Acceptable outcomes of liver transplantation in uninsured patients under the coverage of a state assistance program.

The lack of health insurance is a major barrier in the access to healthcare even in case of life-saving procedures such as liver transplantation (LT). Concerns about worse outcomes in uninsured patients have also discouraged the evaluation and transplantation of patients without adequate health insurance coverage. The aim of this study is to evaluate outcomes from the largest cohort of uninsured patients who underwent LT with the support of a state payment assistance program (also called charity care). This study included all consecutive patients who underwent LT at a single center from 2002 to 2020. Demographic, clinical, social variables and outcome metrics were collected and compared between insured and uninsured patients. Among a total of 978 LT recipients, 594 had private insurance, 324 government insurance (Medicare/Medicaid), 60 were uninsured and covered under a state charity care program. In the charity care group, there was a higher proportion of Hispanic subjects, single marital status, younger age, and high-MELD score patients. The 1- and 3-year patient survival rates were 89.0% and 81.8% in private insurance patients, 88.8% and 80.1% in government insurance recipients, and 93.3% and 79.6% in those with charity care (p=0.49). There was no difference in graft survival between insured and uninsured patients (p=0.62). The three insurance groups presented similar hospital length-of-stay and 30-day readmission rates. In both univariate and multivariate analysis, uninsured status (charity care) was not associated with worse patient survival (HR:1.23, 95%CI: 0.84-1.80, p=0.29) or graft survival (HR:1.22, 95%CI:0.84-1.78, p=0.29). In conclusion, there was no difference in outcomes after LT between insured and uninsured patients. A charity care program may be an effective tool to mitigate socio-economic disparities in both outcomes and access to LT.

Liver biopsy in assessment of extended criteria donors.

The safety and liver utilization with prerecovery liver biopsy (PLB) in extended criteria liver donors are unclear. We conducted a retrospective cohort study in 1323 brain death donors (PLB = 496) from 3 organ procurement organizations (OPOs). Outcomes were complications, preempted liver recovery (PLR), and liver transplantation (LT). Additional analyses included liver-only and propensity score-matched multiorgan donor subgroups. PLB donors were older (57 versus 53 years; P < 0.001). Hepatitis C antibody positivity (14.3% versus 9.6%, P = 0.01) and liver-only donors (42.6% versus 17.5%; P < 0.001) were more prevalent. The PLB cohort had fewer complications (31.9% versus 42.3%; P < 0.001). In the PLB cohort, PLR was significantly higher (odds ratio [OR], 3.45; 95% confidence interval [CI], 2.42-4.92) and LT lower (OR, 0.69; 95% CI, 0.52-0.91). In liver-only and propensity score-matched multiorgan donor subgroups, PLR was significantly higher (OR, 1.76; 95% CI, 1.06-2.94 and OR, 2.29; 95% CI, 1.37-3.82, respectively) without a decrease in LT (OR, 0.71; 95% CI, 0.43-1.18 and OR, 0.91; 95% CI, 0.63-1.33, respectively) in PLB subgroups. In conclusion, in extended criteria liver donors, PLB is safe and decreases futile liver recovery without decreasing LT. Increased use of PLB, especially in liver-only donors, is likely to save costs to OPOs and transplant centers and improve efficiencies in organ allocation. Liver Transplantation 24 182-191 2018 AASLD.

A multicenter study of 30 days complications after deceased donor liver transplantation in the model for end-stage liver disease score era.

Knowledge of risk factors for posttransplant complications is likely to improve patient outcomes. Few large studies of all early postoperative complications after deceased donor liver transplantation (DDLT) exist. Therefore, we conducted a retrospective, cohort study of 30-day complications, their risk factors, and the impact on outcomes after DDLT. Three centers contributed data for 450 DDLTs performed from January 2005 through December 2009. Data included donor, recipient, transplant, and outcome variables. All 30-day postoperative complications were graded by the Clavien-Dindo system. Complications per patient and severe (≥ grade III) complications were primary outcomes. Death within 30 days, complication occurrence, length of stay (LOS), and graft and patient survival were secondary outcomes. Multivariate associations of risk factors with complications and complications with LOS, graft survival, and patient survival were examined. Mean number of complications/patient was 3.3 ± 3.9. At least 1 complication occurred in 79.3%, and severe complications occurred in 62.8% of recipients. Mean LOS was 16.2 ± 22.9 days. Graft and patient survival rates were 84% and 86%, respectively, at 1 year and 74% and 76%, respectively, at 3 years. Hospitalization, critical care, ventilatory support, and renal replacement therapy before transplant and transfusions during transplant were the significant predictors of complications (not the Model for End-Stage Liver Disease score). Both number and severity of complications had a significant impact on LOS and graft and patient survival. Structured reporting of risk-adjusted complications rates after DDLT is likely to improve patient care and transplant center benchmarking. Despite the accomplished reductions in transfusions during DDLT, opportunities exist for further reductions. With increasing transplantation of sicker patients, reduction in complications would require multidisciplinary efforts and institutional commitment. Pretransplant risk characteristics for complications must factor in during payer contracting.

Prerecovery liver biopsy in the brain-dead donor: a case-control study of logistics, safety, precision, and utility.

Prerecovery liver biopsy (PLB) can potentially to decrease futile recovery and increase utilization of marginal brain-dead donor (BDD) livers. A case-control study was conducted to examine the logistics, safety, histological precision, and liver utilization associated with PLB in BDDs. Twenty-three cases between January 2008 and January 2013 were compared to 2 groups: 48 sequential and 69 clinically matched controls. Compared to the sequential controls, the cases were older (53 versus 46 years), heavier (30.2 versus 25.8 kg/m2), had higher prevalences of hypertension (78.3% versus 44.7%) and alcohol use (56.5% versus 23.4%), and a lower United Network for Organ Sharing expected organ yield (0.73 versus 0.81 livers/donor; P < 0.05 for all). Baseline characteristics were similar between cases and clinical controls. Donor management time was longer for the cases (22.4 hours) versus sequential controls (16.5 hours, P = 0.01) and clinical controls (15.9 hours, P = 0.01). Complications for cases (8.7%) were not different from either group of controls (18.8% for sequential controls, P = 0.46; 17.4% for clinical controls, P = 0.50). The agreement between the donor hospital and study pathologists was substantial regarding evaluation of steatosis (κ = 0.623) and fibrosis (κ = 0.627) and moderate regarding inflammation (κ = 0.495). The proportions of livers that were transplanted were similar for the cases and the clinical controls (60.9% versus 59.4%). In contrast, the proportion of donors for whom liver recovery was not attempted was higher (30.4% versus 8.7%), and the proportion of attempted liver recoveries that did not result in transplantation was lower (8.7% versus 31.9%). These differences were significant at P = 0.009. Overall, PLB is logistically feasible with only a minimal delay and is safe, its interpretation at donor hospitals is reproducible, and it appears to decrease futile liver recovery.

Calcineurin inhibitor-free mycophenolate mofetil/sirolimus maintenance in liver transplantation: the randomized spare-the-nephron trial.

Mycophenolate mofetil (MMF) and sirolimus (SRL) have been used for calcineurin inhibitor (CNI) minimization to reduce nephrotoxicity following liver transplantation. In this prospective, open-label, multicenter study, patients undergoing transplantation from July 2005 to June 2007 who were maintained on MMF/CNI were randomized 4 to 12 weeks after transplantation to receive MMF/SRL (n = 148) or continue MMF/CNI (n = 145) and included in the intent-to-treat population. The primary efficacy endpoints were the mean percentage change in the calculated glomerular filtration rate (GFR) and a composite of biopsy-proven acute rejection (BPAR), graft lost, death, and lost to follow-up 12 months after transplantation. Patients were followed for a median of 519 days after randomization. MMF/SRL was associated with a significantly greater renal function improvement from baseline with a mean percentage change in GFR of 19.7 ± 40.6 (versus 1.2 ± 39.9 for MMF/CNI, P = 0.0012). The composite endpoint demonstrated the noninferiority of MMF/SRL versus MMF/CNI (16.4% versus 15.4%, 90% confidence interval = -7.1% to 9.0%). The incidence of BPAR was significantly greater with MMF/SRL (12.2%) versus MMF/CNI (4.1%, P = 0.02). Graft loss (including death) occurred in 3.4% of the MMF/SRL-treated patients and in 8.3% of the MMF/CNI-treated patients (P = 0.04). Malignancy-related deaths were less frequent with MMF/SRL. Adverse events caused withdrawal for 34.2% of the MMF/SRL-treated patients and for 24.1% of the MMF/CNI-treated patients (P = 0.06). The use of MMF/SRL is an option for liver transplant recipients who can benefit from improved renal function but is associated with an increased risk of rejection (but not graft loss).

New index for assessing the chronotropic response in patients with end-stage liver disease who are undergoing dobutamine stress echocardiography.

The inability to achieve 85% of the maximum predicted heart rate (MPHR) on dobutamine stress echocardiography (DSE) is defined as chronotropic incompetence and is a predictor of major cardiac events after orthotopic liver transplantation (OLT). The majority of patients with end-stage liver disease (ESLD) receive beta-blockers for the prevention of variceal bleeding. In these patients, it is impossible to determine whether chronotropic incompetence is secondary to cirrhosis-related autonomic dysfunction or is merely a beta-blocker effect. We evaluated the usefulness of the maximum achieved heart rate (MAHR) and the heart rate reserve (HRR) in the detection of chronotropic incompetence in ESLD patients on beta-blocker therapy before DSE. We also evaluated the usefulness of a new index, the modified heart rate reserve (MHRR), in diagnosing chronotropic incompetence and predicting major cardiovascular adverse events after OLT. The study population consisted of 284 ESLD patients. The mean values of MAHR (expressed as a percentage of 85% of MPHR) and HRR were significantly lower for patients on beta-blockers versus patients off beta-blockers [97.1% versus 101.6% (t = 5.01, P < 0.001) and 71.7% versus 77.3% (t = 4.03, P < 0.001), respectively], whereas the values of MHRR were similar in patients on beta-blockers and patients off beta-blockers [102.3% versus 102.1% (t = 0.04, P = 0.97)]. A regression analysis showed a significant association of MAHR (P < 0.001) and HRR (P < 0.001) with beta-blockers, whereas MHRR was not associated with beta-blocker treatment (P = 0.92). MAHR and HRR were found to have no value for diagnosing chronotropic incompetence in ESLD patients. MHRR was not affected by beta-blocker therapy. Patients who developed heart failure (HF) and myocardial infarction (MI) after OLT had significantly lower MHRR values according to pretransplant DSE. MHRR was significantly associated with the subsequent development of HF (P = 0.01) and MI (P = 0.01) after OLT. MHRR may be useful for the determination of the target heart rate for stress testing, the diagnosis of chronotropic incompetence, and the prediction of adverse cardiac events after OLT.

Self-reported non-adherence to immune-suppressant therapy in liver transplant recipients: demographic, interpersonal, and intrapersonal factors.

Adherence to immune suppressants and follow-up care regimen is important in achieving optimal long-term outcomes after organ transplantation. To identify patients most at risk for non-adherence, this cross-sectional, descriptive study explores the prevalence and correlates of non-adherence to immune-suppressant therapy among liver recipients. Anonymous questionnaires mailed consisted of the domains: (i) adherence barriers to immune suppressants, (ii) immune suppressants knowledge, (iii) demographics, (iv) social support, (v) medical co-morbidities, and (vi) healthcare locus of control and other beliefs. Overall response was 49% (281/572). Data analyzed for those transplanted within 10 yr of study reveal 50% (119/237) recipients or 9.2/100 person years reporting non-adherence. Non-adherence was reported highest in the 2-5 yr post-transplant phase (69/123, 56%). The highest immune-suppressant non-adherence rates were in recipients who are: divorced (26/34, 76%, p=0.0093), have a history of substance or alcohol use (42/69, 61%, p=0.0354), have mental health needs (50/84, 60%, p=0.0336), those who missed clinic appointments (25/30, 83%, p<0.0001), and did not maintain medication logs (71/122, 58%, p=0.0168). Respondents who were non-adherent with physician appointments were more than four and a half times as likely (OR 4.7, 95% CI 1.5-14.7, p=0.008) to be non-adherent with immune suppressants. In conclusion, half of our respondents report non-adherence to immune suppressants. Factors identified may assist clinicians to gauge patients' non-adherence risk and target resources.

A randomized, multicenter study comparing steroid-free immunosuppression and standard immunosuppression for liver transplant recipients with chronic hepatitis C.

This randomized, prospective, multicenter trial compared the safety and efficacy of steroid-free immunosuppression (IS) to the safety and efficacy of 2 standard IS regimens in patients undergoing transplantation for hepatitis C virus (HCV) infection. The outcome measures were acute cellular rejection (ACR), severe HCV recurrence, and survival. The patients were randomized (1:1:2) to tacrolimus (TAC) and corticosteroids (arm 1; n = 77), mycophenolate mofetil (MMF), TAC, and corticosteroids (arm 2; n = 72), or MMF, TAC, and daclizumab induction with no corticosteroids (arm 3; n = 146). In all, 295 HCV RNA-positive subjects were enrolled. At 2 years, there were no differences in ACR, HCV recurrence (biochemical evidence), patient survival, or graft survival rates. The side effects of IS did not differ, although there was a trend toward less diabetes in the steroid-free group. Liver biopsy samples revealed no significant differences in the proportions of patients in arms 1, 2, and 3 with advanced HCV recurrence (ie, an inflammation grade ≥ 3 and/or a fibrosis stage ≥ 2) in years 1 (48.2%, 50.4%, and 43.0%, respectively) and 2 (69.5%, 75.9%, and 68.1%, respectively). Although we have found that steroid-free IS is safe and effective for liver transplant recipients with chronic HCV, steroid sparing has no clear advantage in comparison with traditional IS.

The Impact of Chronic Liver Disease on Postoperative Outcomes and Resource Utilization.

BACKGROUND: Multiple studies have shown high rates of postoperative morbidity and mortality in individuals with chronic liver disease (CLD). However, analyses from comparisons with individuals without CLD are not available. Such analyses might provide opportunities to improve outcomes. METHODS: Data from The National Surgical Quality Improvement Program (NSQIP) from 2008 to 2011 were analyzed comparing CLD patients undergoing non-liver surgery propensity matched to those without CLD. Patients with CLD were stratified by Model of End Stage Liver Disease (MELD) scores <15 and ≥15. Primary outcome was all cause mortality, and secondary outcomes were composite and individual morbidity, hospital length of stay, readmission, reoperation, and discharge destination. Odds ratios (OR) were calculated, and length of hospital stay was estimated using Poisson regression. RESULTS: There were 6,209 patients with CLD (4,013 with low MELD, 2,196 with high MELD) matched to 18,627 patients without. Patients with CLD had 1.8- and 3.3-times higher odds of mortality (95% CI 1.6-2.1 for Low MELD (10.6%), 2.9-3.8 for high MELD (35.2%), and 1.8- and 2.2-times higher odds of any morbidity (1.6-1.9 and 1.9-2.4). Complications specific to CLD were increased based on MELD specifically coma (OR 1.6, 0.9-2.9 for Low MELD, 2.2, 1.5-3.2 for High MELD), renal failure (OR 1.4, 1.1-1.8 and 2.4, 2.0-2.9), and bleeding (OR 1.7, 1.5-1.9 and 2.0, 1.8-2.3). They also had a 20% and 80% longer length of stay, 2.2- and 3.4-times higher odds of being discharged somewhere other than home, 1.7- and 1.6-times higher odds of readmission, and 1.5- and 1.6-times higher odds of reoperation. CONCLUSION: Patients with CLD have significantly higher odds of mortality and morbidity, which is increased with a higher MELD. Interventions that decrease those morbidities are needed and have the potential to decrease mortality and resource utilization.

Global gene expression profiles of ischemic preconditioning in deceased donor liver transplantation.

The benefits of ischemic preconditioning (IPC) in reducing ischemia/reperfusion injury (IRI) remain indistinct in human liver transplantation (LT). To further understand mechanistic aspects of IPC, we performed microarray analyses as a nested substudy in a randomized trial of 10-minute IPC in 101 deceased donor LTs. Liver biopsies were performed after cold storage and at 90 minutes postreperfusion in 40 of 101 subjects. Global gene expression profiles in 6 biopsy pairs in IPC and work standard organ recovery groups at both time points were compared using the Affymetrix GeneChip Human Gene 1.0 ST array. Transcripts with >1.5-fold change and P < 0.05 were considered significant. IPC altered expression of 82 transcripts in antioxidant, immunological, lipid biosynthesis, cell development and growth, and other groups. Real-time polymerase chain reaction and immunoblotting validated our microarray data. IPC-induced overexpression of glutathione S-transferase mu transcripts (GSTM1, GSTM3, GSTM4, and GSTM5) was accompanied by increased protein expression and may contribute to a decrease in oxidative stress. However, the increased expression of fatty acid synthase may increase oxidative stress, and tumor necrosis factor ligand superfamily member 10 may promote apoptosis. These changes, in combination with decreased expression of heparin-binding epidermal growth factor-like growth factor and insulin-like growth factor binding protein-1, both of which inhibit apoptosis, may increase IRI. In our study of deceased donor LT, IPC induces changes in gene expression, some of which are potentially beneficial but some which are potentially injurious. Thus, our findings of changes in gene expression mirror the outcomes in our clinical trial.

Ischemic preconditioning of the liver: a few perspectives from the bench to bedside translation.

Utilization of ischemic preconditioning to ameliorate ischemia/reperfusion injury has been extensively studied in various organs and species for the past two decades. While hepatic ischemic preconditioning in animals has been largely beneficial, translational efforts in the two clinical contexts--liver resection and decreased donor liver transplantation--have yielded mixed results. This review is intended to critically examine the translational data and identify some potential reasons for the disparate clinical results, and highlight some issues for further studies.

Surgical treatment of hepatocellular carcinoma beyond Milan criteria. Results of liver resection, salvage transplantation, and primary liver transplantation.

BACKGROUND: There is no clear consensus regarding the best treatment strategy for patients with advanced hepatocellular carcinoma (HCC). METHODS: Patients with cirrhosis and HCC beyond Milan who had undergone liver resection (LR) or primary orthotopic liver transplantation (OLT) between November 1995 and December 2005 were included in this study. Pathological tumor staging was based on the American Liver Tumor Study Group modified Tumor-Node-Metastasis classification. RESULTS: A total of 23 HCC patients were primarily treated by means of LR, 5 of whom eventually underwent salvage OLT. An additional 32 patients underwent primary OLT. The overall actuarial survival rates at 3 and 5 years were 35% after LR, and 69% and 60%, respectively, after primary OLT. Recurrence-free survival at 5 years was significantly higher after OLT (65%) than after LR (26%). Of the patients who underwent LR, 11 (48%) experienced HCC recurrence only in the liver; 6 of these 11 presented with advanced HCC recurrence, poor medical status, or short disease-free intervals and were not considered for transplantation. Salvage OLT was performed in 5 patients with early stage recurrence (45% of patients with hepatic recurrence after LR and 22% of all patients who underwent LR). At a median of 18 months after salvage OLT, all 5 patients are alive, 4 are free of disease, and 1 developed HCC recurrence 16 months after salvage OLT. CONCLUSION: For patients with HCC beyond Milan criteria, multimodality treatment-including LR, salvage OLT, and primary OLT-results in long-term survival in half of the patients. When indicated, LR can optimize the use of scarce donor organs by leaving OLT as a reserve option for early stage HCC recurrence.

Preoperative fine needle aspiration cytology diagnosis of microcystic adenoma of the pancreas: fact or fiction? A report of 2 cases.

BACKGROUND: Microcystic adenoma is an uncommon benign neoplasm involving the pancreas that usually affects older populations. These neoplasms often enlarge to significant sizes, causing symptoms of obstruction and discomfort. CASES: We report 2 cases of microcystic adenoma of the pancreas in which an accurate diagnosis could not be rendered on cytology material alone. Bench fine needle aspiration (FNA) biopsy performed on the resection specimen in one of the cases had a higher cellular yield because a different technique was used to prepare the slide. CONCLUSION: A preoperative diagnosis can be helpful in guiding the care of the patient, thereby increasing the importance of a diagnosis to distinguish between a benign vs. malignant process. These case reports demonstrate the difficulty of obtaining diagnostic cells in microcystic adenoma, highlight the use of FNA to increase cellular yield and emphasize the importance of correlating radiologic findings with aspiration of abundant watery fluid from cystic pancreatic masses to make a definitive diagnosis.

Improved Outcomes Following Hepatocellular Carcinoma (HCC) Diagnosis in Patients Screened for HCC in a Large Academic Liver Center versus Patients Identified in the Community.

Background and Aims: Hepatocellular carcinoma (HCC) is the sixth most commonly occurring cancer worldwide. Knowledge and adherence to HCC surveillance guidelines has been associated with earlier detection. We sought to evaluate characteristics and outcomes following HCC diagnosis in patients screened for HCC in a large academic liver center versus patients diagnosed and referred from the community. Methods: We reviewed the records of patients diagnosed with HCC in the liver center of an academic institution from January 1999 till December 2013. Patients were classified into two groups: patients followed in our hepatology clinic and patients with HCC recently referred to our center. Univariate analysis was performed using chi-squared test and multivariate analysis was performed using SPSS 22.0. Results: The records of 410 patients were reviewed, and included 77.3% of patients referred from the community and 22.7% of patients followed in our clinic. In the clinic group, 75.6% were identified with one nodule at initial diagnosis, compared to 65.6% in the referral group. Patients in the referral group were more likely to present with tumors ≥5 cm at diagnosis, with 28.7% compared to 5.4% in the clinic group (p < 0.0001). Patients referred from the community were also less likely to undergo transplant, with 32.2% as compared to 48.4% of the clinic group (p < 0.004). Conclusion: Patients with chronic liver disease managed in an academic liver center present in the early stage of HCC diagnosis and are more likely to meet the Milan criteria and undergo transplant. Early referral to a specialized transplant center, if feasible, where a multidisciplinary approach is utilized might be essential in the management of chronic liver disease.

Organ Procurement Organization Survey of Practices and Beliefs Regarding Prerecovery Percutaneous Liver Biopsy in Donation After Neurologic Determination of Death.

BACKGROUND: Prerecovery liver biopsy (PLB) allows histological evaluation of the organ before procurement. The opinions and what factors might influence PLB use within Organ Procurement Organizations (OPOs) are unknown. METHODS: A survey instrument was distributed by the Association of OPOs to the clinical directors of all 58 OPOs. Descriptive statistics were calculated. Results were also stratified based on OPO characteristics. RESULTS: Forty-nine (84.5%) of 58 OPOs responded to the survey; 40 (81.6%) of 49 currently perform PLB. This did not vary based on land mass, population, livers discarded, transplanted, donor age, or recipient MELD scores. Donor age, obesity, alcohol abuse, hepatitis serology, liver only donor, imaging results, and transplant center request were the most common indications for PLB in over 80% of OPOs. The median rate of performance is 5% to 10% of donors. Most use interventional radiologists to perform and the donor hospital pathologist/s to interpret PLB. Most OPOs believe PLBs are safe, reliable, useful, and performed often enough. Most say they did not believe they are easy to obtain. Beliefs were mixed regarding accuracy. The topics likely to influence PLB use were utility and accuracy of PLB, and availability of staff to perform PLB. OPOs that perform PLB more often were more likely to have favorable opinions of safety and pathologist availability, and more influenced by safety, reliability, availability, and a national consensus on the use of PLB. CONCLUSIONS: Considerable variability exists in the use of PLB. Additional information on the utility, accuracy, and safety of PLB are needed to optimize its use.

Effect of Early Everolimus-Facilitated Reduction of Tacrolimus on Efficacy and Renal Function in De Novo Liver Transplant Recipients: 24-Month Results for the North American Subpopulation.

BACKGROUND: A recent randomized phase III study of 719 de novo liver transplant recipients showed that early everolimus plus reduced-dose tacrolimus (EVR + rTAC) led to significantly better kidney function than standard TAC (TAC-C), without compromising efficacy. In that study, patients from North America (n = 211) had increased risk factors for posttransplant renal insufficiency at study start, relative to patients from Europe and rest of world (eg, worse renal function, more diabetes, older age). METHODS: A post hoc analysis was performed to assess whether these regional disparities affected study outcomes in North American patients. RESULTS: In this subpopulation, estimated glomerular filtration rates at randomization were higher in TAC-C over EVR + rTAC (76.4 vs 69.3 mL/min per 1.73 m). Mean changes in estimated glomerular filtration rate values (mL/min per 1.73 m) favored EVR + rTAC over TAC-C at months 12 (+3.7 vs -4.5; P = 0.032), 24 (+2.7 vs -6.6; P = 0.042), and 36 (+4.3 vs -8.1; P = 0.059). The composite efficacy endpoint of treated biopsy-proven acute rejection, graft loss, or death was 10.9%, 14.1%, and 14.1% for EVR + rTAC and 13.1%, 17.2%, and 19.3% for TAC-C at months 12, 24, and 36, respectively. CONCLUSIONS: Although the North American cohort had more comorbidities, results were consistent with the overall population for efficacy and renal function.

Steroid-Mediated Decrease in Blood Mesenchymal Stem Cells in Liver Transplant could Impact Long-Term Recovery.

Orthotopic liver transplant (OLT) remains the standard of care for end stage liver disease. To circumvent allo-rejection, OLT subjects receive gluococorticoids (GC). We investigated the effects of GC on endogenous mesenchymal stem (stromal) cells (MSCs) in OLT. This question is relevant because MSCs have regenerative potential and immune suppressor function. Phenotypic analyses of blood samples from 12 OLT recipients, at pre-anhepatic, anhepatic and post-transplant (2 h, Days 1 and 5) indicated a significant decrease in MSCs after GC injection. The MSCs showed better recovery in the blood from subjects who started with relatively low MSCs as compared to those with high levels at the prehepatic phase. This drop in MSCs appeared to be linked to GC since similar change was not observed in liver resection subjects. In order to understand the effects of GC on decrease MSC migration, in vitro studies were performed in transwell cultures. Untreated MSCs could not migrate towards the GC-exposed liver tissue, despite CXCR4 expression and the production of inflammatory cytokines from the liver cells. GC-treated MSCs were inefficient with respect to migration towards CXCL12, and this correlated with retracted cytoskeleton and motility. These dysfunctions were partly explained by decreases in the CXCL12/receptor axis. GC-associated decrease in MSCs in OLT recipients recovered post-transplant, despite poor migratory ability towards GC-exposed liver. In total, the study indicated that GC usage in transplant needs to be examined to determine if this could be reduced or avoided with adjuvant cell therapy.