[D-Ala2, D-Leu5] Enkephalin Improves Liver Preservation During Normothermic Ex Vivo Perfusion.

BACKGROUND: Meeting the metabolic demands of donor livers using normothermic ex vivo liver perfusion (NEVLP) preservation technology is challenging. The delta opioid agonist [D-Ala2, D-Leu5] enkephalin (DADLE) has been reported to decrease the metabolic demand in models of ischemia and cold preservation. We evaluated the therapeutic potential of DADLE by investigating its ability to protect against oxidative stress and hepatic injury during normothermic perfusion. MATERIALS AND METHODS: Primary rat hepatocytes were used in an in vitro model of oxidative stress to determine the minimum dose of DADLE needed to induce protection and the mechanisms associated with protection. NEVLP was then used to induce injury in rat livers and determine the effectiveness of DADLE in preventing liver injury. RESULTS: In hepatocytes, DADLE was protective against oxidative stress and led to a decrease in phosphorylation of JNK and p38. Naltrindole, a δ-opioid receptor antagonist, blocked this effect. DADLE also activated the PI3K/Akt signaling pathway, and PI3K/Akt inhibition decreased the protective effects of DADLE treatment. In addition, DADLE treatment during NEVLP resulted in lower perfusate alanine aminotransferase and tissue malondialdehyde and better tissue adenosine triphosphate and glutathione. Furthermore, perfusion with DADLE compared with perfusate alone preserved tissue architecture. CONCLUSIONS: DADLE confers protection against oxidative stress in hepatocytes and during NEVLP. These data suggest that the mechanism of protection involved the prevention of mitochondrial dysfunction by opioid receptor signaling and subsequent increased expression of prosurvival/antiapoptotic signaling pathways. Altogether, data suggest that opioid receptor agonism may serve as therapeutic target for improved liver protection during NEVLP.

Outcomes of domino liver transplantation compared to deceased donor liver transplantation: a propensity-matching approach.

Domino liver transplantation (DLT) utilizes the explanted liver of one liver transplant recipient as a donor graft in another patient. While there may be unique risks associated with DLT, it is unclear if DLT has less favorable long-term outcomes than deceased donor liver transplantation (DDLT). We used a propensity score matching approach to compare the outcomes of DLT recipients to DDLT recipients. The United Network for Organ Sharing (UNOS) registry was queried for patients undergoing DLT or DDLT in 2002-2016. Each DLT recipient was matched to a unique DDLT recipient to compare mortality and graft failure. There were 126 DLT and 62 835 DDLT recipients meeting inclusion criteria. After propensity score matching on recipient pre-transplant characteristics, 123 DLT cases were matched to DDLT controls from the same UNOS region. On stratified Cox proportional hazards regression, DLT incurred no increase in the hazard of mortality [hazard ratio (HR) = 1.4; 95% confidence interval (CI): 0.8, 2.7; P = 0.265] or graft failure (HR = 1.2; 95% CI: 0.7, 2.1; P = 0.556) compared to DDLT. Using a large national registry, a propensity-matched analysis found no increased risk of mortality or graft failure associated with DLT compared to DDLT.

An early look at the Organ Procurement and Transplantation Network explant pathology form data.

In April 2012, the Organ Procurement and Transplantation Network (OPTN) implemented an online explant pathology form for recipients of liver transplantation who received additional wait-list priority for their diagnosis of hepatocellular carcinoma (HCC). The purpose of the form was to standardize the data being reported to the OPTN, which had been required since 2002 but were submitted to the OPTN in a variety of formats via facsimile. From April 2012 to December 2014, over 4500 explant forms were submitted, allowing for detailed analysis of the characteristics of the explanted livers. Data from the explant pathology forms were used to assess agreement with pretransplant imaging. Explant data were also used to assess the risk of recurrence. Of those with T2 priority, 55.7% were found to be stage T2 on explant. Extrahepatic spread (odds ratio [OR] = 6.8; P < 0.01), poor tumor differentiation (OR = 2.8; P < 0.01), microvascular invasion (OR = 2.6; P < 0.01), macrovascular invasion (OR = 3.2; P < 0.01), and whether the Milan stage based on the number and size of tumors on the explant form was T4 (OR = 2.4; P < 0.01) were the strongest predictors of recurrence. In conclusion, this analysis confirms earlier findings that showed an incomplete agreement between pretransplant imaging and posttransplant pathology in terms of HCC staging, though the number of patients with both no pretransplant treatment and no tumor in the explant was reduced from 20% to <1%. In addition, several factors were identified (eg, tumor burden, age, sex, region, ablative therapy, alpha-fetoprotein, Milan stage, vascular invasion, satellite lesions, etc.) that were predictive of HCC recurrence, allowing for more targeted surveillance of high-risk recipients. Continued evaluation of these data will help shape future guidelines or policy recommendations. Liver Transplantation 22 757-764 2016 AASLD.

Medicaid enrollment after liver transplantation: Effects of medicaid expansion.

Liver transplantation (LT) recipients in the United States have low rates of paid employment, making some eligible for Medicaid public health insurance after transplant. We test whether recent expansions of Medicaid eligibility increased Medicaid enrollment and insurance coverage in this population. Patients of ages 18-59 years receiving first-time LTs in 2009-2013 were identified in the United Network for Organ Sharing registry and stratified according to insurance at transplantation (private versus Medicaid/Medicare). Posttransplant insurance status was assessed through June 2015. Difference-in-difference multivariate competing-risks models stratified on state of residence estimated effects of Medicaid expansion on Medicaid enrollment or use of uninsured care after LT. Of 12,837 patients meeting inclusion criteria, 6554 (51%) lived in a state that expanded Medicaid eligibility. Medicaid participation after LT was more common in Medicaid-expansion states (25%) compared to nonexpansion states (19%; P < 0.001). Multivariate analysis of 7279 patients with private insurance at transplantation demonstrated that after the effective date of Medicaid expansion (January 1, 2014), the hazard of posttransplant Medicaid enrollment increased in states participating in Medicaid expansion (hazard ratio [HR] = 1.5; 95% confidence interval [CI] = 1.1-2.0; P = 0.01), but not in states opting out of Medicaid expansion (HR = 0.8; 95% CI = 0.5-1.3; P = 0.37), controlling for individual characteristics and time-invariant state-level factors. No effects of Medicaid expansion on the use of posttransplant uninsured care were found, regardless of private or government insurance status at transplantation. Medicaid expansion increased posttransplant Medicaid enrollment among patients who had private insurance at transplantation, but it did not improve overall access to health insurance among LT recipients. Liver Transplantation 22 1075-1084 2016 AASLD.

Conversion from twice daily tacrolimus capsules to once daily extended-release tacrolimus (LCP-Tacro): phase 2 trial of stable liver transplant recipients.

LCP-Tacro is an extended-release formulation of tacrolimus designed for once-daily dosing. Studies in renal transplantation demonstrate greater bioavailability with similar safety and efficacy vs. twice-daily tacrolimus capsules. In this phase 2 study, adult stable liver transplant patients on tacrolimus capsules (Prograf) twice-daily were converted to tacrolimus tablets (LCP-Tacro) once-daily; patients continued on LCP-Tacro once-daily for days 8-21; target trough levels were 5-15 ng/mL; 24-hour pharmacokinetic (PK) assessments were done on days 7 (baseline pre-switch), 14, and 21. A 6 month extension study phase evaluated PK and safety following a total of 52 weeks of LCP-Tacro. Fifty-seven patients completed LCP-Tacro dosing in the core study; 43 completed the extension phase. The mean conversion ratio was 0.71 (Prograf:LCP-Tacro). PK data demonstrated consistent exposure (AUC) at the lower conversion dose. Cmax , Cmax /Cmin ratio, percent fluctuation and swing were significantly (P<0.001) lower and Tmax significantly (P<0.001) longer for LCP-Tacro vs. Prograf. AUC24 and Cmin correlation coefficients after 7 and 14 days of therapy were ≥0.93. There were no significant differences in PK parameters at week 26 vs. 14. One patient experienced an unrelated serious adverse event (SAE) during the core study and discontinued. There were six unrelated SAEs in the extension and 1 possibly related (rejection) that resolved; there were 3 discontinuations due to AEs during the extension. In this study, patients were safely converted from Prograf twice-daily to LCP-Tacro. The greater bioavailability of LCP-Tacro allowed for once-daily dosing and similar (AUC) exposure at a dose approximately 30% less than the total daily dose of Prograf. LCP-Tacro displayed significantly lower peak and peak-trough fluctuations. LCP-Tacro administered over one year was well tolerated with no new safety concerns.

Orthotopic Kidney Transplant as a Fifth Intra-Abdominal Organ after Two Previous Kidney and Two Previous Pancreas Transplants.

Background: Patients with more than two prior kidney transplant procedures pose unique surgical challenges. Once both the right and left retroperitoneal spaces have been dissected, intra-abdominal implantation is usually necessary. If the external iliac arteries have been used previously, it is sometimes necessary to use the aorta and vena cava for implantation. Gaining safe exposure in these cases can be complicated by history of prior laparotomy, adhesive disease, and other surgical histories. Case Presentation. A 58-year-old female with type 1 diabetes and end-stage renal disease presented for surgical evaluation for kidney transplant. Surgical history was notable for prior simultaneous kidney-pancreas transplant followed by both a living donor kidney transplant and a pancreas after kidney transplant. She had undergone both an allograft nephrectomy and an allograft pancreatectomy and currently had a nonfunctioning kidney in the left retroperitoneal position and a nonfunctioning pancreatic allograft on the right common iliac artery. The entire distal aortoiliac system was surgically inaccessible. She was listed for transplantation, and a cadaveric graft was allocated. Intraoperatively, severe lower abdominal and pelvic adhesions prevented any use of the iliac system. A left native nephrectomy was performed, and the allograft was implanted in the left orthotopic position. The native left renal vein was used for outflow, the donor renal artery was joined end-to-side to the infrarenal aorta, and a uretero-ureterostomy was created. The operation was uneventful. The allograft functioned without delay, and almost one year later, the GFR is approximately 50 mg/dL. Conclusion: The left orthotopic position can be a good choice for kidney transplant candidates with histories of prior complex lower abdominal surgery.

Postoperative and Recurrent Hematuria after Pretransplant Core Needle Biopsy in Living Donor Kidney Transplant.

Background: Core needle and wedge biopsies are the two main pathologic ways to determine the suitability of a kidney allograft and to have a baseline allograft biopsy in case of future rejection. Case Presentation. A 57-year-old patient developed a renal arteriovenous fistula causing postoperative and recurrent hematuria after allograft pretransplant renal core needle biopsy and treated with selective Interventional radiology coil embolization. Conclusion: Delayed profound hematuria can be seen after pretransplant core needle renal biopsies and can recur again even after complete resolution, due to arteriovenous fistula formation in the renal calyceal system.

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.

Difference in Survival in Early Kidney after Liver Transplantation Compared with Simultaneous Liver-Kidney Transplantation: Evaluating the Potential of the "Safety Net".

BACKGROUND: Decisions on who requires simultaneous liver-kidney (SLK) transplantation are controversial. United Network for Organ Sharing implemented a "safety net" in 2017 providing prioritization on the kidney waitlist for patients with renal failure after liver transplantation. We aimed to compare survival after early kidney after liver transplantation (KALT) and SLK. STUDY DESIGN: We compared SLK, KALT, and liver transplantation alone (LTA) in adult patients who underwent deceased donor (DD) liver transplantation in the US, from 2002 to 2018. Early KALT was defined as 60 to 365 days between liver and subsequent kidney transplantation (reflecting safety net listing criteria). Patients who died within 60 days were excluded to mitigate immortal time bias favoring KALT. RESULTS: There were 6,774 SLK, 120 KALT at 60 to 365 days, and 11,501 LTA. Early KALT had equivalent survival compared with SLK, both for all KALT (hazard ratio [HR] 0.58, 95% CI 0.34-1.00, p = 0.05) and for DD KALT only (HR 0.72, 95% CI 0.37-1.38, p = 0.32). Simultaneous liver-kidney transplantation was associated with improved survival compared with LTA (HR 0.82. 95% CI 0.76-0.87, p < 0.01). Early KALT was associated with a greater reduction in mortality compared with LTA, but this was not significant (HR 0.58, 95% CI 0.39-1.00, p = 0.05). There was a lower proportion of early KALT in African Americans relative to SLK transplantations (7% vs 16%, p = 0.04). CONCLUSIONS: Early KALT has equivalent survival compared with SLK transplantation, both for all KALT and for DD KALT only, supporting the promise of the "safety net." There was a lower proportion of African-American patients undergoing early KALT, indicating the importance of monitoring access to early KALT under the "safety net" policy.

Immediate Postoperative Insulin Requirements May Predict Metabolic Outcome after Total Pancreatectomy and Islet Autotransplantation.

Chronic pancreatitis (CP) is a progressive disease that leads to eventual loss of endocrine and exocrine function. Total pancreatectomy and islet autotransplantation (TPIAT) is a treatment option for patients with CP; however, predicting postoperative metabolic outcomes remains elusive. In this single-center retrospective study, we report pre-TPIAT characteristics, beta cell function indices, islet yield, and post-TPIAT glucose management data to further understand their relationship. Islet yield, glucose level, and insulin requirement for 72 hours postoperatively were collected for a total of 13 TPIAT recipients between 9-2013 and 9-2018. In addition, their glucose control and basal insulin requirements at 3, 6, and 12 months post-TPIAT were analyzed. All 13 subjects had normal baseline fasting glucose levels. Median islet yield was 4882 IEq/kg (interquartile range 3412 to 8987). Median postoperative total insulin requirement on day 3 was 0.43 units/kg. Pre-TPIAT baseline glucose, insulin, or c-peptide level did not have a significant correlation with the islet yield. Similarly, there was no correlation between islet yield and insulin requirement at 72-hour postoperatively. However, there was an inverse correlation between the absolute islet yield (IEq) and insulin requirement at 6 months and 12 months following post-TPIAT. Further analysis of the relationship between 72-hour post-op insulin requirement and insulin requirement at discharge, 3, 6, and 12 months showed a positive correlation. Despite the finding of inverse correlation of islet yield with long-term basal insulin requirement, this study was not able to detect a correlation between the preoperative parameters to postoperative short-term or long-term outcome as noted in other studies. The 72-hour postoperative insulin requirement is a helpful postoperative predictor of patients needing long-term insulin management following TPIAT. This observation may identify a high-risk group of patients in need of more intensive diabetes education and insulin treatment prior to hospital discharge.

Factors influencing liver transplant length of stay at two large-volume transplant centers.

Length of stay (LOS) is considered a reliable surrogate for liver transplant resource utilization. Little information exists about how donor and recipient variables interact to affect transplant LOS. Data for adult, non-status 1 transplants (1998-2005), including the donor risk index (DRI) and Model for End-Stage Liver Disease (MELD) scores, were collected from 2 institutions (n = 745 for center A and n = 710 for center B). Cox proportional hazards models identified variables associated with LOS for the separate and combined cohorts. The cohorts differed significantly in donor, recipient, and transplant factors. DRI (1.46 for center A and 1.40 for center B, P = 0.0013) and MELD (22.4 for center A and 20.4 for center B, P = 0.046) were both higher at center A, but LOS was comparable (13.7 days for center A and 13.3 days for center B, P = 0.052). Three factors at center A (nonlocal donor, recipient age, and MELD) and 7 factors at center B (donor age and weight, recipient female gender, retransplant status, international normalized ratio, MELD, and cold ischemia time) were associated with transplant LOS. For the combined cohort, donor age, weight, nonlocal status, recipient age, female gender, retransplant status, MELD, and transplant center were LOS risk factors. In conclusion, the impact of donor and recipient variables on LOS varies by institution. However, the MELD score exerts a potent and consistent effect across institutions, emphasizing the dominant role of disease severity in liver transplant resource utilization.

Medicaid Participation among Liver Transplant Candidates after the Affordable Care Act Medicaid Expansion.

BACKGROUND: The 2014 Medicaid expansion in participating states increased insurance coverage among people with chronic health conditions, but its implications for access to surgical care remain unclear. We investigated how Medicaid expansion influenced the insurance status of candidates for liver transplantation (LT) and transplant center payor mix. STUDY DESIGN: Data on LT candidates aged 18 to 64 years, in 2012 to 2013 (pre-expansion) and 2014 to 2015 (post-expansion), were obtained from the United Network for Organ Sharing registry. Change between the 2 periods in the percent of LT candidates using Medicaid was compared between expansion and nonexpansion states. Multivariable logistic regression was used to determine how Medicaid expansion influenced individual LT candidates' likelihood of using Medicaid insurance. RESULTS: The study included 33,017 LT candidates, of whom 29,666 had complete data for multivariable analysis. Medicaid enrollment increased by 4% after Medicaid expansion in participating states. One-quarter of the transplant centers in these states experienced ≥10% increase in the proportion of LT candidates using Medicaid insurance. Multivariable analysis confirmed that Medicaid expansion was associated with increased odds of LT candidates using Medicaid insurance (odds ratio 1.49; 95% CI 1.34, 1.66; p < 0.001). However, the absolute number and demographic characteristics of patients listed for LT did not change in Medicaid expansion states during the post-expansion period. CONCLUSIONS: Candidates for LT became more likely to use Medicaid after the 2014 Medicaid expansion policy came into effect. Enactment of this policy did not appear to increase access to LT or address socioeconomic and demographic disparities in access to the LT wait list.

Severe, late-onset graft-versus-host disease in a liver transplant recipient documented by chimerism analysis.

A 52-year-old liver transplant recipient presented 8 months after transplantation with oral thrush, then 3 days later with oral ulcers and a diffuse rash, and 5 days later with an acutely reduced white blood cell count, rash, fever, and diarrhea. Bone marrow biopsy revealed severe aplasia. Although graft-versus-host disease (GVHD) was considered, the late onset of these symptoms was felt to render this etiology unlikely because GVHD usually occurs 2 to 6 weeks after transplantation. All potentially myelosuppressive medications were discontinued, and the patient was treated with high doses of hematopoietic growth factors. Because his symptoms continued, chimerism analysis was performed, which indicated that 96% of the peripheral blood mononuclear cells were of liver-donor origin. Ultimately, the patient underwent an allogeneic peripheral blood hematopoietic progenitor cell transplant from a human leukocyte antigen-identical brother, but he died 5 days after transplantation of overwhelming Candida kruseii infection. To our knowledge, this is the first chimerism-analysis-documented case of severe acute GVHD presenting so late after liver transplantation. It is of note that the patient had no known risks for GVHD in that he was relatively young and shared only one major human leukocyte antigen with his donor. Consideration should be given to GVHD as a cause of bone marrow aplasia at any time after organ transplantation. Storage of cell pellets from all transplant recipients and donors is highly recommended to facilitate the diagnostic evaluation.

High-grade microsteatosis and delay in hepatic function after orthotopic liver transplantation.

Macrovesicular steatosis may be used to exclude potential donor livers from use in transplantation. Livers with more than 50% macrovesicular steatosis are believed to be at risk for delayed graft function and primary graft nonfunction. However, the significance of even extensive microsteatosis is uncertain. The hematoxylin and eosin-stained slides of postperfusion donor liver biopsies from 161 transplants were examined. The type of steatosis (macrovesicular, low-grade microvesicular, and high-grade microvesicular ) was determined, and the extent of each type was semiquantitated into 3 groups (none, ≤50%, and >50%). These were analyzed in conjunction with the donor and recipient age and the recipient's sex and MELD score against postoperative outcome parameters, including serial measures of serum lactate, days in the intensive care unit and overall in hospital, and death less than 3 months posttransplant. High-grade microsteatosis usually coexisted with macrosteatosis and infrequently with low-grade microsteatosis. There was no significant association between the extent of either macrosteatosis or low-grade microsteatosis (even when >50%) and any of the outcome parameters. In contrast, the presence of high-grade microsteatosis was significantly associated with delayed hepatic function, but not with the other outcome parameters. Donor age greater than 60 years was associated with late postoperative rise in serum lactate, and higher recipient MELD score was associated with extended stay in the intensive care unit and in the hospital. In this patient population, the association of steatosis with adverse outcomes was largely restricted to delay in postoperative hepatic function, and was due to the subgroup that displayed high-grade microsteatosis.

Use of split-liver allografts does not impair pediatric recipient growth.

The use of split-liver (SL) allografts continues to be an excellent option for many pediatric recipients. Patient and graft survival with this graft type are comparable to patient and graft survival with whole organ grafts. Quality-of-life issues, specifically growth, for SL recipients have not been compared to those of recipients of more conventional whole-organ recipients. Pediatric recipients of SL and whole allografts at 2 institutions were identified. Height, z score, and delta z score were calculated for all recipients for each year after transplant. Between 1995 and 2004, 201 pediatric liver transplants were analyzed. Data were collected on 39 split-graft recipients and 36 whole-size recipients. Only subjects 3 years or younger were included in the study. Growth retardation was present in all recipients at transplant. Height z score post split and whole-size transplant were not statistically different at 1- (P = 0.65), 2- (P = 0.13), and 3-year (P = 0.32) anniversaries, respectively. Catch-up growth was present only in recipients of split grafts. In conclusion, the use of split grafts as opposed to whole-size grafts revealed no significant differences in terms of linear growth. Our report indicates that split-liver transplantation does not impair recipient growth.

Geographic disparities in deceased donor liver transplantation within a single UNOS region.

Although the Model for End-Stage Liver Disease (MELD) scoring system has improved the ability to measure medical urgency for transplantation, geographic disparities in the probability of being delisted as a result of complications of end-stage liver disease or death and in the probability of orthotopic liver transplantation (OLT) remain. The purpose of the current study was to identify factors associated with these variations among donor service areas (DSAs) in one United Network for Organ Sharing (UNOS) region. Data for 2,948 candidates listed for OLT within 4 DSAs in UNOS region 4 between February 2002 and November 2005 were obtained from UNOS. Multivariate regression models were used to identify study factors associated with delisting (due to deterioration or death) and likelihood of OLT. After risk adjustment for candidate characteristics, those listed in DSA-3 and DSA-4 were at significantly higher risk of delisting than candidates listed in DSA-2 (hazard ratio, 1.22 and 1.10 vs. 0.87 for DSA-2; P = 0.01 and 0.05, respectively). In addition, the likelihood of OLT was significantly higher for candidates listed in DSA-1 than in DSA-2, DSA-3 or DSA-4 (hazard ratio, 1.00 compared with 0.45, 0.77, and 0.51; P < 0.001 for all pairwise comparisons). Despite the implementation of the MELD system, great geographic disparities exist in the likelihood of delisting and for OLT, suggesting the need for further refinement in regional allocation strategies.

Corticosteroid-free immunosuppression with daclizumab in HCV(+) liver transplant recipients: 1-year interim results of the HCV-3 study.

This work is a 1-yr interim analysis of a prospective, randomized, multicenter trial evaluating the effect of corticosteroid-free immunosuppression on hepatitis C virus-positive (HCV(+)) liver transplant recipients following liver transplantation (LT). Patients received tacrolimus and corticosteroids (Arm 1; n = 80); tacrolimus, corticosteroids, and mycophenolate mofetil (MMF) (Arm 2; n = 79); or daclizumab induction, tacrolimus, and MMF (Arm 3; n = 153). At 1 yr, 64.1%, 63.4%, and 69.4% of patients achieved the composite primary endpoint of freedom from rejection, freedom from HCV recurrence, and freedom from treatment failure, respectively. Excellent patient and graft survival did not differ significantly among treatment arms. Freedom from HCV recurrence at 1 yr was 61.8 +/- 6.2%, 60.1 +/- 6.1%, and 67.0 +/- 4.3% in Arms 1, 2, and 3, respectively (P = not significant). Freedom from rejection was significantly higher in Arm 3 compared to Arm 1 (93.0 +/- 2.2% vs. 81.9 +/- 4.4%; P = 0.011). Multivariate analysis identified acute rejection (hazard ratio = 2.692; P = 0.001) and donor age (hazard ratio = 1.015; P = 0.001) as significant risk factors for HCV recurrence. HCV recurrence was not influenced by recipient demographics, HCV genotype, or immunosuppression. In conclusion, these results suggest that a corticosteroid-free regimen of tacrolimus and MMF following daclizumab induction is safe and effective in HCV(+) liver transplant recipients.