Portable hypothermic oxygenated machine perfusion for organ preservation in liver transplantation: A randomized, open-label, clinical trial.

BACKGROUND AND AIMS: In liver transplantation, cold preservation induces ischemia, resulting in significant reperfusion injury. Hypothermic oxygenated machine perfusion (HMP-O 2 ) has shown benefits compared to static cold storage (SCS) by limiting ischemia-reperfusion injury. This study reports outcomes using a novel portable HMP-O 2 device in the first US randomized control trial. APPROACH AND RESULTS: The PILOT trial (NCT03484455) was a multicenter, randomized, open-label, noninferiority trial, with participants randomized to HMP-O 2 or SCS. HMP-O 2 livers were preserved using the Lifeport Liver Transporter and Vasosol perfusion solution. The primary outcome was early allograft dysfunction. Noninferiority margin was 7.5%. From April 3, 2019, to July 12, 2022, 179 patients were randomized to HMP-O 2 (n=90) or SCS (n=89). The per-protocol cohort included 63 HMP-O 2 and 73 SCS. Early allograft dysfunction occurred in 11.1% HMP-O 2 (N=7) and 16.4% SCS (N=12). The risk difference between HMP-O 2 and SCS was -5.33% (one-sided 95% upper confidence limit of 5.81%), establishing noninferiority. The risk of graft failure as predicted by Liver Graft Assessment Following Transplant score at seven days (L-GrAFT 7 ) was lower with HMP-O 2 [median (IQR) 3.4% (2.4-6.5) vs. 4.5% (2.9-9.4), p =0.024]. Primary nonfunction occurred in 2.2% of all SCS (n=3, p =0.10). Biliary strictures occurred in 16.4% SCS (n=12) and 6.3% (n=4) HMP-O 2 ( p =0.18). Nonanastomotic biliary strictures occurred only in SCS (n=4). CONCLUSIONS: HMP-O 2 demonstrates safety and noninferior efficacy for liver graft preservation in comparison to SCS. Early allograft failure by L-GrAFT 7 was lower in HMP-O 2 , suggesting improved early clinical function. Recipients of HMP-O 2 livers also demonstrated a lower incidence of primary nonfunction and biliary strictures, although this difference did not reach significance.

Impact of Portable Normothermic Blood-Based Machine Perfusion on Outcomes of Liver Transplant: The OCS Liver PROTECT Randomized Clinical Trial.

IMPORTANCE: Ischemic cold storage (ICS) of livers for transplant is associated with serious posttransplant complications and underuse of liver allografts. OBJECTIVE: To determine whether portable normothermic machine perfusion preservation of livers obtained from deceased donors using the Organ Care System (OCS) Liver ameliorates early allograft dysfunction (EAD) and ischemic biliary complications (IBCs). DESIGN, SETTING, AND PARTICIPANTS: This multicenter randomized clinical trial (International Randomized Trial to Evaluate the Effectiveness of the Portable Organ Care System Liver for Preserving and Assessing Donor Livers for Transplantation) was conducted between November 2016 and October 2019 at 20 US liver transplant programs. The trial compared outcomes for 300 recipients of livers preserved using either OCS (n = 153) or ICS (n = 147). Participants were actively listed for liver transplant on the United Network of Organ Sharing national waiting list. INTERVENTIONS: Transplants were performed for recipients randomly assigned to receive donor livers preserved by either conventional ICS or the OCS Liver initiated at the donor hospital. MAIN OUTCOMES AND MEASURES: The primary effectiveness end point was incidence of EAD. Secondary end points included OCS Liver ex vivo assessment capability of donor allografts, extent of reperfusion syndrome, incidence of IBC at 6 and 12 months, and overall recipient survival after transplant. The primary safety end point was the number of liver graft-related severe adverse events within 30 days after transplant. RESULTS: Of 293 patients in the per-protocol population, the primary analysis population for effectiveness, 151 were in the OCS Liver group (mean [SD] age, 57.1 [10.3] years; 102 [67%] men), and 142 were in the ICS group (mean SD age, 58.6 [10.0] years; 100 [68%] men). The primary effectiveness end point was met by a significant decrease in EAD (27 of 150 [18%] vs 44 of 141 [31%]; P = .01). The OCS Liver preserved livers had significant reduction in histopathologic evidence of ischemia-reperfusion injury after reperfusion (eg, less moderate to severe lobular inflammation: 9 of 150 [6%] for OCS Liver vs 18 of 141 [13%] for ICS; P = .004). The OCS Liver resulted in significantly higher use of livers from donors after cardiac death (28 of 55 [51%] for the OCS Liver vs 13 of 51 [26%] for ICS; P = .007). The OCS Liver was also associated with significant reduction in incidence of IBC 6 months (1.3% vs 8.5%; P = .02) and 12 months (2.6% vs 9.9%; P = .02) after transplant. CONCLUSIONS AND RELEVANCE: This multicenter randomized clinical trial provides the first indication, to our knowledge, that normothermic machine perfusion preservation of deceased donor livers reduces both posttransplant EAD and IBC. Use of the OCS Liver also resulted in increased use of livers from donors after cardiac death. Together these findings indicate that OCS Liver preservation is associated with superior posttransplant outcomes and increased donor liver use. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02522871.

Robot-assisted kidney transplantation is a safe alternative approach for morbidly obese patients with end-stage renal disease.

BACKGROUND: Many centres deny obese patients with a body mass index (BMI) >35 access to kidney transplantation due to increased intraoperative and postoperative complications. METHODS: From August 2017 to December 2019, 73 consecutive cases of kidney transplantation in morbidly obese patients were enrolled at a single university at the initiation of a robotic transplant surgery program. Outcomes of patients who underwent robotic assisted kidney transplant (RAKT) were compared to frequency-matched patients undergoing open kidney transplant (OKT). RESULTS: A total of 24 morbidly obese patients successfully underwent RAKT, and 49 obese patients received an OKT. The RAKT group developed fewer surgical site infections (SSI) than the OKT group. Graft function, creatinine, and glomerular filtration rate (GFR) were similar between groups 1 year after surgery. Graft and patient survival were 100% for both groups. CONCLUSIONS: RAKT offers a safe alternative for morbidly obese patients, who may otherwise be denied access to OKT.

Lose Weight to Donate: Development of a Program to Optimize Potential Donors With Hepatic Steatosis or Obesity for Living Liver Donation.

BACKGROUND: Living donor liver transplantation offers an attractive option to reduce the waitlist mortality. However, in recent years, the rising prevalence of obesity and nonalcoholic fatty liver disease has posed a serious threat to the donor pool while simultaneously increasing demand for liver transplant. To our knowledge, there have been no major published studies in the United States documenting a diet and exercise intervention to expand the living donor pool. Hereby, we established a pilot program called "Lose Weight to Donate" and present our initial experience. METHODS: Our center instituted a remotely monitored diet and exercise pilot program to increase eligibility for living liver donation. Potential donors with any of the following were included: body mass index >30 kg/m2, hepatic steatosis >5% on screening MRI, or isolated hypertension. RESULTS: Over 19 mo, 7 individuals enrolled in the program of remote monitoring for at least 6-8 wk. Initial and follow-up abdominal MRI was performed in 5 of these individuals to assess steatosis, anatomy, and volume. Initial steatosis was highly variable (fat signal fraction range, 8%-26%). Follow-up MRI fat signal fraction values and hepatic volume all decreased to varying degrees. Ultimately, 2 of 7 individuals donated, whereas a third was approved, but the intended recipient was transplanted in the interim. CONCLUSIONS: These results indicate the feasibility of a remotely monitored program to expand donation in light of the rising incidence of hepatic steatosis and obesity.

Effects of Initial Hepatic Artery Followed by Portal Reperfusion Technique on Deceased Donor Liver Transplant Outcomes.

OBJECTIVES: Although initial portal vein reperfusion of a liver allograft is nearly standardized, limited data suggest initial hepatic artery reperfusion may improve hemodynamics and posttransplant outcomes. MATERIALS AND METHODS: We retrospectively reviewed orthotopic liver transplants performed between January 2013 and February 2018. Parameters of liver recipients with initial hepatic artery reperfusion were compared with those with initial portal vein reperfusion. RESULTS: Of 204 recipients, 53 (26%) were initially perfused from the hepatic artery and 151 (74%) were initially perfused from the portal vein. Demographics between groups did not differ. There were no significant differences in the incidence of acute rejection between recipients with initial hepatic artery reperfusion versus portal vein reperfusion at 3 months and 1 year (1.9% vs 7.9% and 7.5% vs 10.6%; not significant), hepatic artery thrombosis (1.9% vs 4.0% and 1.9% vs 7.3%; not significant), biliary leakage (7.5% vs 4.0% and 9.4 vs 6.6; not significant), biliary strictures (7.5% vs 5.3% and 11.3% vs 7.9%; not significant), or portal or hepatic venous thrombosis/stenosis (5.7% vs 5.3% and 7.5% vs 7.9%; not significant). Furthermore, recipients with initial hepatic artery reperfusion and portal vein reperfusion were both hospitalized for a median of 8.5 days (interquartile range, 6.5-15.5 vs 7.0-14.0 days, respectively), and both groups were in the intensive care unit for a median of 3 days (interquartile range, 2-7 vs 2-4 days, respectively). Initial hepatic artery reperfusion was associated with significantly less intraoperative packet red blood cell transfusion (median, 11.9 U [interquartile range, 11.1-13.1 U] vs 15.5 U [interquartile range, 12.9-17.9 U]; P < .001). The 2 groups did not differ in terms of patient and graft survival. CONCLUSIONS: Initial reperfusion of liver allografts with arterial, rather than portal, blood has benefits to hemodynamic stability, did not have deleterious effects on outcomes, and resulted in less intraoperative blood utilization.

Hepatic Artery Thrombosis and Takotsubo Syndrome After Liver Transplantation - Which Came First?

BACKGROUND Takotsubo syndrome is a transient, reversible, stress-induced cardiomyopathy that affects only 1.4% of liver transplant patients and can cause complications, including cardiogenic shock, arrhythmia, and thromboembolism. Hepatic artery thrombosis is also rare, affecting just 2-4% of these patients, but can have disastrous consequences. Here, we describe a case of concurrent takotsubo syndrome and hepatic artery thrombosis in a postoperative liver transplant recipient. CASE REPORT The patient was a 66-year-old man who underwent living donor liver transplantation for non-alcoholic steatohepatitis. On postoperative day 3, he became lethargic and tachycardic to the 120 s. Work-up, including EKG, troponin I, BNP, and transthoracic echocardiogram, was characteristic for takotsubo syndrome. His LVEF of 15-20% was markedly reduced compared to his baseline of 50-55% from 6 months prior. Hepatic ultrasonography showed no hepatic arterial flow, prompting emergent return to the OR, where intraoperative evaluation revealed hepatic artery thrombosis. The graft was salvaged after hepatic artery thrombectomy and arterial anastomosis revision. We are unable to determine which event caused the other in this case, as both takotsubo syndrome and hepatic artery thrombosis manifested within the same time frame. CONCLUSIONS It is important to recognize takotsubo syndrome as a potential cause of cardiac dysfunction and hepatic artery thrombosis in liver transplant patients, and also be aware that hepatic artery thrombosis can precipitate takotsubo syndrome.

Intraoperative glycemic control in patients undergoing Orthotopic liver transplant: a single center prospective randomized study.

BACKGROUND: Perioperative hyperglycemia is associated with poor outcomes yet evidence to guide intraoperative goals and treatment modalities during non-cardiac surgery are lacking. End-stage liver disease is associated with altered glucose homeostasis; patients undergoing liver transplantation display huge fluctuations in blood glucose (BG) and represent a population of great interest. Here, we conduct a randomized trial to compare the effects of strict versus conventional glycemic control during orthotopic liver transplant (OLT). METHODS: Following approval by the Institutional Review Board of the University of Michigan Medical School and informed consent, 100 adult patients undergoing OLT were recruited. Patients were randomized to either strict (target BG 80-120 mg/dL) or conventional (target BG 180-200 mg/dL) BG control with block randomization for diabetic and nondiabetic patients. The primary outcomes measured were 1-year patient and graft survival assessed on an intention to treat basis. Graft survival is defined as death or needing re-transplant (www.unos.org). Three and 5-year patient and graft survival, infectious and biliary complications were measured as secondary outcomes. Data were examined using univariate methods and Kaplan-Meir survival analysis. A sensitivity analysis was performed to compare patients with a mean BG of ≤120 mg/dL and those > 120 mg/dL regardless of treatment group. RESULTS: There was no statistically significant difference in patient survival between conventional and strict control respectively;1 year, 88% vs 88% (p-0.99), 3 years, 86% vs 84% (p- 0.77), 5 years, 82% vs 78. % (p-0.36). Graft survival was not different between conventional and strict control groups at 1 year, 88% vs 84% (p-0.56), 3 years 82% vs 76% (p-0.46), 5 years 78% vs 70% (p-0.362). CONCLUSION: There was no difference in patient or graft survival between intraoperative strict and conventional glycemic control during OLT. TRIAL REGISTRATION: Clinical trial number and registry: www.clinicaltrials.gov NCT00780026. This trial was retrospectively registered on 10/22/2008.

Macrosteatotic Allografts and Obese Recipients Have Nearly Equal Negative Impact on Liver Transplant Survival.

BACKGROUND: Our aim was to evaluate liver transplant outcomes involving donors with high macrosteatosis grafts in the obese modern liver transplant recipient population. METHODS: A high-steatosis graft was defined as donor graft macrosteatosis ≥30% on biopsy. Recipient obesity was defined as body mass index (BMI) >35 adjusted for ascites. Raw and adjusted recipient liver transplant survival were evaluated and compared between 4 cohorts: (1) high-steatosis graft in high-BMI recipient; (2) low-steatosis graft in high-BMI recipient; (3) high-steatosis graft in normal-BMI recipient; and (4) low-steatosis graft in normal-BMI recipient. RESULTS: After adjustment for multiple factors, recipient high-BMI remained an independent predictor of posttransplant mortality at 30 days (P < 0.0001) and persisted at 1 year (P = 0.009). A high-steatosis graft was the strongest independent predictor of mortality at 30 days (hazard ratio 2.05, 1.66-2.53; P < 0.0001) and that effect was diminished but persistent at 1 year (1.27, 1.10-1.46; P = 0.001). CONCLUSIONS: Recipient high-BMI and a high-steatosis graft are both significant independent and equally powerful predictors of mortality after modern liver transplant. High-steatosis grafts transplanted into obese recipients have the highest mortality. The increase in mortality associated with a high-steatosis graft into a normal-BMI recipient is similar in magnitude to a low-steatosis graft placed into a high-BMI recipient.

Geographic variation in liver transplantation persists despite implementation of Share35.

AIM: Geographic disparities persist in the USA despite locoregional organ sharing policies. The impact of national organ sharing policies on waiting-list mortality on a regional basis remains unknown. METHODS: Data on all adult liver transplants between 1 February 2002 and 31 March 2015 were obtained from the United Network for Organ Sharing/Organ and Transplantation Network. Multivariable Cox proportional hazards models were constructed in a time-to-event analysis to estimate waiting-list mortality for the pre- and post-Share35 eras. RESULTS: In the analyzed time period, 134 247 patients were listed for transplantation and 54 510 received organs (42.8%). Listing volume increased following the introduction of the Share35 organ sharing policy (15 976 candidates pre- vs. 18 375 post) without significant regional changes as did the number of transplants (7210 pre- vs. 8224 post). Waiting-list mortality improved from 12.2% to 8.1% (P < 0.001). Adjusted waiting-list mortality ratios remained geographically disparate. Region 10 and region 11 had lower hazard ratios (HR) but still had increased mortality (1.46, 95% confidence interval [CI] 1.34-1.60, P < 0.001; and HR 1.49, 95% CI 1.37-1.62, P < 0.001, respectively). Regions 3 and 6 had increased HR with persistently elevated waiting-list mortality (1.79, 95% CI 1.66-1.93, P < 0.001; and HR 1.29, 95% CI 1.16-1.45, P < 0.001, respectively). Model for End-state Liver Disease (MELD) exception continued to propagate a survival benefit (HR 0.65, 95% CI 0.63-0.68, P < 0.001). CONCLUSIONS: Although overall waiting-list mortality has decreased, geographic disparities persist, but appear reduced despite broader sharing policies enacted by Share35. The advantage afforded by MELD exception, while still present, was diminished by Share35 as organs are being shifted to MELD >35 candidates. The disparities highlighted by our findings imply a need to review current allocation policies to best balance local, regional, and national transplant environments.

Advanced non-alcoholic steatohepatitis cirrhosis: A high-risk population for pre-liver transplant portal vein thrombosis.

AIM: To examine if liver transplant recipients with high-risk non-alcoholic steatohepatitis (NASH) are at increased risk for pre-transplant portal venous thrombosis. METHODS: Data on all liver transplants in the United States from February 2002 through September 2014 were analyzed. Recipients were sorted into three distinct groups: High-risk (age > 60, body mass index > 30 kg/m2, hypertension and diabetes), low-risk and non-NASH cirrhosis. Multivariable logistic regression models were constructed. RESULTS: Thirty-five thousand and seventy-two candidates underwent liver transplantation and of those organ recipients, 465 were transplanted for high-risk and 2775 for low-risk NASH. Two thousand six hundred and twenty-six (7.5%) recipients had pre-transplant portal vein thrombosis; 66 (14.2%) of the high-risk NASH group had portal vein thrombosis vs 328 (11.8%) of the low-risk NASH group. In general, all NASH recipients were less likely to be male or African American and more likely to be obese. In adjusted multivariable regression analyses, high-risk recipients had the greatest risk of pre-transplant portal vein thrombosis with OR = 2.11 (95%CI: 1.60-2.76, P < 0.001) when referenced to the non-NASH group. CONCLUSION: Liver transplant candidates with high-risk NASH are at the greatest risk for portal vein thrombosis development prior to transplantation. These candidates may benefit from interventions to decrease their likelihood of clot formation and resultant downstream hepatic decompensating events. Prospective study is needed.

Liver transplant recipients with portal vein thrombosis receiving an organ from a high-risk donor are at an increased risk for graft loss due to hepatic artery thrombosis.

We hypothesize that recipients with pretransplant portal vein thrombosis (PVT) receiving organs from high-risk donors (HRD) are at an increased risk of HAT. Data on all liver transplants in the United States from February 2002 to March 2015 were analyzed. Recipients were sorted into two groups: those with PVT and those without. HRDs were defined by donor risk index (DRI) >1.7. Multivariable logistic regression models were constructed to assess the independent risk factors for HAT with the resultant graft loss ≤90 days from transplantation. A total of 60 404 candidates underwent liver transplantation; of those recipients, 623 (1.0%) had HAT, of which 66.0% (n = 411) received organs from HRDs compared with 49.3% (n = 29 473) in recipients without HAT (P < 0.001); 2250 (3.7%) recipients had pretransplantation PVT and received organs from HRDs. On adjusted multivariable analysis, PVT with a HRD organ was the most significant independent risk factor (OR 3.56, 95% CI 2.52-5.02, P < 0.001) for the development of HAT. Candidates with pretransplant PVT who receive an organ from a HRD are at the highest risk for postoperative HAT independent of other measurable factors. Recipients with pretransplant PVT would benefit from careful donor selection and possibly anticoagulation perioperatively.

Pre-transplant portal vein thrombosis is an independent risk factor for graft loss due to hepatic artery thrombosis in liver transplant recipients.

BACKGROUND: Hepatic artery thrombosis is an uncommon but catastrophic complication following liver transplantation. We hypothesize that recipients with portal vein thrombosis are at increased risk. METHODS: Data on all liver transplants in the U.S. during the MELD era through September 2014 were obtained from UNOS. Status one, multivisceral, living donor, re-transplants, pediatric recipients and donation after cardiac death were excluded. Logistic regression models were constructed for hepatic artery thrombosis with resultant graft loss within 90 days of transplantation. RESULTS: 63,182 recipients underwent transplantation; 662 (1.1%) recipients had early hepatic artery thrombosis; of those, 91 (13.8%) had pre-transplant portal vein thrombosis, versus 7.5% with portal vein thrombosis but no hepatic artery thrombosis (p < 0.0001). Portal vein thrombosis was associated with an increased independent risk of hepatic artery thrombosis (OR 2.17, 95% CI 1.71-2.76, p < 0.001) as was donor risk index (OR 2.02, 95% CI 1.65-2.48, p < 0.001). Heparin use at cross clamp, INR, and male donors were all significantly associated with lower risk. DISCUSSION: Pre-transplant portal vein thrombosis is associated with post-transplant hepatic artery thrombosis independent of other factors. Recipients with portal vein thrombosis might benefit from aggressive coagulation management and careful donor selection. More research is needed to determine causal mechanism.

Management of the Potential Organ Donor in the ICU: Society of Critical Care Medicine/American College of Chest Physicians/Association of Organ Procurement Organizations Consensus Statement.

This document was developed through the collaborative efforts of the Society of Critical Care Medicine, the American College of Chest Physicians, and the Association of Organ Procurement Organizations. Under the auspices of these societies, a multidisciplinary, multi-institutional task force was convened, incorporating expertise in critical care medicine, organ donor management, and transplantation. Members of the task force were divided into 13 subcommittees, each focused on one of the following general or organ-specific areas: death determination using neurologic criteria, donation after circulatory death determination, authorization process, general contraindications to donation, hemodynamic management, endocrine dysfunction and hormone replacement therapy, pediatric donor management, cardiac donation, lung donation, liver donation, kidney donation, small bowel donation, and pancreas donation. Subcommittees were charged with generating a series of management-related questions related to their topic. For each question, subcommittees provided a summary of relevant literature and specific recommendations. The specific recommendations were approved by all members of the task force and then assembled into a complete document. Because the available literature was overwhelmingly comprised of observational studies and case series, representing low-quality evidence, a decision was made that the document would assume the form of a consensus statement rather than a formally graded guideline. The goal of this document is to provide critical care practitioners with essential information and practical recommendations related to management of the potential organ donor, based on the available literature and expert consensus.

Increased risk of portal vein thrombosis in patients with cirrhosis due to nonalcoholic steatohepatitis.

Portal vein thrombosis (PVT) is a common complication of cirrhosis sometimes implicated in hepatic decompensation. There are no consistent epidemiologic data to suggest an increased risk of thrombotic complications in nonalcoholic steatohepatitis (NASH); however, research suggests an increased risk of thrombosis. Our aim was to examine the independent association between NASH cirrhosis and PVT in patients who underwent liver transplantation (LT) in a cross-sectional study. Data on all LTs occurring in the United States between January 1, 2003 and December 31, 2012 were obtained from the United Network for Organ Sharing. Multivariable models were constructed to assess the statistical associations and risk factors for the development of PVT. A total of 33,368 patients underwent transplantation. Of these, 2096 (6.3%) had PVT. Of the patients with PVT, 12.0% had NASH. When we compared these patients to a composite of all other causes of cirrhosis, an increased prevalence of PVT was again found, with 10.1% having PVT at the time of transplantation versus 6.0% without NASH (P < 0.001). The strongest risk factor independently associated with a diagnosis of PVT in a multivariable analysis was NASH cirrhosis (odds ratio, 1.55; 95% confidence interval, 1.33-1.81; P < 0.001). NASH cirrhosis appears to predispose a patient to PVT independently of other risk factors. These epidemiological findings provide support for the idea that NASH is a prothrombotic state, and they should lead to more research in treatment and prevention in this population.

Donation after circulatory determination of death: the university of michigan experience with extracorporeal support.

BACKGROUND: Extracorporeal support (ECS) during organ procurement from donors after circulatory determination of death (DCDD) could increase the number of donor organs and decrease posttransplant complications. This study reports the experience of a large transplant center with controlled DCDD. METHODS: A retrospective review of all potential controlled-DCDD cases between October 1, 2000 and July 31, 2013 was performed. We focused on methods, ethical and practical issues, and recipient outcome data of organs procured and transplanted in our institution using ECS-assisted DCDD (E-DCDD). RESULTS: ECS was used for organ procurement in 37 controlled DCDD. The number of organs procured per donor was 2.59, and the number of organs transplanted per donor was 1.68. Delayed graft function occurred in 31% of renal grafts. In three donors (8%), organ donation was not completed because of surgeon judgment. Forty-eight renal grafts (65.8%), thirteen livers (61.9%), and one pancreas (50%) were successfully transplanted. CONCLUSIONS: ECS can be routinely implemented in controlled DCDD. In our experience, the organs provided per donor was 2.59. Widely applied, EDCDD could result in more donor organs, especially when applied to DCDD in uncontrolled conditions.

A prospective, randomized trial of complete avoidance of steroids in liver transplantation with follow-up of over 7 years.

OBJECTIVES: Steroids are a mainstay of treatment in orthotopic liver transplantation (OLT) and are associated with significant morbidity. This trial was conducted to assess the efficacy of steroids avoidance. METHODS: Patients undergoing OLT between June 2002 and April 2005 were entered into a prospective, randomized trial of complete steroids avoidance and followed until November 2011. Recipients received either standard therapy (n = 50) or complete steroids avoidance (n = 50). Analyses were performed on an intention-to-treat basis. The mean follow-up of all recipients was 2095 ± 117 days. Sixteen (32%) recipients randomized to the steroids avoidance group ultimately received steroids for clinical indications. RESULTS: Incidences of diabetes and hypertension prior to or after OLT were similar in both groups, as was the incidence of rejection. Patient and graft survival rates at 1, 3 and 5 years were lower in the steroids avoidance group than in the standard therapy group (patient survival: 1-year, 80% versus 86%; 3-year, 68% versus 76%; 5-year, 60% versus 72%; graft survival: 1-year, 76% versus 76%; 3-year, 64% versus 74%; 5-year, 56% versus 72%), but the differences were not statistically different. CONCLUSIONS: Complete steroids avoidance provides liver transplant recipients with minimal benefit and appears to result in a concerning trend towards decreased graft and recipient survival. The present data support the use of at least a short course of steroids after liver transplantation.

Incidence and risk factors of hepatocellular carcinoma recurrence after liver transplantation in the MELD era.

BACKGROUND AND AIMS: Deceased donor liver transplantation (DDLT) rates for candidates with hepatocellular carcinoma (HCC) have significantly increased in the MELD era because of the extra priority given to these candidates. We examined the incidence and pre-DDLT radiological and donor factors associated with post-DDLT HCC recurrence in the MELD era. METHODS: Outcomes of HCC candidates aged ≥18 years that underwent DDLT between 2/28/02 and 6/30/08 (n = 94) were reviewed. The primary outcome was biopsy-proven post-LT HCC recurrence at any site. Kaplan-Meier analysis was used to calculate the cumulative incidence and Cox regression was used to identify the predictors of post-LT HCC recurrence. RESULTS: The median age of the 94 candidates who met the study criteria was 54 years, 64% had hepatitis C, median lab MELD was 13, and median pre-LT AFP was 47 ng/dl. Based upon pre-DDLT imaging, 94% candidates met the Milan criteria. The median waiting time to transplant was 47 days and 27% received pre-DDLT loco-regional therapy. Seventeen (18%) developed HCC recurrence after 2.1 median years with a cumulative incidence of 6.8, 12, and 19% at 1, 2, and 3 years post-DDLT. The pre-DDLT number of lesions (p = 0.015), largest lesion diameter (p = 0.008), and higher donor age (p = 0.002) were the significant predictors of HCC recurrence after adjusting for pre-LT loco-regional therapy and waiting time. Post-LT HCC recurrence (p < 0.0001) and higher donor age (p = 0.029) were associated with lower post-LT survival. CONCLUSIONS: Post-LT HCC recurrence is higher in our MELD era cohort than the reported rate of 8% at 4 years in Mazzaferro et al.'s study. The risk of HCC recurrence was significantly associated with the number of lesions and size of the largest lesion at the time of DDLT as well as with older donor age. Risk stratification using a predictive model for post-LT HCC recurrence based on pre-LT imaging and donor factors may help guide candidate selection and tailoring of HCC surveillance strategies after LT.

Patient decision making about organ quality in liver transplantation.

It is challenging to discuss the use of high-risk organs with patients, in part because of the lack of information about how patients view this topic. This study was designed to determine how patients think about organ quality and to test formats for risk communication. Semistructured interviews of 10 patients on the waiting list revealed limited understanding about the spectrum of organ quality and a reluctance to consider anything but the best organs. A computerized quantitative survey was then conducted with an interactive graph to elicit the risk of graft failure that patients would accept. Fifty-eight percent of the 95 wait-listed patients who completed the survey would accept only organs with a risk of graft failure of 25% or less at 3 years, whereas 18% would accept only organs with the lowest risk possible (19% at 3 years). Risk tolerance was increased when the organ quality was presented relative to average organs rather than the best organs and when feedback was provided about the implications for organ availability. More than three-quarters of the patients reported that they wanted an equal or dominant role in organ acceptance decisions. Men tended to prefer lower risk organs (mean acceptable risk = 29%) in comparison with women (mean acceptable risk = 35%, P = 0.04), but risk tolerance was not associated with other demographic or clinical characteristics (eg, the severity of liver disease). In summary, patients want to be involved in decisions about organ quality. Patients' risk tolerance varies widely, and their acceptance of high-risk organs can be facilitated if we present the risks of graft failure with respect to average organs and provide feedback about the implications for organ availability.

Value of delayed hypointensity and delayed enhancing rim in magnetic resonance imaging diagnosis of small hepatocellular carcinoma in the cirrhotic liver.

PURPOSE: To determine the diagnostic utility of delayed hypointensity and delayed enhancing rim on magnetic resonance imaging (MRI) as indicators of hepatocellular carcinoma (HCC) in arterially enhancing nodules < or =5 cm in the cirrhotic liver and determine the features that best predict HCC. MATERIALS AND METHODS: Gadolinium-enhanced MRI studies performed from January 2001 to December 2004 in patients with cirrhosis were evaluated for arterially enhancing nodules measuring < or =5 cm. Verification was via explant correlation, biopsy, or imaging follow-up. Sensitivity and specificity of diagnostic features of HCC were calculated. Features predictive of HCC were determined using the Generalized Estimating Equation approach. RESULTS: In all, 116 arterially enhancing nodules were identified in 80 patients (<2 cm: n = 79, 2-5 cm n = 37). Sensitivity and specificity of delayed hypointensity for HCC measuring < or =5 cm, 2-5 cm, and <2 cm were 0.54 (40 of 74) and 0.86 (36 of 42); 0.72 (23 of 32) and 0.80 (4 of 5); and 0.41 (17 of 42) and 0.87 (32 of 37). For the delayed enhancing rim sensitivity and specificity were 0.64 (47 of 74) and 0.86 (36 of 42); 0.75 (24 of 32) and 1.0 (5 of 5); and 0.55 (23 of 42) and 0.83 (31 of 37), respectively. Lesion size (> or =2 cm) and delayed enhancing rim, as main features and their interaction, were the most significant predictors of HCC. CONCLUSION: Delayed hypointensity and enhancing rim improve the specificity of diagnosis of HCC of all sizes but are seen less frequently in small (<2 cm) HCC. Nodule size (> or =2 cm) and delayed enhancing rim are the strongest predictors of HCC.