5 patients (25%), hilar strictures for 7 patients (35%), extrahepatic donor duct strictures for 9 patients (45%), intrahepatic strictures for 10 patients (50%), stones for 1 patients (5%), casts for 7 patients (35%), and debris for 2 patients (10%). More than 1 biliary complication was seen in most patients, and these were unpredictable and required multiple diagnostic or therapeutic procedures. Serious biliary complications are common after DCD-LT, and research should focus on identifying donor and recipient factors that predict and prevent serious biliary complications.

Pancreatic body and tail ductal adenocarcinomas are often diagnosed with local vascular invasion of the celiac axis (CA) and its various branches. With such involvement, these tumors have traditionally been considered unresectable. The modified Appleby procedure allows for margin negative resection of some such locally advanced tumors. This procedure involves distal pancreatectomy with en bloc splenectomy and CA resection and relies on the presence of collateral arterial circulation via an intact pancreaticoduodenal arcade and the gastroduodenal artery to maintain prograde hepatic arterial perfusion. When the resultant collateral circulation is inadequate to provide sufficient hepatic and gastric arterial inflow, arterial reconstruction (AR) is necessary to “supercharge” the inflow. Herein, we review all reported cases of AR with modified Appleby procedures that we have identified in the literature, and we report our experience of three recent cases with arterial reconstruction including two cases with arterial bypasses not requiring interposition grafting. Perioperative and oncologic outcomes from our Institutional Review Board-approved database of pancreatic resections at the Thomas Jefferson University were reviewed. Additionally, PubMed search for cases of distal or total pancreatectomy with celiac axis resection and concurrent AR was performed. From the literature, 12 reports involving 28 patients were identified of distal and total pancreatectomy with AR after CA resection. The most common AR in the literature, performed in 12 patients, was a bypass from the aorta to the common hepatic artery (CHA) using a variety of interposition conduits. In our institutional experience, patient #1 had a primary side-to-end aorto-CHA bypass, patient #2 had a primary end-to-end bypass of the transected distal CHA to the left gastric artery in the setting a replaced left hepatic artery, and patient #3 required an aortic to proper hepatic artery bypass with saphenous vein graft and portal venous reconstruction. All patients recovered from their operations without ischemic complications, and they are currently 16, 15, and 13 months post-op, respectively. The criteria for resectability in patients with locally advanced pancreatic body and tail neoplasms are expanding due to increasing experience with AR in the setting of the modified Appleby procedure. When performing AR, primary arterial re-anastomosis may be considered preferable to interposition grafting as it decreases the potential for the infectious and thrombotic complications associated with conduits and it reduces the number of vascular anastomoses from two to one. Consideration must also be given to normal variant anatomy of the hepatic circulation during operative planning as the origin of the left gastric artery is resected with the CA. The modified Appleby procedure with AR, when used in appropriately selected patients, offers the potential for safe, margin negative resection of locally advanced pancreatic body and tail tumors.

BACKGROUND Liver transplantation from donation after cardiac death (DCD) donors is an increasingly common approach for expansion of the donor organ supply. However, transplantation with DCD livers results in inferior graft survival. In this study, we examined donor and recipient characteristics that are associated with poor allograft outcomes and present a set of criteria that permit allograft survival that is comparable to that of donation after brain death (DBD) grafts in both low- and high-risk recipients. METHODS The United Network for Organ Sharing/Organ Procurement and Transplantation Network Liver Transplantation Registry between January 1996 and March 2006 was investigated. Adult DCD liver transplants (n = 874) were included. RESULTS A DCD risk index was developed using the statistically significant factors from a multivariate Cox model: history of previous transplantation, life support status at transplantation, donor age, donor warm ischemia time (DWIT), and cold ischemia time (CIT). Favorable DCD donor criteria were donor age < or =45 years, DWIT < or =15 min, and CIT < or =10 hr. Four risk groups were developed based upon index scores that showed different graft survival. Graft survival of the favorable DCD group (84.9% at 1 year, 75.2% at 3 years, and 69.4% at 5 years) was comparable to that for DBD liver transplantation irrespective of recipient condition. Increasing donor age was more highly predictive of poor outcomes in DCD compared to DBD, especially in recipients in poor preoperative condition. CONCLUSIONS DCD livers from young donors with short DWIT and CIT should be given greater consideration in order to expand the number of available donor organs.

The occurrence of post renal transplant lymphocele is variable and the best approach to treatment is not well defined. The purpose of this study was to find out the incidence of post transplant lymphocele at our centre, identify demographic or surgical factors that may have influenced lymphocele formation, and distinguish the best approach to treatment. The charts of 138 consecutive renal transplant recipients from 1996 to 2001 were retrospectively reviewed. The demographic characteristics, comorbid illnesses, occurrence of lymphocele and its treatment modality were recorded. A total of 36 (26%) patients developed lymphoceles. There was a significant relationship between an increased body mass index (BMI) and lymphocele occurrence (P > 0.01). The recurrence rate with drainage alone was 33%, which decreased to 25% with sclerotherapy. In comparison, both laparoscopic and open surgical marsupialization had a much lower but similar recurrence rate of 12%. The laparoscopic method had less morbidity, a shortened hospital stay, and less infection than open surgery.

Late allograft failure (LAF) is a common cause of end stage renal disease. These patients face interrelated challenges regarding immunosuppression management, risk of graft intolerance syndrome (GIS), and sensitization. This retrospective study analyzes sensitization, pathology, imaging, and transfusion requirements in 33 LAFs presenting either with GIS (22) or grafts remaining quiescent (11). All patients underwent immunosuppression weaning to discontinuation at LAF. Profound increases in sensitization were noted for all groups and occurred in the GIS group prior to transplant nephrectomy (TxN). Patients with GIS experienced a major upswing in sensitization at, or before the time of their symptomatic presentation. For both GIS and quiescent grafts, sensitization appeared to be closely linked to immunosuppression withdrawal. Most transfusion naive patients became highly sensitized. Fourteen patients in the GIS group underwent TxN which revealed grade II acute cellular rejection or worse, with grade 3 chronic active T-cell-mediated rejection. Blinded comparisons of computed tomography scan of GIS group revealed swollen allografts with fluid collections compared with the quiescent allografts (QAs), which were shrunken and atrophic. The renal volume on imaging and weight of explants nearly matched. Future studies should focus on interventions to avoid sensitization and GIS.

Introduction Extracorporeal membrane oxygenation has become rescue therapy for adults with overwhelming cardiac and/or respiratory failure. Not all patients are saved, creating a new cohort of potential organ donors. This study examines the outcomes of liver and kidney allografts procured from donors on extracorporeal membrane oxygenation (ECMO). Methods A retrospective review was conducted through the local organ procurement organization. Donors on ECMO prior to notification were classified into donation after brain death (DBD) and donation after cardiac death (DCD). We compared short-term outcome data against published standards. Results Between 1995 and 2012, 97 organs were procured from 41 donors supported on ECMO. There were 68 kidneys donated, 51 were transplanted and 17 discarded. Excluding extended criteria donors, 29 DBD and 13 DCD kidneys were transplanted from donors supported on ECMO. Delayed graft function occurred in 34% of DBD kidneys and 38% of DCD kidneys. Kidney allograft survival at one yr was 93%. Twenty-four livers were procured, nine discarded, and 15 transplanted. Ninety-three percent of liver transplant recipients were alive with graft function at one yr. Conclusions Donation after brain death kidneys procured from donors on ECMO perform similarly to non-ECMO organs with regard to delayed graft function (DGF), one-yr graft survival and function. Livers from ECMO donors have a higher discard rate than non-ECMO donors, but function similarly at six months and one yr.

A 74-year-old woman was seen by her primary care physician for dull epigastric and right upper quadrant abdominal pain of 1-year duration. Routine laboratory values were within normal limits. The patient underwent ultrasonography of the abdomen, and 2 cystic lesions were discovered in the liver. Magnetic resonance imaging of the abdomen revealed 2 multiloculated cystic lesions in segments IV and V of the liver (Figure, A). Additional laboratory values included normal carcinoembryonic antigen and cancer antigen 19-9 levels. Percutaneous aspiration with a biopsy of one of the cystic lesions was performed that revealed atypical cells suspicious for malignancy. The patient was then referred for management to our institution, where she underwent an exploratory laparotomy and enucleation of these 2 complex multiloculated cystic lesions (Figure, B).

The regulatory benefit of apoptosis (activation-induced cell death, AICD) in T cells may be impacted by immunosuppressive agents. We examined this for mycophenolate mofetil (MMF) compared with cyclosporine (CYA). Peripheral blood leukocytes (PBL) were stimulated by either Staph enterotoxin B (SEB) or by anti-CD3 plus anti-CD28. Cell division analysis (sequential reduction in carboxyflourescein diacetate succinimidyl ester, CFSE) was used to measure proliferation and determine status of different cell generations. Apoptosis was measured by annexin V staining, and FasL expression by anti-FasL antibody staining, of activated cells using flow cytometry. CSA and mycophenolic acid (MPA, the active agent of MMF) were added in titration in 3-day cultures. We found that CSA caused diminution in apoptosis but MPA increased it with SEB stimulation. The CSA effect on apoptosis was present when a more calcineurin-dependent stimulus. anti-CD3+ anti-CD28, was used but the MPA effect was less, producing a decrease only in the undivided cells. To look more directly at the differential effect on calcineurin-dependent AICD gene induction of the two agents, we measured Fas-L expression with anti-CD-3 + CD28 stimulation, and confirmed that CYA caused a major decrement in appearance of Fas-L, whereas MPA caused a converse accumulation of it. This seems to be explained by the block more distal in cell activation, resulting in a build-up of a precursor in the activation pathways. We conclude that MMF treatment may be rationale as an adjunct to calcineurin inhibitor treatment because of its converse effect on T cell regulatory apoptosis.

Liver transplantation is a successful therapeutic option for patients with chronic liver disease and liver failure in that 1-year survival is greater than 80%. Orthotopic transplantation is usually performed from a cadaveric or living adult donor. The necessary evaluation of recipients and donors prior to transplantation can be successfully performed with computed tomography (CT). CT is useful in determining clinically relevant information for recipients such as size of the caudate lobe, exclusion of advanced hepatocellular carcinoma and other malignancy, patency of the venous system, presence of perihepatic varices, patency of the celiac artery, exclusion of splenic artery aneurysm, and position of iatrogenic venous shunts. CT in living donors may help to determine clinically relevant information about variant hepatic arterial anatomy, source of the artery to segment IV, intraparenchymal anatomy of the hepatic veins and accessory hepatic veins, trifurcation of the portal vein or hepatic duct, liver volume, and fatty change of the parenchyma. Surgical approaches and the imaging findings that influence management are reviewed.

BACKGROUND Immunosuppression involves the nature of the immunosuppressive agents and individual differences in patient factors. We investigated whether the effect of mycophenolate mofetil (MMF) is measurable using an in vitro measure of immunocompetence and related its effects to cyclosporine (CsA) in vitro. METHODS Liver or kidney transplant recipients receiving prednisone; CsA or tacrolimus; and MMF, azathioprine (AZA), or neither, were studied. Immunocompetence was assessed by one-way mixed lymphocyte culture using patients' peripheral blood leukocytes (PBL) and three validated stimulators. The effect of immunosuppressive agents added in vitro on normal PBL stimulation by Staphylococcus enterotoxin B was determined by the carboxyfluorescein diacetate succinimidyl ester measurement of division. RESULTS Patients receiving MMF had an average immunocompetence level of 12+/-23, compared with 39.7+/-65 and 25.5+/-42 for those receiving AZA or neither AZA nor MMF, respectively. Thus, there was an approximately 80% suppression of the response in the MMF group. Assessment of normal cell division revealed that CsA allowed multiple cell generations but suppressed the numbers of cells in each, whereas MMF blocked proliferation into subsequent generations. Addition of clinically relevant levels of mycophenolic acid, the active agent for MMF, added to more moderate levels of CsA, was required to achieve greater than 80% suppression, consistent with the degree of immunocompetence depression measured in patients. CONCLUSIONS These data provide the novel finding that the effect of MMF treatment on patients is measurable in their PBL as decreased immunocompetence in vitro. The effect of MMF on normal PBL approximates the 80% inhibition that we found in patients. Moreover, the effect of MMF on cell division provides a rationale for the superior effectiveness of regimens including MMF.

Portopulmonary hypertension (PPHTN) is no longer an absolute contraindication to orthotopic liver transplantation (OLT). The pre-OLT management of patients with PPHTN requires early diagnosis and chronic therapy with intravenous epoprostenol to decrease pulmonary vascular resistance (PVR). Close follow-up is necessary to reassess pulmonary artery pressures (PAPs) and evaluate right ventricular (RV) function. This assists in the optimal timing of OLT. Successful management also necessitates reassessment of pulmonary artery hemodynamics just before OLT, with clearly defined parameters used to determine whether to proceed. Even with the intraoperative and postoperative availability of potent pulmonary vasodilators, clinical management may be suboptimal in reducing PAP. Adequate reduction in PVR and improvement in RV function in response to chronic epoprostenol therapy may facilitate successful OLT. We present a case report and review the limited experience with this treatment.

Laparoscopic live donor nephrectomy was first performed clinically in 1995. The original hypothesis that provided the impetus for the development of this operation was that the reduction of postoperative pain and recuperative time would decrease logistical and financial disincentives to live kidney

Background Hyperacute rejection (HAR) and acute humoral rejection (AHR) remain recalcitrant conditions without effective treatments, and usually result in graft loss. Plasmapheresis (PP) has been shown to remove HLA- specific antibody (Ab) in many different clinical settings. Intravenous gamma globulin (IVIG) has been used to suppress alloantibody and modulate immune responses. Our hypothesis was that a combination of PP and IVIG could effectively and durably remove donor-specific, anti-HLA antibody (Ab), rescuing patients with established AHR and preemptively desensitizing recipients who had positive crossmatches with a potential live donor. Methods The study patients consisted of seven live donor kidney transplant recipients who experienced AHR and had donor-specific Ab (DSA) for one or more mismatched donor HLA antigens. The patients segregated into two groups: three patients were treated for established AHR (rescue group) and four cross-match-positive patients received therapy before transplantation (preemptive group). Results Using PP/IVIG we have successfully reversed established AHR in three patients. Four patients who were cross-match-positive (3 by flow cytometry and 1 by cytotoxic assay) and had DSA before treatment underwent successful renal transplantation utilizing their live donor. The overall mean creatinine for both treatment groups is 1.4+/-0.8 with a mean follow up of 58+/-40 weeks (range 17-116 weeks). Conclusions In this study, we present seven patients for whom the combined therapies of PP/IVIG were successful in reversing AHR mediated by Ab specific for donor HLA antigens. Furthermore, this protocol shows promise for eliminating DSA preemptively among patients with low-titer positive antihuman globulin-enhanced, complement-dependent cytotoxicity (AHG-CDC) cross-matches, allowing the successful transplantation of these patients using a live donor without any cases of HAR.

Introduction. The purposes of this study were: 1) to analyze the early results of cadaveric renal transplantation from either hepatitis C virus seropositive (HCV ) or hepatitis C virus seronegative (HCV ) donors into HCV recipients; and 2) to determine whether HCV patients with end-stage renal disease (ESRD) might benefit from receiving renal allografts from HCV donors.

Background Laparoscopic live donor nephrectomy offers advantages to the donor in terms of decreased pain and shorter recuperation. Heretofore no detailed analysis of the recipient of laparoscopically procured kidneys has been performed. The purpose of this study was to determine whether laparoscopic donor nephrectomy had any deleterious effect on the recipient. Methods. A retrospective review was conducted of all live donor renal transplantations performed from January 1995 through April 1998. The control group received kidneys procured via a standard flank approach (Open). Rejection was diagnosed histologically. Creatinine clearance was calculated using the Cockroft-Gault formula. Results. A total of 110 patients received kidneys from laparoscopic (Lap) and 48 from open donors. One-year recipient (100% vs. 97.0%) and graft (93.5% vs. 91.1%) survival rates were similar for the Open and Lap groups, respectively. A similar incidence of vascular thrombosis (3.4% vs. 2.1%, P=NS) and ureteral complications (9.1% vs. 6.3%, P=NS) were seen in the Lap and Open groups, respectively. The incidence of acute rejection for the first month was 30.1% for the Lap group and 31.9% for the Open group (P=NS). The rate of decline of serum creatinine level in the early post-transplantation period was initially greater in the Open group, but by postoperative day 4 no significant difference existed. No difference was observed in allograft function long-term. The median length of hospital stay was 7.0 days for both groups. Conclusions. Laparoscopic live donor nephrectomy does not adversely effect recipient outcome. The previously demonstrated benefits to the donor, and the increased willingness of individuals to undergo live kidney donation, coupled with the acceptable outcomes experienced by recipients of laparoscopically procured kidneys justifies the continued development and adoption of this operation.

Purpose: This study reports the authors' cumulative experience with pediatric living related orthotopic liver transplantation. Methods: The charts of all patients who received living-related liver transplantation to study complications of transplant surgery, immunosuppression, rejection, and overall survival rate were reviewed retrospectively. Results: Between November 1992 and October 1998, 30 children underwent living-related liver transplantation. Patients were between the ages of 3 months and 7 years of age (mean, 28 months). All received left lateral segmental living-related transplants. At the time of transplant, 14 of 30 patients were listed as United Network of Organ Sharing (UNOS) status 3, 11 were listed as UNOS status 2B, and 5 were listed as UNOS status 1. Indications for transplant included biliary atresia (n = 21), α-1-antitrypsin deficiency (n = 2), hepatitis C (n = 2), giant cell hepatitis (n = 2), hepatoblastoma (n = 1), valproic acid toxicity (n = 1), and hemangioendothelioma (n = 1). All donors were parents except for one uncle. There were no major donor complications. Minor complications included wound infection (n = 4), ventral hernia (n = 2), postoperative gastric dysmotility (n = 2), and 1 case of central line-related pneumothorax (n = 1). All but 4 recipients received primary tacrolimus immunosuppressive regimens, and the other 4 underwent conversion from cyclosporine. Initial tacrolimus therapy was begun at 0.15 mg/kg/dose PO/NG every 12 hours. Concomitant immunosuppression included methylprednisolone and mycophenolate mofetil. Fifty-three percent of patients experienced at least 1 episode of rejection, and 27% experienced multiple episodes. Immediate postoperative complications included primary nonfunction (n = 2), vascular thrombosis (n = 3), biliary leaks (n = 3), and infections (n = 17). Two patients (n = 2) required retransplantation. Complications of immunosuppressive therapy included persistent systemic hypertension (n = 6), renal tubular acidosis (n = 3), short-term hyperglycemia (n = 2), neurotoxicity (n = 2), nephrotoxicity (n = 2), food allergies (n = 8), and posttransplant lymphoproliferative disease (n = 4). All patients with PTLD were treated with immunosuppression reduction or withdrawal. Two of 4 had disease progression requiring chemotherapy. The majority of complications were treated with dose adjustments. There were 4 early deaths (13%): 1 of primary nonfunction, 2 of sepsis, and 1 of arrhythmia and renal failure. There was 1 late death of recurrent disease. Twenty-five patients (83%) are alive at 3 months to 6 years post-transplant. Conclusion: Living-related orthotopic liver transplantation is an effective intervention for pediatric patients with end-stage disease. J Pediatr Surg 35:9-12. Copyright © 2000 by W.B. Saunders Company.

Current models for allocation of kidneys from living non-directed donors Living non-directed (LND) donors, also known as altruistic, good Samaritan, anonymous, or benevolent community donors, are a new and rapidly growing source of solid organs for transplantation. The willingness of individuals to donate organs without a designated recipient has been unexpected, but has probably developed as a societal response to the growing crisis in organ availability. In the context of this shortage, health professionals have attempted to make the best use of kidneys from LND donors. We present a novel application of paired donation that has the potential to multiply the number of recipients who can benefi t from each LND donation. At present, there is no universally accepted system for allocation of organs from LND donors. Selection of recipients has been at the discretion of the transplant centres where LND donors have presented and has generally been guided by one of three models: donorcentric, recipient-centric, or sociocentric allocation. Each of these models is supported by valid ethical arguments. The main goal of donor-centric allocation is to ensure a successful outcome for the recipient. A good outcome provides justifi cation for medical professionals to assist a person who is not ill to put themselves in harm’s way to aid another. A positive result also gives an LND donor a sense that their eff ort was fruitful and worthwhile. However, this model dictates allocation to the healthiest patient on the transplant waiting list. These recipients are the most likely to have good outcomes on dialysis or with organs from deceased donors, and therefore are arguably the least in need. Recipient-centric allocation is based on the belief that society has a responsibility to protect its most vulnerable and disadvantaged members. Under this model, organs from LND donors are given to those patients in the greatest need, those for whom a kidney transplant might be truly life saving, or those disadvantaged under the existing system for allocation of kidneys from deceased donors. This model mainly benefi ts children, patients who have no vascular access, highly sensitised patients, and those with life-threatening medical illnesses related to dialysis. However, because the recipient-centric model accords priority to such patients, it tends to yield unacceptably poor transplant outcomes, and could lead to a negative public perception of LND donation. Under the third model, of sociocentric allocation, the LND donated organ is treated as a public resource that should be allocated in the fairest and most equitable way, irrespective of outcome or need. This rationale dictates that the recipient should be the patient at the top of the transplant waiting list administered by the United Network of Organ Sharing (UNOS). UNOS oversees the allocation of deceased donor organs in the USA, using a so-called match run algorithm that ranks potential recipients according to agreed criteria. The limitations of this model are that a patient at the top of the list will probably receive a kidney from a deceased donor in the near future, and that they will have already incurred the costs, and exposure to comorbidity, that result from a long period on dialysis. The waiting list for deceased donor kidneys can be circumvented by patients who fi nd a willing live donor. But direct donation might be complicated by diff erences in blood type and by HLA sensitivity. Some incompatible donor-recipient pairs enter into programmes that facilitate paired donation, also known as kidney paired donation. A donor and recipient who have incompatible blood groups or HLA sensitivity can be matched with another incompatible pair, to result in two compatible transplants (fi gure). Although there are many ways to match up a pool of incompatible pairs, the mathematical technique of optimisation helps to fi nd out which matches will yield the best results. Nevertheless, even in paired-donation programmes in which mathematical optimisation is applied, more than 50% of the incompatible pairs in the pool remain unmatched. In many cases, pools of incompatible donor-recipient pairs have a high proportion of patients with blood types that are hard to match and those with HLA sensitisation.

Whether liver resection or liver transplantation is optimal therapy for patients with hepatocellular carcinoma (HCC) remains undefined. A meta-analysis was conducted to answer this question. This study performed a systematic review of the published literature between January 2000 and April 2012. Nine retrospective studies, totaling 2,279 patients (989 resected and 1,290 transplanted), met the selection criteria. Older patients with larger tumors and less severe cirrhosis were identified in the resection group. At 1 year, resection demonstrated significantly higher overall [odds ratio (OR) = 1.54; 95 % confidence interval (CI), 1.19–1.98; p = 0.001], but equivalent disease-free survival (OR = 0.93; 95 % CI, 0.53–1.63; p = 0.80). At 5 years, there was no difference in overall survival (OR = 0.86; 95 % CI, 0.61–1.21; p = 0.38), but a higher disease-free survival in transplanted patients was observed (OR = 0.39; 95 % CI, 0.24–0.63; p

The preimplantation kidney biopsy affects utilization by diagnosing glomerulosclerosis, interstitial fibrosis (IF), arteriosclerosis, and arteriolar hyalinosis. Organ procurement organizations (OPOs) determine whether a donor warrants this biopsy and the donor hospital pathologists (DHPs) report on an OPO-specific pathology interpretation form. Biopsy slides from 40 deceased donor kidneys transplanted at our institution were used to compare interpretations between our transplant pathologist and the DHPs. Thirty-three of these kidneys also had post-perfusion biopsies (PPB). All 58 OPOs were queried for criteria used to request a preimplantation biopsy, and their pathology interpretation forms were also analyzed. The transplant and DHPs had substantial agreement for percent glomerulosclerosis with 75% of biopsies being interpreted within five percentage points. Concordance for IF was poor. The DHP rarely reported arterial pathology. Seventy percent of preimplantation and PPB were read similarly for glomerulosclerosis; concordance for other lesions was weaker. There were no cues for arterial disease on our OPO's pathology interpretation form. Criteria for obtaining a preimplantation biopsy lacked uniformity for the 21 OPOs with a self-generated policy. The pathology interpretation forms varied widely among the OPOs. Current OPO practices with regard to the preimplantation biopsy should be improved.

Sarcoidosis is a multisystem chronic granulomatous disease found predominantly in the lungs and lymph nodes. Its pathologic hallmark is the presence of systemic non-caseating granulomas; however, a variation of this disease known as “sarcoid-like reaction” has been described in patients with underlying cancer. Sarcoid-like reactions in patients with hepatopancreatobiliary (HPB) tumors are rare findings, with only 15 cases having been reported in the English language literature. These reactions can be found in local lymph nodes or in distant organs, and when present in patients with cancer, they can mimic metastatic disease on imaging, potentially resulting in incorrect cancer staging and management. We describe two cases of patients with HPB tumors who had distant organ disease on cross-sectional imaging suspicious for metastases, which on further workup were found to be sarcoid-like reactions. We also discuss malignancy-induced sarcoid-like reactions and provide a review of the literature of sarcoid-like reactions in the setting of HPB tumors.

Background. The spectrum of disease caused by Ehrlichia spp. ranges from asymptomatic to fatal. Awareness and early diagnosis of the infection is paramount because appropriate therapy leads to rapid defervescence and cure. If left untreated, particularly in immunosuppressed patients, ehrlichioses may result in multi-system organ failure and death. Methods. We report the second case of human monocytic ehrlichiosis (HME) in a liver transplant recipient, and review the literature. Results. The patient presented with fever and headache, had negative cultures, and despite broad-spectrum antimicrobial coverage appeared progressively septic. After eliciting a history of tick exposure we treated the patient empirically with doxycycline. The diagnosis of HME was confirmed by 1) polymerase chain reaction (PCR) for Ehrlichia chaffeensis, 2) acute and convalescent serum titers, and 3) in vitro cultivation of E chaffeensis from peripheral blood. Conclusion. Although human ehrlichioses are relatively uncommon, they are emerging as clinically significant arthropod-borne infections. Although epidemiological exposure is responsible for infection, immunosuppression makes patients more likely to succumb to disease. A high index of suspicion and early treatment results in a favorable outcome.

Budd-Chiari syndrome (BCS) is a rare form of portal hypertension characterized by hepatic venous outflow obstruction. Although hematologic disorders are the most common cause of this syndrome, to date, 30% of the cases have been classified as idiopathic. Resistance to activated protein C caused by factor V Leiden is the most common cause of thrombophilia; its role in the pathogenesis of BCS is now becoming apparent. We report successful liver transplantation in a patient with BCS caused by homozygous factor V Leiden. The patient was administered standard heparin anticoagulation until activated protein C resistance was normalized by the liver allograft. Liver transplantation corrected the thrombophilic state. The patient has excellent graft function, is not on anticoagulation therapy, and has had no recurrent venous thrombosis at 5 months posttransplantation. Activated protein C resistance caused by the factor V Leiden mutation may be responsible for idiopathic cases of BCS. To avoid unnecessary long-term anticoagulation after liver transplantation, factor V Leiden should be considered as a pathogenic factor in BCS. In addition, because of the high prevalence of factor V Leiden in the world population, cadaveric organ donors with a history of venous thrombosis should be screened for activated protein C resistance lest thrombophilia be transmitted to the recipient.

The results of orthotopic liver transplantation in patients with end-stage liver disease continue to improve. Refinements in surgical techniques represent an important part of this improvement.With the advent of split-liver and living-donor liver transplantation, inferior vena cava (IVC) preservation transitioned from being a potential option to being mandatory for many cases. Preserving the IVC can be a demanding technical maneuver in many liver transplants and several different approaches have been developed. When utilizing IVC preservation, there are several options for implantation of the graft. The piggyback technique, when feasible, is considered safe and provides hemodynamic stability for the recipient.In some cases it may be difficult to perform the piggyback technique if intense inflammatory adhesions and severe significant collateral circulation exist between the IVC and the posterior segments of the liver. In these cases, the retro-hepatic dissection can be carried out with a different approach: the infrahepatic vena cava and the confluence of the three hepatic veins can be cross-clamped en-bloc without dissection.This technique broadens the transplant surgeons' armamentarium and can be used in the setting of a very difficult retro-hepatic dissection. It is safe, and allows a shorter anhepatic phase with caval preservation.

BACKGROUND When the United Network for Organ Sharing changed its algorithm for liver allocation to the model for end-stage liver disease (MELD) system in 2002, highest priority shifted to patients with renal insufficiency as a major component of their end-stage liver disease. An unintended consequence of the new system was a rapid increase in the number of simultaneous liver-kidney transplants (SLK) being performed yearly. METHODS Adult recipients of deceased donor liver transplants (LT, n=19,137), kidney transplants (n=33,712), and SLK transplants (n=1,032) between 1987 and 2006 were evaluated based on United Network for Organ Sharing data. Recipients were stratified by donor subgroup, MELD score, pre- versus post-MELD era, and length of time on dialysis. Matched-control analyses were performed, and graft and patient survival were analyzed by Kaplan-Meier and Cox proportional hazards analyses. RESULTS MELD era outcomes demonstrate a decline in patient survival after SLK. Using matched-control analysis, we are unable to demonstrate a benefit in the SLK cohort compared with LT, despite the fact that higher quality allografts are being used for SLK. Subgroup analysis of the SLK cohort did demonstrate an increase in overall 1-year patient and liver graft survival only in those patients on long-term dialysis (> or =3 months) compared with LT (84.5% vs. 70.8%, P=0.008; hazards ratio 0.57 [95% CI 0.34, 0.95], P=0.03). CONCLUSION These findings suggest that SLK may be overused in the MELD era and that current prioritization of kidney grafts to those liver failure patients results in wasting of limited resources.

Steroid use after liver transplantation (LT) has been associated with diabetes, hypertension, hyperlipidemia, obesity, and hepatitis C (HCV) recurrence. We performed meta-analysis and meta-regression of 30 publications representing 19 randomized trials that compared steroid-free with steroid-based immunosuppression (IS). There were no differences in death, graft loss, and infection. Steroid-free recipients demonstrated a trend toward reduced hypertension [relative risk (RR) 0.84, P = 0.08], and statistically significant decreases in cholesterol (standard mean difference -0.41, P < 0.001) and cytomegalovirus (RR 0.52, P = 0.001). In studies where steroids were replaced by another IS agent, the risks of diabetes (RR 0.29, P < 0.001), rejection (RR 0.68, P = 0.03), and severe rejection (RR 0.37, P = 0.001) were markedly lower in steroid-free arms. In studies in which steroids were not replaced, rejection rates were higher in steroid-free arms (RR 1.31, P = 0.02) and reduction of diabetes was attenuated (RR 0.74, P = 0.2). HCV recurrence was lower with steroid avoidance and, although no individual trial reached statistical significance, meta-analysis demonstrated this important effect (RR 0.90, P = 0.03). However, we emphasize the heterogeneity of trials performed to date and, as such, do not recommend basing clinical guidelines on our conclusions. We believe that a large, multicenter trial will better define the role of steroid-free regimens in LT.