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Inpatient hypoglycemia (glucose ≤70 mg/dL) is a limitation of intensive control with insulin. Causes of hypoglycemia were evaluated in a randomized controlled trial examining intensive glycemic control (IG, target 140 mg/dL) versus moderate glycemic control (MG, target 180 mg/dL) on post-liver transplant outcomes.Hypoglycemic episodes were reviewed by a multidisciplinary team to calculate and identify contributing pathophysiologic and operational factors. A subsequent subgroup case control (1:1) analysis (with/without) hypoglycemia was completed to further delineate factors. A total of 164 participants were enrolled, and 155 patients were examined in depth.Overall, insulin-related hypoglycemia was experienced in 24 of 82 patients in IG (episodes: 20 drip, 36 subcutaneous [SQ]) and 4 of 82 in MG (episodes: 2 drip, 2 SQ). Most episodes occurred at night (41 of 60), with high insulin amounts (44 of 60), and during a protocol deviation (51 of 60). Compared to those without hypoglycemia (n = 127 vs. n = 28), hypoglycemic patients had significantly longer hospital stays (13.6 ± 12.6 days vs. 7.4 ± 6.1 days; P = .002), higher peak insulin drip rates (17.4 ± 10.3 U/h vs. 13.1 ± 9.9 U/h; P = .044), and higher peak insulin glargine doses (36.8 ± 21.4 U vs. 26.2 ± 24.3 U; P = .035). In the case-matched analysis (24 cases, 24 controls), those with insulin-related hypoglycemia had higher median peak insulin drip rates (17 U/h vs. 11 U/h; P = .04) and protocol deviations (92% vs. 50%; P = .004).Peak insulin requirements and protocol deviations were correlated with hypoglycemia.DM = diabetes mellitus ICU = intensive care unit IG = intensive glycemic control MELD = Model for End-stage Liver Disease MG = moderate glycemic control SQ = subcutaneous.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver injury worldwide. NAFLD is composed of a spectrum of histologically defined stages of liver injury ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), in which inflammation and hepatocellular injury can ultimately lead to fibrosis, cirrhosis, and hepatocellular carcinoma. NASH is currently the most common indication for liver transplantation (LT) in women and adults over the age of 65 and is on pace to become the most common indication for LT overall in the wake of rising rates of metabolic syndrome and declining rates of hepatitis C virus.1,2 With survival rates increasing in the LT population, allograft-associated NAFLD is likely to impact an increasing number of LT recipients in the future. Studies have demonstrated evidence of recurrent or de novo hepatic steatosis in 10%–100%, and NASH in up to 36% of patients at 3–5 y post-LT.3-6 Despite high rates of NAFLD recurrence, a paucity of diagnostic tools are available for reliable diagnosis and serial monitoring. Even more so than NASH before transplant, the development of post-LT NASH and its progression to advanced fibrosis can occur without concomitant liver enzyme abnormalities in the posttransplant setting.7 High rates of recurrence in patients transplanted for NASH cirrhosis are linked to baseline metabolic dysregulation exacerbated by the additive impact of immunosuppressive agents. Although liver enzymes may not reliably indicate allograft disease, the abnormal metabolic milieu can be reflected in altered blood metabolite profiles, which may facilitate the identification of recipients with or at high risk for recurrent NASH. Currently, noninvasive detection of allograft NAFLD is limited to the identification of steatosis on liver imaging, although liver biopsy is needed to differentiate NAFL from NASH, identify the presence of mild to moderate fibrosis, and differentiate NAFLD from most other causes of liver dysfunction. Liver biopsy has drawbacks that limit routine utilization, such as invasiveness, cost, and susceptibility to sampling error or interpretation variability.8,9 For these reasons, liver biopsy is neither a feasible nor desirable option for screening or for serial monitoring in most patients at risk for recurrent NASH. Imaging modalities such as transient elastography (TE) are widely used in the nontransplant setting to identify advanced fibrosis, although TE has limited accuracy in diagnosing NASH or lesser degrees of fibrosis.10 In the LT population, the accuracy of TE to characterize disease recurrence, especially NAFLD, is even more limited.11 Biomarker panels, including metabolites, proteins, and nucleic acids, are all being investigated as a supplement to or replacement for liver biopsy. Current panels used to detect NAFLD are generally derived from direct and indirect measures of steatosis (eg, Fatty Liver Index and SteatoTest), NASH (eg, NASH test and OWLiver), fibrosis (eg, FIB-4 index, NAFLD fibrosis score, FibroTest, and ELF), or some combination of the above. These biomarker panels have shown promise in the nontransplant setting, although none have been validated for use in post-LT allograft-associated NAFLD.12-18 Little is known about whether NASH in the posttransplant state has a unique biomarker signature because of altered metabolism from immunosuppressive agents, native graft disease, and increased insulin resistance.19 The aim of this novel exploratory study was to use an unbiased metabolomics approach to identify candidate metabolites capable of differentiating NAFLD from normal liver (NL) and other causes of liver dysfunction following LT. Once identified, future validation and confirmatory studies could lead to a biomarker panel for noninvasive monitoring of NAFLD recurrence.

With improving surgical technique and perioperative care, liver transplant recipients will continue to survive longer and longer. After the first year of transplantation, the risk of mortality is largely based on the development of renal disease and metabolic syndrome, including hypertension, hyperlipidemia, diabetes, and obesity. Mechanistically, these complications can be a result of immunosuppressive medications as well as a return to poor dietary and exercise regimens posttransplant. Renal injury is almost exclusively a result of calcineurin toxicity over time, and new strategies are in place, utilizing mammalian target of rapamycin inhibitors to minimize this risk. Cardiovascular complications can also be spurred on by immunosuppressive medications, and close monitoring and treatment with standard agents are required in the recipient. Diabetes is perhaps the most feared medical complication posttransplant, as it carries a higher risk of mortality. It is also impacted by many of the different immunosuppressive regimens. Finally, novel strategies are being researched to appropriately treat the obese patient pre- and post liver transplant. This review contains 1 figure, 2 tables, and 52 references. Key Words: complications, diabetes, everolimus, immunosuppression, liver transplant, medical, metabolic syndrome, obesity, posttransplant, renal disease, tacrolimus.

BACKGROUND In the general population, even mild renal disease is associated with increased cardiovascular (CV) complications. Whether this is true in liver transplant recipients (LTR) is unknown. METHODS This was a retrospective cohort study of 671 LTR (2002-2012) from a large urban tertiary care center and 37 322 LTR using Vizient hospitalization data linked to the United Network for Organ Sharing. The 4-variable Modification of Diet in Renal Disease equation estimated glomerular filtration rate (eGFR). Outcomes were 1-year CV complications (death/hospitalization from myocardial infarction, heart failure, atrial fibrillation, cardiac arrest, pulmonary embolism, or stroke) and mortality. Latent mixture modeling identified trajectories in eGFR in the first liver transplantation (LT) year in the 671 patients. RESULTS Mean (SD) eGFR was 72.1 (45.7) mL/min per 1.73 m. Six distinct eGFR trajectories were identified in the local cohort (n = 671): qualitatively normal-slow decrease (4% of cohort), normal-rapid decrease (4%), mild-stable (18%), mild-slow decrease (35%), moderate-stable (30%), and severe-stable (9%). In multivariable analyses adjusted for confounders and baseline eGFR, the greatest odds of 1-year CV complications were in the normal-rapid decrease group (odds ratio, 10.6; 95% confidence interval, 3.0-36.9). Among the national cohort, each 5-unit lower eGFR at LT was associated with a 2% and 5% higher hazard of all-cause and CV-mortality, respectively (P < 0.0001), independent of multiple confounders. CONCLUSIONS Even mild renal disease at the time of LT is a risk factor for posttransplant all-cause and CV mortality. More rapid declines in eGFR soon after LT correlate with risk of adverse CV outcomes, highlighting the need to study whether early renal preservation interventions also reduce CV complications.

Estimation of glomerular filtration rate (eGFR) in patients with liver disease is suboptimal in the presence of renal dysfunction. We developed a model for GFR assessment in liver disease (GRAIL) before and after liver transplantation (LT). GRAIL was derived using objective variables (creatinine, blood urea nitrogen, age, gender, race, and albumin) to estimate GFR based on timing of measurement relative to LT and degree of renal dysfunction (www.bswh.md/grail). The measured GFR (mGFR) by iothalamate clearance (n = 12,122, 1985-2015) at protocol time points before/after LT was used as reference. GRAIL was compared with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD-4, MDRD-6) equations for mGFR < 30 mL/min/1.73 m2 . Prediction of development of chronic kidney disease (mGFR < 20 mL/min/1.73 m2 , initiation of chronic dialysis) and listing or receipt of kidney transplantation within 5 years was examined in internal cohort (n = 785) and external validation (n = 68,217, 2001-2015). GRAIL had less bias and was more accurate and precise as compared with CKD-EPI, MDRD-4, and MDRD-6 at time points before/after LT for low GFR. For mGFR < 30 mL/min/1.73 m2 , the median difference (eGFR-mGFR) was GRAIL: 5.24 (9.65) mL/min/1.73 m2 as compared with CKD-EPI: 8.70 (18.24) mL/min/1.73 m2 , MDRD-4: 8.82 (17.38) mL/min/1.73 m2 , and MDRD-6: 6.53 (14.42) mL/min/1.73 m2 . Before LT, GRAIL correctly classified 75% as having mGFR < 30 mL/min/1.73 m2 versus 36.1% (CKD-EPI), 36.1% (MDRD-4), and 52.8% (MDRD-6) (P < 0.01). An eGFR < 30 mL/min/1.73 m2 by GRAIL predicted development of CKD (26.9% versus 4.6% CKD-EPI, 5.9% MDRD-4, and 10.5% MDRD-6) in center data and needing kidney after LT (48.3% versus 22.0% CKD-EPI versus 23.1% MDRD-4 versus 48.3% MDRD-6, P < 0.01) in national data within 5 years after LT. Conclusion: GRAIL may serve as an alternative model to estimate GFR among patients with liver disease before and after LT at low GFR.

Strategies are needed to reduce waitlist mortality and increase transplantation rates. Advances in hepatitis C therapy has allowed the transplant community to look toward utilization of grafts from hepatitis C viremic donors to expand the organ pool. Use of such grafts for hepatitis C-negative patients is being evaluated and debated, and early trial data are emerging.Both hepatitis C antibody-positive/nucleic acid test-negative and viremic donors are currently underutilized. Outcomes for viral hepatitis C (HCV) viremic transplant recipients are improving in the setting of direct-acting antiviral therapy. Optimization of graft utilization from HCV 'positive' donors and expansion to use of viremic donors for HCV-negative recipients will likely reduce waitlist mortality and result in net overall reduction in healthcare expenditures.Herein, we provide a review of recent advancements relating to hepatitis C in solid organ transplant and outline future directions. A primary future focus will be data collection of outcomes of transplantation of grafts from HCV 'viremic' donors to nonviremic recipients in formal clinical trial protocols.

The transition of young adults (YA) from paediatric to adult health services is a challenging time for patients, parents / care providers and health care professionals. This period has a higher prevalence of mental health problems and is associated with high rates of non-adherence.[1][1] These

In the context of organ shortage, the opioid epidemic, and effective direct-acting antiviral (DAA) therapy for hepatitis C (HCV), more HCV-infected donor organs may be used for liver transplantation. Current data regarding outcomes after donor-derived HCV in previously non-viremic liver transplant recipients are limited. Clinical data for adult liver transplant recipients with donor-derived HCV infection from March 2017 to January 2018 at our institution were extracted from the medical record. Ten patients received livers from donors known to be infected with HCV based on positive nucleic acid testing (NAT). Seven had a prior diagnosis of HCV and were treated before liver transplantation. All recipients were non-viremic at the time of transplantation. All 10 recipients derived hepatitis C infection from their donor and achieved sustained virologic response at 12 weeks post-treatment (SVR-12) with DAA-based regimens, with a median time from transplant to treatment initiation of 43 days (IQR 20–59). There have been no instances of graft loss or death, with median follow-up of 380 days (IQR 263–434) post-transplant. Transplantation of HCV-viremic livers into non-viremic recipients results in acceptable short-term outcomes. Such strategies may be used to expand the donor pool and increase access to liver transplantation.

The 2014 Annual Meeting of the International Liver Transplantation Society was held in London, England. This was the 20th meeting of the Society and was marked by a joint meeting including the European Liver and Intestinal Association as well as the Liver Intensive Care Group of Europe. The meeting included symposia, invited lectures, debates, oral presentations, and posters. The principal themes were living donation, expanding the deceased donor pool, machine preservation, and new oral therapies for hepatitis C virus. This report highlights the scientific discussions of this meeting. Liver Transpl 21:991-1000, 2015. © 2015 AASLD.

Use of organs from donors testing positive for hepatitis B virus (HBV) may safely expand the donor pool. The American Society of Transplantation convened a multidisciplinary expert panel that reviewed the existing literature and developed consensus recommendations for recipient management following the use of organs from HBV positive donors. Transmission risk is highest with liver donors and significantly lower with non-liver (kidney and thoracic) donors. Antiviral prophylaxis significantly reduces the rate of transmission to liver recipients from isolated HBV core antibody positive (anti-HBc+) donors. Organs from anti-HBc+ donors should be considered for all adult transplant candidates after an individualized assessment of the risks and benefits and appropriate patient consent. Indefinite antiviral prophylaxis is recommended in liver recipients with no immunity or vaccine immunity but not in liver recipients with natural immunity. Antiviral prophylaxis may be considered for up to 1 year in susceptible non-liver recipients but is not recommended in immune non-liver recipients. Although no longer the treatment of choice in patients with chronic HBV, lamivudine remains the most cost-effective choice for prophylaxis in this setting. Hepatitis B immunoglobulin is not recommended.

Background Increasing use of kidney grafts for simultaneous liver and kidney (SLK) transplants is causing concern about the most effective utilization of scarce kidney graft resources. This study evaluated the impact of implementing the proposed United Network for Organ Sharing SLK transplant policy on outcomes for end-stage liver disease (ESLD) and end-stage renal disease (ESRD) patients awaiting transplant. Methods A Markov model was constructed to simulate a hypothetical cohort of ESLD patients over a 30-year time horizon starting from age 50. The model applies the different criteria being considered in the United Network for Organ Sharing policy and tallies outcomes, including numbers of procedures and life years after liver transplant alone (LTA) or SLK transplant. Results When 1-week pretransplant dialysis duration is required, the numbers of SLK transplants and LTAs would be 648 and 9,065, respectively. If the pretransplant dialysis duration is extended to 12 weeks, there would be 240 SLK transplants and 9,426 LTAs. This change results in a decrease of 6,483 life years among SLK transplant recipients and an increase of 4,971 life years among LTA recipients. However, by increasing the dialysis duration to 12 weeks from 1 week, 408 kidney grafts would be released to the kidney waitlist because of the decline in SLK transplants; this yields 796 additional life years gained among ESRD patients. Conclusion Implementation of the proposed SLK transplant policy could restore access to kidney transplants for patients with ESRD albeit at the detriment of patients with ESLD and renal impairment.

Cardiovascular disease (CVD) complications are important causes of morbidity and mortality after orthotopic liver transplantation (OLT). There is currently no preoperative risk assessment tool that allows physicians to estimate the risk for CVD events following OLT. We sought to develop a point-based prediction model (risk score) for CVD complications after OLT, the CAR-OLT risk score, among a cohort of 1024 consecutive patients aged 18-75 years who underwent first OLT in a tertiary-care teaching hospital (2002-2011). The main outcome measures were major 1-year CVD complications, defined as death from a CVD cause or hospitalization for a major CVD event (myocardial infarction, revascularization, heart failure, atrial fibrillation, cardiac arrest, pulmonary embolism, and/or stroke). The bootstrap method yielded bias-corrected 95% confidence intervals for the regression coefficients of the final model.Among 1024 first OLT recipients, major CVD complications occurred in 329 (32.1%). Variables selected for inclusion in the model (using model optimization strategies) included pre-operative recipient age, sex, race, employment status, education status, history of hepatocellular carcinoma, diabetes, heart failure, atrial fibrillation, pulmonary or systemic hypertension, and respiratory failure. The discriminative performance of the CAR-OLT point-based score (C statistic=0.78, bias-corrected C statistic=0.77) was superior to other published risk models for postoperative CVD morbidity and mortality, and it had appropriate calibration (Hosmer-Lemeshow p=0.33). Conclusion: The point-based CAR-OLT risk score can identify patients at risk for CVD complications after OLT surgery (available at: www.carolt.us). This score may be useful for identification of candidates for further risk stratification or other management strategies to improve CVD outcomes after OLT. This article is protected by copyright. All rights reserved.

While advances in immunosuppressive therapy have lowered the rate of acute rejection following liver transplantation, the consequence has been an increase in morbidity and mortality related to the lifelong need for maintenance immunosuppression. These complications include an increased risk of malignancy, infection, metabolic disorders, and chronic kidney disease, as well as high health care costs associated with these therapies and the required drug monitoring. Given these issues, most clinicians attempt trial and error dose minimization with variable success rates, and there has been significant interest in full drug withdrawal in select patients through research protocols. These strategies would be more successful if immunomodulatory therapies early after transplantation could be developed and if immune activation biomarkers guiding drug tapering were available to personalize these approaches. This review will review the mechanisms of liver transplant tolerance and potential strategies to achieve immunosuppression withdrawal.

Nonmyeloablative conditioning followed by donor bone marrow infusion (BMI) to induce tolerance has not been robustly tested in liver transplantation (LT) and may be unsafe at the time of LT. We hypothesized T cell-depleted BMI is effective in inducing tolerance when delayed after LT, resulting in potentially safer future clinical applications.Nonimmunosuppressed syngeneic (Lewis to Lewis) and allogeneic (ACI to Lewis) rat LT transplants were initially performed as controls. Three experimental allogeneic LT groups were treated with tacrolimus (TAC) for 3 to 4 weeks and then underwent: (1) TAC withdrawal alone; (2) nonmyeloablative conditioning (anti-αβTCR mAb + total body irradiation [300 cGy]) followed by TAC withdrawal; (3) Nonmyeloablative conditioning + donor BMI (100 × 10 T cell-depleted bone marrow cells) followed by TAC withdrawal.All group 1 recipients developed chronic rejection. Group 2 had long-term survival but impaired liver function and high donor-specific antibody (DSA) levels. In contrast, group 3 (conditioning + BMI) had long-term TAC-free survival with preserved liver function and histology, high mixed chimerism and blood/liver/spleen CD4 + CD25 + Foxp3+ regulatory T cells, and low DSA titers, similar to syngeneic grafts. While donor-specific tolerance was observed post-BMI, graft-versus-host disease was not.These results support that donor-specific tolerance can be achieved with BMI even when delayed after LT and this tolerance correlates with increased mixed chimerism, regulatory T cell generation, and diminished DSA.

Colorectal cancer (CRC) is a common malignancy worldwide. Some studies suggest that organ recipients are at a higher risk for CRC than the general population. The underlying transplant indications and their inherent risk factors for CRC may drive the variation in incidence rates that are seen in patients receiving different allografts. Recipients with cystic fibrosis are now recognized as a population at high risk for CRC at a young age. Transplant recipients have high mortality following a CRC diagnosis, even if it is detected at an early stage. Certain types of immunosuppression have been shown to accelerate cancer transformation and may contribute to the more aggressive phenotype seen in organ recipients. Given the high incidence and progressive nature of posttransplant CRC, shorter screening intervals with a modality that can detect early-stage polyps may be essential to prevent mortality. Future research is needed to better elucidate the role of immunosuppression in carcinogenesis. This comprehensive review examines CRC risk, screening, and management specific to organ transplant candidates and recipients.

Cardiovascular disease (CVD) contributes to excessive long-term mortality after liver transplantation (LT); however, little is known about early postoperative CVD mortality in the current era. In addition, there is no model for predicting early postoperative CVD mortality across centers. We analyzed adult recipients of primary LT in the Organ Procurement and Transplantation Network (OPTN) database between February 2002 and December 2012 to assess the prevalence and predictors of early (30-day) CVD mortality, which was defined as death from arrhythmia, heart failure, myocardial infarction, cardiac arrest, thromboembolism, and/or stroke. We performed logistic regression with stepwise selection to develop a predictive model of early CVD mortality. Sex and center volume were forced into the final model, which was validated with bootstrapping techniques. Among 54,697 LT recipients, there were 1576 deaths (2.9%) within 30 days. CVD death was the leading cause of 30-day mortality (40.2%), and it was followed by infection (27.9%) and graft failure (12.2%). In a multivariate analysis, 9 significant covariates (6 recipient covariates, 2 donor covariates, and 1 operative covariate) were identified: age, preoperative hospitalization, intensive care unit status, ventilator status, calculated Model for End-Stage Liver Disease score, portal vein thrombosis, national organ sharing, donor body mass index, and cold ischemia time. The model showed moderate discrimination (C statistic = 0.66, 95% confidence interval = 0.63-0.68). In conclusion, we provide the first multicenter prognostic model for the prediction of early post-LT CVD death, the most common cause of early post-LT mortality in the current transplant era. However, evaluations of additional CVD-related variables not collected by the OPTN are needed in order to improve the model's accuracy and potential clinical utility.

There are complex risk-benefit tradeoffs with different transplantation strategies for end-stage liver disease patients on renal support. Using a Markov discrete-time state transition model, we compared survival for this group with 3 strategies: simultaneous liver-kidney (SLK) transplantation, liver transplantation alone (LTA) followed by immediate kidney transplantation if renal function did not recover, and LTA followed by placement on the kidney transplant wait list. Patients were followed for 30 years from the age of 50 years. The probabilities of events were synthesized from population data and clinical trials according to Model for End-Stage Liver Disease (MELD) scores (21-30 and >30) to estimate input parameters. Sensitivity analyses tested the impact of uncertainty on survival. Overall, the highest survival rates were seen with SLK transplantation for both MELD score groups (82.8% for MELD scores of 21-30 and 82.5% for MELD scores > 30 at 1 year), albeit at the cost of using kidneys that might not be needed. Liver transplantation followed by kidney transplantation led to higher survival rates (77.3% and 76.4%, respectively, at 1 year) than placement on the kidney transplant wait list (75.1% and 74.3%, respectively, at 1 year). When uncertainty was considered, the results indicated that the waiting time and renal recovery affected conclusions about survival after SLK transplantation and liver transplantation, respectively. The subgroups with the longest durations of pretransplant renal replacement therapy and highest MELD scores had the largest absolute increases in survival with SLK transplantation versus sequential transplantation. In conclusion, the findings demonstrate the inherent tension in choices about the use of available kidneys and suggest that performing liver transplantation and using renal transplantation only for those who fail to recover their native renal function could free up available donor kidneys. These results could inform discussions about transplantation policy. Liver Transpl 20:1034-1044, 2014. © 2014 AASLD.

The International Liver Transplantation Society held its annual meeting from June 12 to 15 in Sydney, Australia. More than 800 registrants attended the congress, which opened with a conference celebrating 50 years of liver transplantation (LT). The program included series of featured symposia, focused topic sessions, and oral and poster presentations. This report is by no means all-inclusive and focuses on specific abstracts on key topics in LT. Similarly to previous reports, this one presents data in the context of the published literature and highlights the current direction of LT. Liver Transpl 20:7–14, 2014. © 2013 AASLD.

We report a 43-year-old man who presented for evaluation of ascites, varices, and hepatosplenomegaly. Initial labs were notable for normal platelets, mild liver synthetic dysfunction, and disproportionately elevated alkaline phosphatase. He was presumed to have underlying cirrhosis, and diuresis was attempted without success. A transjugular liver biopsy showed marked sinusoidal dilation without cirrhosis. Diagnostic paracentesis revealed fluid studies suggestive of cardiac ascites. Further cardiac evaluation confirmed constrictive pericarditis. The case highlights the importance of considering a broad differential in the evaluation of ascites.

Traditionally, chronic calcineurin inhibitor (CNI) nephrotoxicity has been considered to be one of the main nonimmune mechanisms causing chronic renal allograft dysfunction. CNI minimization and withdrawal strategies have yielded inconsistent results. Few studies address the feasibility of CNI elimination in a prednisone-free regimen. We report a prospective, randomized trial in 200 patients evaluating the impact on renal function and incidence of acute rejection after conversion from tacrolimus (Tac) to sirolimus (SRL). Patients with recent (3 months) acute rejection episodes or with0.5 g/day of proteinuria were excluded. All were induced with alemtuzumab, underwent rapid steroid elimination and were maintained on mycophenolate mofetil and Tac. At 12 months posttransplant, patients were randomized 2:1 to SRL (n = 123) or maintained on Tac (n = 64). Mean follow-up was 41.1 ± 15.8 months in the SRL group and 40.7 ± 14.4 months in the Tac group. Biopsy-proven acute rejection at 24 months postrandomization was similar between the groups. Patient survival, graft survival and estimated GFR were also not statistically different. Our study demonstrates that in a prednisone-free immunosuppressive regimen, conversion from Tac to SRL at 12 months posttransplantation is not associated with increased rates of acute rejection and graft loss. However, despite CNI elimination, renal allograft function is equally maintained in both groups.

In this article the medications that have been shown to increase rates of drug-induced liver injury in patients with cirrhosis and the important drug-drug interactions in recipients of liver transplantation are reviewed. In general, the risk of drug-induced liver injury in patients with cirrhosis does not seem to be higher when compared with the noncirrhotic population. There are, however, 2 classes of agents that have been implicated-medications used to treat tuberculosis and medications used to treat human immunodeficiency virus infection. However, with careful monitoring, even significant interactions can be effectively managed.

BACKGROUND It is unclear if new costimulatory blockade agents, such as the cytotoxic T lymphocyte-associated antigen 4-Ig molecule belatacept (BEL), promote or inhibit the potential for immunologic tolerance in transplantation. We therefore tested the in vitro effects of BEL on human regulatory T cells (Tregs) in mixed lymphocyte reactions (MLR) alone and in combination with maintenance agents used in transplant recipients. METHODS BEL, mycophenolic acid (MPA), and sirolimus, either alone or in combination, were added to healthy volunteer Treg-MLR, testing (a) H-TdR incorporation for inhibition of lymphoproliferation and (b) flow cytometry to analyze for newly generated CD4+ CD25(high) FOXP3+ Tregs in carboxyfluorescein succinimidyl ester-labeled MLR responders. In addition, the modulatory effects of putative Tregs generated in the presence of these drugs were also tested using the lymphoproliferation and flow cytometric assays. RESULTS In comparison with medium controls, BEL dose-dependently inhibited both lymphoproliferation and Treg generation in human leukocyte antigen DR matched and mismatched MLRs either alone or in combination with MPA or sirolimus. However, MPA alone inhibited lymphoproliferation but significantly enhanced Treg generation at subtherapeutic concentrations (P

Maintenance of cardiac function is critical to the survival of patients with end-stage liver disease after liver transplantation (LT). We sought to determine whether pre-LT echocardiographic indices of right heart structure and function were independently predictive of morbidity and mortality post-LT. We retrospectively studied 216 consecutive patients who underwent pre-LT 2-dimensional/Doppler echocardiography with subsequent LT from 2007 to 2010. A blinded reader analyzed multiple echocardiographic parameters, including right ventricular structure and function, pulmonary artery systolic pressure (PASP) and the presence and severity of tricuspid regurgitation (TR). On univariate analysis, Model of End-Stage Liver Disease (MELD) score, PASP, presence of ≥mild TR, post–operative renal replacement therapy (RRT) and spontaneous bacterial peritonitis were found to be significant predictors of adverse outcomes. On multivariate analysis, only ≥mild TR was found to predict both patient mortality (p = 0.0024, HR = 3.91, 95% CI: 1.62–9.44) and graft failure (p = 0.0010, HR = 3.70, 95% CI: 1.70–8.06). PASP and MELD correlated with post-LT intensive care unit length of stay (LOS) and, along with hemodialysis, were associated with hospital LOS and time on ventilator. In conclusion, pre-LT echocardiographic assessments of the right heart may be useful in predicting post-LT morbidity and mortality and guiding the selection of appropriate LT candidates.

The ability to achieve immunologic tolerance after transplantation is a therapeutic goal. Here, we report interim results from an ongoing trial of tolerance in HLA-identical sibling renal transplantation. The immunosuppressive regimen included alemtuzumab induction, donor hematopoietic stem cells, tacrolimus/mycophenolate immunosuppression converted to sirolimus, and complete drug withdrawal by 24 months post-transplantation. Recipients were considered tolerant if they had normal biopsies and renal function after an additional 12 months without immunosuppression. Of the 20 recipients enrolled, 10 had at least 36 months of follow-up after transplantation. Five of these 10 recipients had immunosuppression successfully withdrawn for 16-36 months (tolerant), 2 had disease recurrence, and 3 had subclinical rejection in protocol biopsies (nontolerant). Microchimerism disappeared after 1 year, and CD4(+)CD25(high)CD127(-)FOXP3(+) regulatory T cells and CD19(+)IgD/M(+)CD27(-) B cells were increased through 5 years post-transplantation in both tolerant and nontolerant recipients. Immune/inflammatory gene expression pathways in the peripheral blood and urine, however, were differentially downregulated between tolerant and nontolerant recipients. In summary, interim results from this trial of tolerance in HLA-identical renal transplantation suggest that predictive genomic biomarkers, but not immunoregulatory phenotyping, may be able to discriminate tolerant from nontolerant patients.

Candidate selection for liver transplantation presents challenging ethical issues that require balancing the principles of justice and utility. The goal of this study was to assess the opinions of U.S. transplant providers regarding the ways in which controversial medical and psychosocial characteristics influence patient eligibility for liver transplantation. An online, anonymous survey about adult patient characteristics was sent to providers (hepatologists, surgeons, psychiatrists, and social workers) at all 102 active adult liver transplant centers in the United States. A majority of the providers (251/444 or 56.5%) completed the survey. The providers were queried about 8 characteristics, and the 3 that were ranked most controversial were incarceration, marijuana use, and psychiatric diagnoses. Most providers identified a patient age ≥ 80 years (62.7%), a body mass index ≥ 45 kg/m2 (56.6%), and current incarceration with a lifetime sentence (54.7%) as absolute contraindications to liver transplantation. In a multivariate analysis, the identification of absolute contraindications varied significantly with the provider type, the center volume, and the geographical region. Less than half of the providers reported that their centers had written policies regarding most of the characteristics examined. In conclusion, providers differ significantly in their opinions on controversial patient characteristics and transplant contraindications. Along with a paucity of literature data on outcomes, these provider differences may play a role in the fact that many centers do not have formal policies for selecting patients with these characteristics. Evidence-based data on the outcomes of such patients are needed to guide the formation of written policies to better standardize eligibility criteria.

From May 16–19, 2012, the International Liver Transplantation Society held its annual congress in San Francisco, CA. More than 1300 registrants attended the meeting, which included a premeeting conference entitled Balancing Risk in Liver Transplantation, focused topic sessions, and a variety of oral and poster presentations. This report is not all-inclusive and focuses on specific research abstracts on key topics in liver transplantation. As always, the new data herein are presented in the context of the published literature to further enhance knowledge in the field. Liver Transpl 19:27–35, 2013. © 2012 AASLD.

Our objective was to determine the safety, efficacy, and pharmacokinetics of telaprevir plus pegylated interferon alfa 2a and ribavirin for chronic, posttransplant genotype 1 hepatitis C virus infection.A prospective, single-arm, multicenter, open-label, phase 2b study was conducted at 22 North American sites to assess the safety, efficacy, and pharmacokinetics of pegylated interferon alfa 2a, ribavirin, and twice daily telaprevir in liver transplant recipients with recurrent, chronic hepatitis C without cirrhosis. Baseline liver biopsies were read by a central pathologist. There were planned safety reviews after a sentinel cohort reached treatment weeks 4 and 16. Serial pharmacokinetic sampling was performed for calcineurin inhibitors, telaprevir, and ribavirin.Sixty-one patients were enrolled and received ≥ 1 dose of study medication; 37 (61%) achieved sustained virologic response. Thirteen of 18 treatment-naive patients (72%), 10 of 11 patients with no or minimal fibrosis (91%), 13 of 15 patients (87%) with interleukin 28B genotype CC, and 36 of 45 patients (80%) with either undetectable or unquantifiable hepatitis C virus RNA at treatment week 4 achieved sustained virologic response. Nine patients (15%) had ≥ 1 drug-related serious adverse event and 7 (11%) discontinued all study drugs due to an adverse event. There were no deaths or acute cellular rejection episodes. During telaprevir treatment, median doses of tacrolimus and cyclosporine were 0.5 mg weekly and 25 mg daily. Target exposures were achieved for telaprevir with twice daily dosing and for ribavirin with reduced initial dosing.Telaprevir combination therapy for posttransplant hepatitis C virus infection yielded superior efficacy than historical controls. Adverse events were similar to, but exceeded, those in immunocompetent patients. Calcineurin inhibitor dosing levels were substantially reduced with telaprevir.

The aim of this study is to assess the impact of obstructive coronary artery disease (CAD) on outcomes after liver transplantation. Patients considered for liver transplantation are at an increased risk for CAD. Obstructive CAD is a contraindication for liver transplantation at most centres. However, the association between severity of CAD and liver transplantation outcomes remains poorly characterized. We retrospectively reviewed 386 consecutive liver transplantations performed between January 2001 and December 2005 at Northwestern Memorial Hospital (NMH). A comparative analysis was conducted for a national cohort (n = 23 820) from the United Network for Organ Sharing database. Outcome measures included patient and graft survival, rates of acute myocardial infarction and heart failure. Patient survival remained similar irrespective of CAD severity or cardiovascular risk index (CRI) in the NMH cohort. The CRI closely correlated with the presence of CAD in the NMH cohort [CRI 0, odds ratio (OR) 0.125, 95% confidence interval (95% CI) 0.02–0.61, P = 0.01; CRI 1, OR 1 reference; CRI ≥2, OR 2.28, 95% CI 1.09–4.75, P = 0.02]. In the national cohort using Cox regression, high (≥2) CRI (reference 0, hazard ratio 1.376, 95% CI 1.271–1.488, P

Although the MELDNa score is now used for liver transplant allocation in the United States, mortality prediction may be underestimated by the score. Using aggregated electronic health record data from 7,834 adult patients with cirrhosis, we determined whether the cause of cirrhosis/cirrhosis complications is associated with an increased risk of death among patients with a MELDNa ≤15 and whether patients with the greatest risk of death could benefit from liver transplantation (LT). Over a median follow-up of 2.3 years, 3,715 patients had a maximum MELDNa score ≤15. 3.4% were wait-listed for LT. Severe hypoalbuminemia, hepatorenal syndrome and hepatic hydrothorax conferred the greatest risk of death independent of MELDNa score with a 1 year predicted mortality >14%. Approximately 10% possessed these risk factors. Of these high risk patients, only 4% were wait-listed for liver transplantation despite no difference in non-liver comorbidities between patients wait-listed and those not listed. Also, risk factors for death among patients wait-listed were the same as those not wait-listed although the effect of malnutrition was significantly greater for wait-listed patients (HR 8.65 CI 2.57-29.11 versus HR 1.47 CI 1.08-1.98). Using the MELDNa score for allocation may continue to limit access to liver transplantation. This article is protected by copyright. All rights reserved.

Acute and chronic alcohol use leads to an impaired immune response and dysregulated inflammatory state that contributes to a markedly increased risk of infection. Via shared mechanisms of immune-mediated injury, alcohol can alter the clinical course of viral infections such as hepatitis B, hepatitis C, and human immunodeficiency virus. These effects are most evident in patients with alcoholic hepatitis and cirrhosis. This article provides an overview of alcohol's effect on the immune system and contribution to the risks and outcomes of specific infectious diseases.

With the increase in patients having impaired renal function at liver transplant due to MELD, accurate predictors of posttransplant native renal recovery are needed to select candidates for simultaneous liver-kidney transplantation (SLK). Current UNOS guidelines rely on specific clinical criteria for SLK allocation. To examine these guidelines and other variables predicting nonrecovery, we analyzed 155 SLK recipients, focusing on a subset (n = 78) that had post-SLK native GFR (nGFR) determined by radionuclide renal scans. The 77 patients not having renal scans received a higher number of extended criteria donor organs and had worse posttransplant survival. Of the 78 renal scan patients, 31 met and 47 did not meet pre-SLK UNOS criteria. The UNOS criteria were more predictive than our institutional criteria for all nGFR recovery thresholds (20-40 mL/min), although at the most conservative cut-off (nGFR ≤ 20) it had low sensitivity (55.3%), specificity (75%), PPV (67.6%) and NPV (63.8%) for predicting post-SLK nonrecovery. On multivariate analysis, the only predictor of native renal nonrecovery (nGFR ≤ 20) was abnormal pre-SLK renal imaging (OR 3.85, CI 1.22-12.5). Our data support the need to refine SLK selection utilizing more definitive biomarkers and predictors of native renal recovery than current clinical criteria.

Magnetic resonance elastography (MRE) can noninvasively measure the stiffness of liver tissue and display this information in anatomic maps. Magnetic resonance imaging (MRI) guidance has not previously been used to biopsy segments of heterogeneous stiffness identified on MRE. Dedicated study of MRE in post-liver transplant patients is also limited. In this study, the ability of real-time MRI to guide biopsies of segments of the liver with different MRE stiffness values in the same post-transplant patient was assessed.MRE was performed in 9 consecutive posttransplant patients with history of hepatitis C. Segments of highest and lower stiffness on MRE served as targets for subsequent real-time MRI-guided biopsy using T2-weighted imaging. The ability of MRI-guided biopsy to successfully obtain tissue specimens was assessed. The Wilcoxon signed-rank test was used to compare mean stiffness differences for highest and lower MRE stiffness segments, with α = 0.05.MRI guidance allowed successful sampling of liver tissue for all (18/18) biopsies. There was a statistically significant difference in mean MRE stiffness values between highest (4.61 ± 1.99 kPa) and lower stiffness (3.03 ± 1.75 kPa) (P = .0039) segments biopsied in the 9 posttransplant patients.Real-time MRI can guide biopsy in patients after liver transplantation based on MRE stiffness values. This study supports the use of MRI guidance to sample tissue based on functional information.

We studied the effects of alemtuzumab on T-regulatory cells (Tregs) during alloactivation, first by differences in depletion of various naive versus alloactivated cell subsets in peripheral blood of healthy volunteers, then by adding serial concentrations to human leukocyte antigen (HLA)-DR-matched and -mismatched responding and stimulating cells in mixed lymphocyte reaction (MLR). Lymphoproliferation inhibition and the development of proliferating carboxyfluorescein succinimidyl ester (CFSE)-diluted CD4(+)CD25(high)CD127(-)FOXP3(+) (phenotypic) Tregs by flow cytometry were measured. Also, the ability of alemtuzumab-treated versus nontreated MLR generated CD4(+)CD127(-) cells to allospecifically inhibit MLRs and recruit additional responding Tregs was tested. We found a more pronounced refractoriness of alloactivated versus naive CD4(+)CD25(high) cells to alemtuzumab induced lymphodepletion. Alemtuzumab dose dependently inhibited lymphoproliferation while amplifying percentages of MLR-generated Tregs. This was somewhat augmented by human complement addition. CD127(-)CD4(+) cells immunoselected after 7 days from alemtuzumab-treated MLRs allospecifically inhibited lymphoproliferation and recruited additional Tregs in fresh MLR-responding cells, similar to modulators derived from MLRs without drug addition (media). Addition of tacrolimus and sirolimus to alemtuzumab further inhibited MLR proliferation. However, Treg percentages were markedly higher with sirolimus. These results support the notion that alemtuzumab induces immunoregulation in naïve T cells undergoing alloactivation absent presensitization, especially used in conjunction with maintenance SRL.

Although pulmonary function tests (PFTs) are routinely performed in patients during the evaluation period before liver transplantation (LT), their utility in predicting post-LT mortality and morbidity outcomes is not known. The aim of this study was to determine the impact of obstructive and/or restrictive lung disease on post-LT outcomes. We conducted a retrospective analysis of patients who had pre-LT PFTs and underwent a subsequent LT (2007-2013). We used statistical analyses to determine independent associations between PFT parameters and outcomes (graft/patient survival, time on ventilator, and hospital/intensive care unit [ICU] length of stay [LOS]). A total of 415 LT recipients with available PFT data were included: 65% of patients had normal PFTs; 8% had obstructive lung disease; and 27% had restrictive lung disease. There was no difference in patient and graft survival between patients with normal, obstructive, and restrictive lung disease. However, restrictive lung disease was associated with longer post-LT time on ventilator and both ICU and hospital LOS (P < 0.05). More specific PFT parameters (diffusing capacity of the lungs for carbon monoxide, total lung capacity, and residual volume) were all significant predictors of ventilator time and both ICU and hospital LOS (P < 0.05). Although pre-LT PFT parameters may not predict post-LT mortality, restrictive abnormalities correlate with prolonged post-LT ventilation and LOS. Efforts to identify and minimize the impact of restrictive abnormalities on PFTs might improve such outcomes. Liver Transplantation 22 805-811 2016 AASLD.

Key Points 1. Current immunological monitoring relies heavily on clinical judgment and therapeutic drug levels and does not adequately assess the functional or donor-specific immunosuppression (IS) status of recipients of liver transplantation (LT). 2. Trough levels of drugs are arbitrary and are more clinically relevant for preventing supratherapeutic or subtherapeutic dosing and blood concentrations and for more closely monitoring at-risk populations (children, the elderly, and patients with organ dysfunction). The AUC or the post-dose levels may be more precise, but they have not been used extensively by transplant centers. 3. Data on drug/immune monitoring specific to LT are fairly limited; therefore, clinical practice is often borrowed from experiences with nonhepatic transplantation (mainly renal transplantation). 4. The monitoring of drug levels in patients taking generic immunosuppressants is challenging because the formulations may change with each prescription. The monitoring of drug or antibody levels is not yet clinically available for biological therapies (induction, lymphocyte-depleting, and maintenance agents). 5. Polymorphisms in drug metabolism (cytochrome P450 and P-glycoprotein) may be useful in selecting the initial and maintenance dosages of immunosuppressants and in preventing complications from over or underimmunosuppression. 6. Future immune monitoring assays should be focused on genomic or immunological predispositions and on specific reactivities to donor antigens to guide the appropriate dosing and minimization of IS after LT. Liver Transpl, 2011. © 2011 AASLD.

Kriss M, Sotil EU, Abecassis M, Welti M, Levitsky J. Mycophenolate mofetil monotherapy in liver transplant recipients. Clin Transplant 2011: 25: E639–E646. © 2011 John Wiley & Sons A/S. Abstract: Introduction: Complete conversion of calcineurin inhibitor (CNI) immunosuppressant therapy to non-nephrotoxic agents such as mycophenolate mofetil (MMF) is controversial, but may be safe in selected patients, although appropriate protocols and long-term benefits of conversion are not well reported. Methods: We analyzed all liver transplant (LT) recipients at our institution who were converted from CNI-based therapy to MMF monotherapy because of renal dysfunction (n = 23) and compared them with patients remaining on CNI-based therapy (n = 23). Renal function, rejection episodes, and markers of CNI-related comorbidities (lipid profile, blood pressure, and glycosylated hemoglobin) were noted. Results: Overall, serum creatinine (SCr) and calculated glomerular filtration rate improved on MMF monotherapy. This improvement was significant when compared with patients who remained on CNI-based therapy. Improvement was most pronounced in patients with milder renal dysfunction (SCr

BACKGROUND Imaging techniques evaluating liver stiffness (magnetic resonance elastography [MRE]) and biomarkers may be useful indicators of fibrosis stage in hepatitis C virus (HCV)+patients. Our aim was to compare the accuracy of MRE and biomarkers in staging fibrosis because of recurrent HCV in liver transplant (LT) recipients with hepatocellular carcinoma. METHODS Liver magnetic resonance imaging and MRE, FIBROSpectII, aspartate aminotransferase-to-platelet ratio index (aspartate aminotransferase [AST]: platelet index), AST:alanine aminotransferase ratio, and magnetic resonance imaging/MRE-guided biopsies targeting the stiffest regions (right and left lobes) were performed in HCV+LT recipients. Sensitivity, specificity, positive predictive value (PPV)/negative predictive value (NPV), and likelihood ratios were calculated for the best cutoff by receiver operating characteristic analysis. RESULTS Thirty-two recipients were included: 28 men, age 60 (±6.4) years, and time since LT 3.25 (±1.68) years. Both MRE (P=0.0001) and FIBROSpectII (P=0.009) were significantly different between no fibrosis and more than or equal to stage 1 groups, whereas aspartate aminotransferase-to-platelet ratio index and AST:alanine aminotransferase ratio were not different. Areas under the receiver operating characteristic curve were 0.87 for MRE and 0.84 for FIBROSpectII. MRE cutoff of 3.81 kPa had 87.5% sensitivity, 79.2% specificity, 58.3% PPV, and 95.0% NPV; FIBROSpectII cutoff of 42 had 87.5% sensitivity, 70.0% specificity, 53.8% PPV, and 93.3% NPV for detection of more than or equal to stage 1 fibrosis. Two patients had high MRE values because of unexpected acute rejection and portal vein thrombosis. CONCLUSIONS MRE and FIBROSpectII are highly sensitive in detecting fibrosis due to recurrent HCV. Both are limited by the low specificity/PPV and confounding because of other graft complications. Values below the MRE and FIBROSpectII cutoffs, however, strongly suggest the absence of fibrosis and may avert the need for protocol biopsy staging.

Every liver transplant (LT) center has had patients who either self-discontinue immunosuppressive (IS) therapy or are deliberately withdrawn due to a research protocol or clinical concern (ie, lymphoproliferative disorder [LPD], overwhelming infection). This is understandable because maintenance IS therapy, particularly calcineurin inhibitors (CNI), is associated with significant cost, side effects, and considerable long-term morbidity and mortality. Detrimental effects of IS therapy include increased risk of cardiovascular disease, metabolic syndrome, bone loss, opportunistic and community-acquired infections, and malignancy. In fact, LT recipients have among the highest rates of chronic kidney disease and associated mortality among all nonkidney solid organ recipients. This mortality is only ameliorated by undergoing a curative kidney transplant, usurping costs and valuable organ resources. The search for improved treatment algorithms includes trial and error CNI dose minimization, the use of alternative IS agents (antimetabolites, mammalian target of rapamycin [mTOR] inhibitors), or even complete CNI withdrawal. Yet those who are successful in achieving such operational tolerance (no immunosuppression and normal allograft function) are considered lucky. The vast majority of recipients will fail this approach, develop acute rejection or immune-mediated hepatitis, and require resumption of IS therapy. As such, withdrawal of IS following LT is not standard-of-care, leaving clinicians to currently maintain transplant patients on IS therapy for life. Nonetheless, the long-term complications of all IS therapies highlight the need for strategies to promote immunologic or operational tolerance. Clinically applicable biomarker assays signifying the potential for tolerance as well as tolerogenic IS conditioning are invariably needed if systematic, controlled rather than "hit or miss" approaches to withdrawal are considered. This review will provide an overview of the basic mechanisms of tolerance, particularly in relation to LT, data from previous IS withdrawal protocols and biomarker studies in tolerant recipients, and a discussion on the prospect of increasing the clinical feasibility and success of withdrawal.

OBJECTIVE. The purpose of our study was to compare the utility of MR elastography (MRE) and diffusion-weighted imaging (DWI) in characterizing fibrosis and chronic hepatitis in patients with chronic liver diseases.SUBJECTS AND METHODS. Seventy-six patients with chronic liver disease underwent abdominal MRI, MRE, and DWI. Severities of liver fibrosis and chronic hepatitis were graded by histopathologic analysis according to standard disease-specific classifications. The overall predictive ability of MRE and DWI in assessment of fibrosis was compared by constructing a receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC) on the basis of histopathologic analysis.RESULTS. Using ROC analysis, MRE showed greater capability than DWI in discriminating stage 2 or greater (≥ F2), stage 3 or greater (≥ F3), and cirrhosis (≥ F4), shown as significant differences in AUC (p = 0.003, p = 0.001, and p = 0.001, respectively). Higher sensitivity and specificity were shown by MRE in pr...

Limited data exist for the use of alemtuzumab (AL) induction in liver transplantation (LT) recipients. We compared the outcomes of hepatitis C virus-negative LT recipients who received AL induction followed by tacrolimus and mycophenolate mofetil without steroids to cohort who received no AL induction, tacrolimus, and a steroid taper. Fifty-five AL-induced recipients were compared to 85 non-AL-induced recipients with similar characteristics. Two-year patient survival (80% versus 88.2%, P = 0.0665) and graft survival (76.4% versus 82.4%, P = 0.1792) were not significantly different between the AL and non-AL groups, respectively. Other outcomes, including acute rejection (20% versus 30.3%), renal dysfunction (creatinine levels: 1.3 ± 0.3 versus 1.4 ± 0.6 mg/dL), and immunosuppressant monotherapy (29.1% versus 44.3%), were not significantly different between the AL and non-AL groups, respectively (P > 0.05). The number of rejection episodes (12 versus 42, P = 0.02) and the number of patients with new-onset hypertension (3 versus 15, P = 0.03) were lower in the AL group, although the incidence of all posttransplant infections was higher with AL (63.6% versus 44.3%, P = 0.03), primarily because of an increase in viral infections. In conclusion, a steroid-free AL induction regimen was associated with less hypertension and rejection but with more infectious complications; thus, the overall benefit of AL induction in LT recipients is called into question.