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The introduction of safe and highly effective direct acting antivirals (DAAs) has significantly improved hepatitis C virus (HCV) treatment outcomes after transplant. The solid organ transplant community has sought to identify strategies aimed at increasing the donor pool including the utilization of HCV-viremic organs in HCV-negative recipients. We will review the existing literature to evaluate DAA use for the treatment of HCV viremia post-liver transplant in patients who receive HCV-viremic allografts. A PubMed search was conducted and references for each study were also reviewed to identify additional articles. Randomized controlled trials, cohort studies, case series, and case reports were included if: published in English language, evaluated DAA treatment outcomes after liver only or simultaneous liver-kidney transplantation with HCV-viremic allografts in HCV-negative recipients, and had full-text article availability. Our review included 16 studies and 2 case reports. The majority of liver transplant recipients were treated with a pangenotypic DAA for 12 weeks with a heterogeneous median time to initiation (range 1.7-118 days). Sustained virologic response was assessed in 253 liver transplant patients with 99.6% achieving cure with minimal DAA-attributed adverse drug events. There were 23 reported episodes of rejection, 12 deaths, and 1 graft loss among all studies. Treatment with DAA after transplantation of HCV-viremic livers into HCV-negative recipients appears to be safe and effective; however, long-term outcomes remain unknown. Transplant pharmacists play a key role in the development of center-specific protocols to optimize post-transplant outcomes in this unique patient population.

The pharmacokinetic profiles of medications are altered in overweight and underweight patients, but few studies have described these differences in patients with body mass index extremes. As solid organ transplant programs expand their candidate selection criteria to accommodate a growing population of patients with weight extremes, it has become imperative to understand and evaluate the impact weight extremes have on the pharmacokinetics of life-sustaining immunosuppression in this population. This review will describe pharmacokinetic and dosing considerations for weight extremes in solid organ transplant recipients, including changes following bariatric surgeries, non-pharmacologic and pharmacologic management strategies for weight loss and gain, and potential drug-drug interactions with popular weight management products.

Despite adverse effects like hyperglycemia, new-onset diabetes after transplant (NODAT), and infectious complications, corticosteroid use remains an important part of liver transplantation (LT) immune suppression. Budesonide, a synthetic corticosteroid, undergoes extensive first-pass hepatic metabolism with only 10% systemic bioavailability, providing an opportunity for an improved toxicity-therapeutic ratio. Although effective in the treatment of autoimmune hepatitis, the effects of budesonide for LT immune suppression are unknown. We conducted a single-center phase 2a trial to study the safety and efficacy of budesonide immunosuppressive therapy. From July 2017 to November 2018, 20 patients undergoing a first LT received budesonide tapering doses (from 9 to 3 mg) for 12 weeks. Patients were compared with matched control patients who received prednisone from the same time period. Additionally, both groups received calcineurin inhibitors and mycophenolate mofetil. Outcome measures at week 24 included rates of biopsy-proven acute cellular rejection (ACR), NODAT (hemoglobin A1c >6.4%), and infectious complications. In the budesonide arm, 1 patient developed ACR at week 5 and was removed from the study. Another patient stopped the study drug at week 8 due to persistent nausea. Rates of ACR were similar between the budesonide and control groups (5% versus 5%, P = 1.00). Three patients in the control group developed NODAT versus none in the budesonide group (15% versus 0%; P = 0.23). There were 6 infections in the control group compared with none in the budesonide group (30% versus 0; P = 0.02). These pilot data suggest that budesonide has the potential to be a safe and effective alternative to prednisone for LT immune suppression while reducing steroid-induced infections and NODAT. Randomized controlled trials are required to validate these findings.

Because of underutilization of liver allografts, our center previously showed that hepatitis C virus (HCV) antibody-positive/nucleic acid test (NAT)-negative livers when transplanted into HCV nonviremic recipients were safe with a 10% risk of HCV transmission. Herein, we present our single-center prospective experience of using HCV NAT+ liver allografts transplanted into HCV NAT- recipients. An institutional review board-approved matched cohort study was conducted examining post- liver transplantation (LT) outcomes of HCV- patients who received HCV NAT+ organs (treatment group) compared with matched recipients with HCV NAT- organs (matched comparator group) between June 2018 to October 2019. The primary endpoint was success of HCV treatment and elimination of HCV infection. The secondary outcomes included the 30-day and 1-year graft and patient survival as well as perioperative complications. There were 32 recipients enrolled into each group. Because of 1 death in the index admission, 30/31 patients (97%) were given HCV treatment at a median starting time of 47 days (18-140 days) after LT. A total of 19 (63%) patients achieved sustained virological response at week 12 (SVR12). Another 6 patients achieved end-of-treatment response, while 5 remained on therapy and 1 is yet to start treatment. No HCV treatment failure has been noted. There were no differences in 30-day and 1-year graft and patient survival, length of hospital stay, biliary or vascular complications, or cytomegalovirus viremia between the 2 groups. In this interim analysis of a matched cohort study, which is the first and largest study to date, the patients who received the HCV NAT+ organs had similar outcomes regarding graft function, patient survival, and post-LT complications.

Objectives The aim of this study was to assess the 1-year safety and effectiveness of HBV Nucleic Acid Test positive (HBV NAT+) allografts in seronegative kidney transplant (KT) and liver transplant (LT) recipients. Summary background data Despite an ongoing organ shortage, the utilization of HBV NAT+ allografts into seronegative recipients has not been investigated. Methods From January 2017 to October 2020, a prospective cohort study was conducted among consecutive KT and LT recipients at a single institution. Primary endpoints were post-transplant HBV viremia, graft and patient survival. Results With median follow-up of 1-year, there were no HBV-related complications in the 89 HBV NAT+ recipients. Only 9 of 56 KTs (16.1%) and 9 of 33 LTs (27.3%) experienced post-transplant HBV viremia at a median of 185 (KT) and 269 (LT) days postoperatively. Overall, viremic episodes resolved to undetected HBV DNA after a median of 80 days of entecavir therapy in 16 of 18 recipients. Presently, 100% of KT recipients and 93.9% of LT recipients are HBV NAT- with median follow-up of 13 months, whereas 0 KT and 8 LT (24.2%) recipients are HBV surface antigen positive indicating chronic infection. KT and LT patient and allograft survival were not different between HBV NAT+ and HBV NAT- recipients (P > 0.05), whereas HBV NAT+ KT recipients had decreased waitlist time and pretransplant duration on dialysis (P Conclusions This is the largest series describing the transplantation of HBV NAT+ kidney and liver allografts into HBV seronegative recipients without chronic HBV viremia or decreased 1-year patient and graft survival. Increasing the utilization of HBV NAT+ organs in nonviremic recipients can play a role in decreasing the national organ shortage.

This study assesses the impact of a telemedicine-based home management program (THMP) on patient adherence, hospital readmissions, and quality of life (QOL) after liver transplantation (LT).Telemedicine interventions represent an opportunity to personalize care and can lead to improved adherence and patient satisfaction. However, there is limited data on impact of these interventions on outcomes after LT. Therefore, we conducted the first randomized controlled trial (RCT) of a THMP compared to standard of care (SOC) after LT.One hundred six consecutive LT recipients were randomized (1:1) to 1 of 2 posttransplant care strategies: SOC or THMP. The THMP included an electronic tablet and bluetooth devices to support daily text messages, education videos, and video FaceTime capability; data was cyber-delivered into our electronic medical record daily. Endpoints were THMP participation, 90-day hospital readmission rate, and QOL.One hundred patients completed the study with 50 enrolled in each arm. Participation and adherence with telemedicine was 86% for basic health sessions (vital sign recording), but only 45% for using messaging or FaceTime. The THMP group had a lower 90-day readmission rate compared to SOC (28% vs 58%; P = 0.004). The THMP cohort also showed improved QOL in regards to physical function (P = 0.02) and general health (P = 0.05) at 90 days.To our knowledge, this is the first RCT demonstrating the impact of THMP after LT. The magnitude of effect on LT outcomes, hospital readmissions, and QOL suggests that the adoption of telemedicine has great potential for other major operations.

Given the current climate of drug shortages in the United States, this review summarizes available comparative literature on the use of alternative immunosuppressive agents in adult solid organ transplant recipients including kidney, pancreas, liver, lung, and heart, when immediate-release tacrolimus (IR-TAC) is not available. Alternative options explored include extended-release tacrolimus (ER-TAC) formulations, cyclosporine, belatacept, mammalian target of rapamycin inhibitors, and novel uses of induction therapy for maintenance immunosuppression. Of available alternatives, only ER-TAC formulations are of non-inferior efficacy compared to IR-TAC when used de novo or after conversion in stable kidney transplant recipients (KTRs). All other alternatives were associated with higher rates of biopsy-proven rejection, but improved tolerance from classic adverse effects of IR-TAC including nephrotoxicity and development of diabetes. While most alternative therapies are approved in KTRs, access via third-party payors is an obstacle in non-KTRs. In the setting of IR-TAC shortage, alternate therapeutic options may be plausible depending on the organ population and individual patient situation to ensure appropriate, effective immunosuppression for each patient.

Breakthroughs in Hepatitis C virus (HCV) treatment and rising rates of intravenous drug use have led to an increase in the number of organ donors that are HCV antibody positive but serum nucleic acid test (NAT) negative. The risk of HCV transmission from the liver grafts of these donors to recipients is unknown. To estimate the incidence of HCV transmission, we prospectively followed 26 consecutive HCV antibody (n=25) or NAT (n =1) negative transplant recipients who received a liver graft from donors that were HCV antibody positive but serum NAT negative between March 2016 and March 2017. HCV transmission was considered to have occurred if recipients exhibited a positive HCV-polymerase chain reaction test by 3 months following transplantation. Drug overdose was listed as the cause of death in 15 (60%) of the donors. One recipient died eighteen days after transplantation from primary graft non-function and was excluded. Of the remaining 25 recipients, HCV transmission occurred in 4 (16%), at a median follow up of 11 months, all from donors who died of drug overdose. Three of these patients were treated with direct acting antiviral therapy, with two achieving a sustained virologic response and one an end-of-treatment response. One patient with HCV transmission died after a complicated post-operative course and did not receive antiviral therapy. Conclusions: In this prospective cohort of non-HCV liver recipients receiving grafts from HCV antibody positive/NAT negative donors, the incidence of HCV transmission was 16%, with the highest risk conferred by donors who died of drug overdose. Given the availability of safe and highly effective antiviral therapies, use of such organs could be considered to expand the donor pool. This article is protected by copyright. All rights reserved.

The availability of direct-acting antiviral agents for the treatment of hepatitis C virus (HCV) infection has resulted in a profound shift in the approach to the management of this infection. These changes have affected the practice of solid organ transplantation by altering the framework by which patients with end-stage organ disease are managed and receive organ transplants. The high level of safety and efficacy of these medications in patients with chronic HCV infection provides the opportunity to explore their use in the setting of transplanting organs from HCV-viremic patients into non-HCV-viremic recipients. Because these organs are frequently discarded and typically come from younger donors, this approach has the potential to save lives on the solid organ transplant waitlist. Therefore, an urgent need exists for prospective research protocols that study the risk versus benefit of using organs for hepatitis C-infected donors. In response to this rapidly changing practice and the need for scientific study and consensus, the American Society of Transplantation convened a meeting of experts to review current data and develop the framework for the study of using HCV viremic organs in solid organ transplantation.

Obesity has become an epidemic in the United States over the past decade, and recent studies have shown this trend in the liver transplantation (LT) population. These patients may be candidates for laparoscopic sleeve gastrectomy (LSG) to promote significant and sustained weight loss to prevent recurrence of nonalcoholic steatohepatitis. However, safety remains a concern, and efficacy in this setting is uncertain. A single-institution database from 2014 to 2018 was queried for patients undergoing LSG following LT. The selection criteria for surgery were consistent with National Institutes of Health guidelines, and patients were at least 6 months after LT. A total of 15 patients (median age, 59.0 years; Caucasian, 86.7%; and female, 60%) underwent LSG following LT. Median time from LT to LSG was 2.2 years with a median follow-up period of 2.6 years. The median hospital length of stay (LOS) was 2 days after LSG. Mortality and rate of liver allograft rejection was 0, and there was 1 postoperative complication (a surgical site infection). Following LSG, body mass index (BMI) decreased from 42.7 to 35.9 kg/m2 (P < 0.01), and in 12 patients with at least 1 year of follow-up, the total body weight loss was 20.6%. Following LSG in patients with diabetes, the median daily insulin requirements decreased from 98 (49-118) to 0 (0-29) units/day (P = 0.02), and 60% discontinued insulin. Post-LT patients had a similar decrease in BMI and reduction in comorbidities at 1 year compared with a matched non-LT patient cohort. In the largest patient series to date, we show that LSG following LT is safe, effective, and does not increase the incidence of liver allograft rejection. Larger longer-term studies are needed to confirm underlying metabolic changes following LSG.

Background In this observational study, we analyzed the feasibility and early results of a perioperative, video-based educational program and tele-health home monitoring model on postoperative care management and readmissions for patients undergoing liver transplantation. Methods Twenty consecutive liver transplantation recipients were provided with tele-health home monitoring and an educational video program during the perioperative period. Vital statistics were tracked and monitored daily with emphasis placed on readings outside of the normal range (threshold violations). Additionally, responses to effectiveness questionnaires were collected retrospectively for analysis. Results In the study, 19 of the 20 patients responded to the effectiveness questionnaire, with 95% reporting having watched all 10 videos, 68% watching some more than once, and 100% finding them effective in improving their preparedness for understanding their postoperative care. Among these 20 patients, there was an observed 19% threshold violation rate for systolic blood pressure, 6% threshold violation rate for mean blood glucose concentrations, and 8% threshold violation rate for mean weights. This subset of patients had a 90-day readmission rate of 30%. Conclusion This observational study demonstrates that tele-health home monitoring and video-based educational programs are feasible in liver transplantation recipients and seem to be effective in enhancing the monitoring of vital statistics postoperatively. These data suggest that smart technology is effective in creating a greater awareness and understanding of how to manage postoperative care after liver transplantation.

Context: Obesity has been reported as risk factor for reduced posttransplant graft and patient survival and increased delayed graft function (DGF). Objective: The purpose of this work is to analyze the effect of body mass index (BMI) on defined transplant outcomes in patients transplanted under defined guidelines in a kidney transplant program. Design: Review of a prospectively collected database in renal transplant recipients receiving rabbit antithymocyte globulin induction, mycophenolate mofetil, tacrolimus, and early corticosteroid withdrawal between 2001 and 2011. Setting: This review was conducted in a single abdominal transplant program in the United States. Main Outcome Measures: Primary outcome was death-censored graft survival categorized by posttransplant body mass groups. Secondary outcomes included DGF as well as patient survival. Results: Four hundred sixty seven patients were identified. No difference was observed in graft survival or DGF between BMI groups. One-year, death-censored graft survival and patient survival rates ranged from 97.5% to 100% and 96.6% to 100%, respectively. Delayed graft function was uncommon across all BMI groups, ranging from 5.3% to 9.1%, with the lowest incidence in patients with a BMI ≥ 35 kg/m2. Biopsy-proven acute rejection rates at 1 year were similar across all groups (10.1%-14%) as were estimated glomerular filtration rates were at 1, 3, and 5 years. Conclusion: Our results do not show an effect of BMI on posttransplant outcomes, suggesting that relaxation of BMI criteria may be warranted for recipient selection.

Hepatitis C (HCV) disease transmission from the use of HCV antibody-positive and HCV nucleic acid test-negative (HCV Ab+/NAT-) kidneys have been anecdotally reported to be absent. We prospectively analyzed kidney transplant (KT) outcomes from HCV Ab+/NAT- donors to HCV naive recipients under T-cell depleting early steroid withdrawal immunosuppression. Allografts from 40 HCV Ab+/NAT- donors were transplanted to 52 HCV Ab- recipients between July 2016 and February 2018. Thirty-three (82.5%) of donors met Public Health Service (PHS) increased risk criteria. De novo HCV infection was detected at 3 months post-KT in one recipient (1.9%). This was a case of transmission from a HCV Ab+ NAT+ donor with an initial false-negative NAT completed using sample collected on donor hospital admission (day 2). At the time of HCV diagnosis, a stored donor sample collected during procurement (day 4) was tested and resulted NAT-positive. Subsequently, sustained virologic response (SVR) was achieved with 12 weeks of glecaprevir/pibrentasvir. One death with functioning graft at 261 days post-KT was determined not related to HCV or donor factors. This experience provides evidence of a low transmission rate of HCV from HCV Ab+/ NAT- kidney donors, thereby arguing for increasing utilization.

Background Given the shortage of available liver grafts, transplantation (LTx) of hepatitis C virus antibody-positive, nucleic acid test-negative (HCV Ab+/NAT-) livers into nonviremic HCV recipients can expand the donor pool. Having previously described the sentinel experience of HCV Ab+/NAT- allografts in nonviremic recipients, we report the growth and extended follow-up of this program for 55 patients compared with recipients of Public Health Services (PHS) increased-risk donor HCV Ab-/NAT- allografts. Study Design A prospective review of all HCV nonviremic LTx patients receiving HCV Ab+/NAT- organs between March 2016 and August 2018 was performed. All HCV Ab+/NAT- organ recipients underwent HCV testing at 3 months and 1-year post-LTx to determine HCV transmission. Results Fifty-five HCV nonviremic candidates received HCV Ab+/NAT- organs; 64% male, median age 59 years (range 36 to 69 years) and median Model for End-Stage Liver Disease score of 22.5. Two recipients were excluded due to death before HCV testing. The HCV disease transmission occurred in 5 recipients (9%). Of these, 4 (80%) underwent anti-HCV treatment with eradication of virus. No patient found to be negative at 3 months seroconverted at 1-year follow-up. No patients who received PHS increased-risk donor HCV Ab-/NAT- organs had viremia develop (0 of 57) and there was no difference in graft and renal function, complications, or survival between HCV Ab+/NAT- recipients and PHS increased-risk donor HCV Ab-/NAT- recipients. Conclusions We report the largest experience with LTx from HCV Ab+/NAT- donors into 55 seronegative recipients with a HCV transmission rate of 9% with no late conversions at 1 year and no difference in function or graft loss compared with PHS increased-risk donor HCV Ab-/NAT- recipients. Due to availability of safe and effective HCV therapies, the use of such organs should be strongly considered to increase the donor organ pool.

Integration of pharmacists into multidisciplinary transplant patient care has advanced in recent years, with limited data available to evaluate the current status of the profession. This was a national survey developed as an AST Pharmacy COP initiative. Responses were solicited from pharmacists practicing at U.S. transplant programs based on UNOS listing; 176 participants from 113 centers (41%) responded, with 79% practicing ≤10 years. There is a median of 1.4 pharmacist full-time equivalents (FTEs) (range 0.1-7.1) for every 100 transplants. The predominant activities performed by pharmacists during the transplant phase include medication review (95%), lab review (92%), allergy review (88%), medication therapy management (92%), bedside rounds (87%), medication education (79%), documentation (71%), and coordinating discharge medications (58%). Similar activities were reported during the other phases, but participation was less common. The involvement of dedicated transplant pharmacists within multidisciplinary care has become standard at a large number of centers, although expansion is still needed to ensure core pharmaceutical care components are provided to all transplant recipients across all centers. These results inform on the typical responsibilities of pharmacists practicing within the field of transplantation and illustrate that the level of pharmacist involvement significantly varies across transplant centers and the phases of transplantation.

Following solid organ transplant, complex, lifelong medication regimens are required to prevent allograft rejection. Estimates of medication nonadherence in transplant recipients vary and may be as high as 70%. Poor medication adherence post transplant has been recognized as a contributing factor to reduced outcomes, including rejection, graft loss, and survival. Despite the numerous identified approaches for adherence assessment, there remains no gold standard. Ongoing efforts to identify optimal immunosuppressant adherence monitoring and measuring tools in an attempt to identify at risk populations post transplantation continue; however, the link between this information and outcomes remains to be discovered. Future adherence studies within the transplant population should focus on developing surrogate markers of immunosuppressant therapy adequacy and exploring the association amongst this data, adherence interventions, and outcomes so that optimal strategies may be identified. Immunosuppressant adherence should not be assumed, and interventions aimed a priori will provide opportunities to derail the movement of negative health outcomes resulting from preventable causes.

To evaluate the durability of the response to rifaximin for treatment of hepatic encephalopathy (HE).The nonsystemic antibiotic rifaximin has been approved for maintenance of HE remission, and several studies have indicated the efficacy of rifaximin for acute HE; however, the duration of therapeutic response for6 months remains unknown.Medical records of patients with cirrhosis who received rifaximin maintenance therapy for HE between January 2004 and May 2009 were reviewed. Model for end-stage liver disease (MELD) scores were obtained every 3 months during therapy.Of 203 patients with HE (Conn score ≥2), 149 received rifaximin monotherapy (400 to 1600 mg/d) and 54 received rifaximin (600 to 1200 mg/d) and lactulose (90 mL/d) dual therapy. Maintenance of HE remission for 1 year occurred in 81% and 67% of patients who received rifaximin monotherapy and rifaximin and lactulose dual therapy, respectively. Patient populations with a baseline mean MELD score ≤20 had few overt HE events, suggesting increased response to rifaximin in these patients.Rifaximin is effective for the management of HE in patients with cirrhosis, particularly in populations with MELD scores ≤20. Additional studies are needed to investigate the potential association between MELD scores and the efficacy of HE treatments.

Despite advances in the field of transplantation, immunosuppressant medication nonadherence (NA) remains a primary contributor to suboptimal long-term outcomes. Due to the multidimensional and multifactorial causes of medication NA, studies to date have focused on individual differing facets or single point barriers of NA with relative success. However, these successes have not proven to be sustainable, partly due to the intense resources needed for continued viability. This article provides a summary of a 2-day meeting held in April 2017 (Chicago, IL) prior to the American Transplant Congress in which a multidisciplinary group convened to identify the unmet research needs related to medication NA in transplantation. Thought leaders in the field presented the past, present, and future directions of medication NA with the primary outcome of designing, developing, and ranking targeted interventions into a dynamic research agenda to identify which interventions maintained effects over time. Break-out sessions were created based on the five World Health Organization (WHO) dimensions of adherence. Participants were then organized into the newly formed AST Transplant Pharmacy Adherence Consortium (AST TPAC) research group. This meeting report summarizes the content of the symposium, and the development, background, and future directions of the AST TPAC.

About 5,500 liver transplants are performed annually in the United States. The most common indication for liver failure resulting in liver transplantation is chronic hepatitis C virus (HCV). The management issues are complex, including universal HCV recurrence following transplantation, proper immunosuppression management, and morbidity and mortality issues. Treatment options with antiviral therapies have been minimally effective and are fraught with various drug-related side effects. Various outcomes exist for liver transplantation recipients with HCV recurrence. The side effects are numerous, particularly neutropenia, anemia, and depression, but are similar to the complications seen in the nontransplant community. This report discusses the current treatment options for liver transplant recipients with hepatitis C.

Previous data have suggested that the nonsystemic antibiotic rifaximin may be effective for the treatment of Clostridium difficile infection (CDI). This single-center retrospective study evaluated the efficacy of rifaximin for the treatment of CDI refractory to standard treatments in patients who had received liver transplants. Among 205 patients who had received liver transplants between July 2001 and December 2007, 3 patients with a confirmed diagnosis of C. difficile experienced recurrent diarrhea even though they received standard therapy. Patient 1, a 56-year-old male, patient 2, a 62-year-old male, and patient 3, a 73-year-old female, developed CDIs 190, 318, and 2310 days after transplantation, respectively. All patients experienced symptom recurrences after oral metronidazole therapy (250 mg 3 times daily for either 14 or 28 days) and after oral vancomycin therapy (125 mg 4 times daily for 14 days). Long-term vancomycin treatment (ie, 28 days) was required for patients 1 and 2. Vancomycin was discontinued in patient 3 because of increased creatinine levels. Oral rifaximin (400 mg 3 times daily) was initiated immediately after discontinuation of vancomycin therapy. Within 36 to 48 hours of the initiation of rifaximin treatment, diarrheal symptoms were resolved in all patients. After completing a 28-day course of rifaximin, patient 1 remained symptom-free during 185 days of follow-up, and patient 2 remained symptom-free during 250 days of follow-up. Patient 3 reported no symptoms within 155 days after the completion of rifaximin treatment. These findings suggest that rifaximin may be effective for the treatment of recurrent CDI and may provide a therapeutic option for CDI in immunocompromised patients.

Liver transplantation (LT) provides long-term survival for adults with end-stage liver disease. As a result of improved survival and an aging United States population the demand for LT in older patients is expected to increase. The aim of this study was to describe the transplantation trends in the older recipient (older than 65 years).Using the United Network for Organ Sharing database, we identified LT recipients between 1990 and 2006. We used Kaplan-Meier method to calculate overall survival (1, 3, 5 and 10 years) and Cox regression for predictors of survival.During the study period 5630 (7.6%) LT recipients were older than 65 years. There were 4256 (79.4%) whites, Hispanic (10.3%), African Americans (AA) (3.6%), and rest (6.7%). There was an increase in LT for older than 65 years from 4.1% in 1990 to 10.2% in 2006 (P=0.002) and a regional variation (P0.001). The 10-year patient and graft survival was 60% and 57% for less than 65 years versus 42% and 40% for more than 65 years (P0.0001). With age stratification (65-75 years vs.75 years), there was no difference in survival but when adjusted for race there was a significant difference in graft survival with a 10 year (white 40%, Hispanic 44%, and AA 19%) (P=0.04).The demand for LT in recipients older than 65 years is increasing. Although their survival is lower in comparison with recipients less than 65 years, there seems to be no difference in unadjusted survival with age stratification above 65 years. Among ethnic minorities, there was a disproportionately lower percentage of African Americans LT and a decreased survival.

Background Recent reports have documented ethnic disparity in access to health care. This disparity appears to exist in organ transplantation and the contributing factors include lack of insurance as well as poor socioeconomic status. The role of geographic location and ethnic composition on accessibility to liver transplantation (LT) is unclear. Therefore, the aim of this study was to determine ethnic transplantation trends based on United Network for Organ Sharing (UNOS) regions. Methods Using the UNOS database, we identified all adults (> or =18 years) that received LT between 2000 and 2005. We excluded multiorgan transplants and living donor transplantation. The data collected included ethnicity, transplantation rate, and UNOS region. Data were analyzed using the chi test. Results A total of 30,311 patients received a LT during the study period. Of these, 22,673 (74.8%) were white, 3621 (12%) were Hispanic, 2490 (8.2%) were African Americans, and the rest of other ethnic groups (5%). Liver transplantation based on ethnicity was region specific, with the lowest for African Americans in region 6 (2.7%), for Hispanics in region 11 (2.2%), and for whites in region 5 (57.6%), respectively. There was no consistent correlation between the ethnicity of the recipients and the ethnic composition of the geographic location (region). Conclusion Significant variations in access to liver transplantation for ethnic minorities exist across geographic lines. Understanding the interaction between ethnic minorities with end-stage liver disease in a geographic location and a transplant center will be invaluable as a first step in identifying the key nonmedical factors that play a role in this disparity.

Background: Cardiovascular disease (CVD) is the leading cause of death with a functioning graft in renal transplant recipients. The purpose of this study was to compare Framingham Risk Score (FRS), metabolic syndrome (MS), and cardiovascular events (CVE) in patients receiving early corticosteroid withdrawal (ECSWD), or chronic corticosteroid therapy (CCS). Methods: In all, 251 ECSWD and 146 CCS patients were evaluated. FRS and MS were identified at baseline, six, 12, and 24 months post-transplant. A total of 124 patients with diabetes mellitus prior to transplantation were excluded from MS analysis. CVE were defined as sudden-death, MI, angina, or CVA/TIA. Repeat-measure logistic regression was used for statistical analysis. Results: Fifty-four patients experienced 72 CVE. Mean follow-up was 755 ± 312 d and time to CVE was 14.8 ± 8.3 months. Demographics were similar between groups. FRS was not different between groups. CVE were significantly greater in CCS patients then ECSWD (20% vs. 10%, p = 0.024). New-onset MS occurred more frequently in patients receiving CCS then ECSWD (45% vs. 22%, p

Introduction: Conventional therapy to prevent HBV recurrence in liver transplant (LTx) recipients consists of Hepatitis B Immune Globulin (HBIg). The aim of this review is to investigate the safety and efficacy of converting HBIg and LAM therapy to ADV and LAM therapy. Methods: A retrospective review involving all liver transplant patients with HBV maintained on HBIg and LAM therapy. Results collected included: gender, age, HBV serological and DNA status (COBAS AmpliScreen PCR-based testing). Serologic testing was done every three months. Patients were followed for drug reactions, therapy compliance, and immune suppression compliance. A cost benefit analysis was done for drug comparisons using United States currency values. Results: Patient demographics included: Male (n=6), Female (n=4), mean age 44 years (range 33 to 65). The mean length of follow up since therapy conversion (from HBIg and LMV to ADV and LMV) was 21 months (range 16 to 25 months). Serological status at time of conversion revealed that DNA status remained negative in all patients, HBsAg negative in 10/10, HB eAg (+) (5/10) and HBeAb (+)(5/10). None of the patients experienced an increase in transaminases while on dual ADV and LAM therapy. All patients were maintained on immune suppression monotherapy (tacrolimus) at 7–9 ng/mL. All patients reported compliance with the dual therapy and that they experienced no drug related side effects. Mean yearly costs for ADV and LAM was 7,235.00 United States dollars (range 6,550.00 to 8,225.00); while mean monthly costs for HBIg and LAM; 9225.00 (range 7205.00 to 12005.00). Conclusion: The above results demonstrate beneficial effects of ADV and LAM in place of the current standard of HBIg and LAM therapy. Safety and short term results show nucleoside therapy is adequate at preventing HBV viral recurrence. Lastly, the economic benefit for ADV and LAM vastly outweighed the HBIg and LAM group.

Advances in organ transplantation have led to improved graft and patient survival. Transplant pharmacist's education and training uniquely position them to contribute knowledge and skills to the management of these highly complex patients. In 2004, the United Network for Organ Sharing bylaws added requirements that all transplant programs identify one or more pharmacists with experience in transplant pharmacotherapy to be responsible for providing pharmaceutical care to solid organ transplant recipients. These bylaws also delineated the transplant pharmacist's roles and responsibilities. To further support these efforts, in 2007 the Centers for Medicare and Medicaid Services accreditation standards for transplant centers also mandated that a center have a designated, qualified expert in transplant pharmacology as a multidisciplinary team member. The transplant pharmacist is a consistent member of the transplant team that can add value to the multidisciplinary approach of prevention and treatment of transplant infectious diseases through all phases of transplant care.

Background Severe obesity has been shown to limit access to renal transplantation in patients with end stage renal disease (ESRD). Laparoscopic sleeve gastrectomy (LSG) has been performed in the ESRD population to assist in achieving waitlist and transplant eligibility. Little is known about how LSG impacts the bioequivalence tacrolimus products and immunosuppression pharmacokinetics. Methods This was a prospective, open-label, single-dose, crossover, two-period pharmacokinetic (PK) study. The purpose of this study was to assess single-dose PK of immediate-release tacrolimus (IR-TAC), extended-release tacrolimus (ER-TAC), and mycophenolic acid (MPA) in adult ESRD patients post-LSG. Results Twenty-three subjects were included in the 24-hour PK assessments. The ratio of geometric means between ER-TAC and IR-TAC was 103.5% (90% CI 89.6 – 119.6%) for AUC0-24 and 92.5% (90% CI 80.4 – 106.4%) for Cmax. PK parameters were similar between ER-TAC and IR-TAC, except for Cmin (p=0.004) and Cmax (p=0.04). MPA AUC0-24 was similar when given with either ER-TAC or IR-TAC (p=0.32). Patients expressing CYP3A5*1 genotypes had lower tacrolimus AUC0-24 values versus those with CYP3A5*3/*3 (IR-TAC p

Summary The aim of this study was to analyze the impact of morbid obesity in recipients on peritransplant resource utilization and survival outcomes. Using a linkage between the University HealthSystem Consortium and Scientific Registry of Transplant Recipients databases, we identified 12 445 patients who underwent liver transplantation (LT) between 2007 and 2011 and divided them into two cohorts based on recipient body mass index (BMI

Alpha-1-antitrypsin deficiency (AAT) is the most common inherited metabolic disease leading to liver transplantation (LT) in children and adults. The aim of the study was to determine transplantation trends and survival of LT recipients with AAT. Using the UNOS (United Network for Organ Sharing) database, we identified 567 patients who underwent LT and 3 who received lung and LT from 1995 to 2004. AAT accounted for 1.06% of all adult LTs and 3.51% for pediatric LT. The 1-, 3-, and 5-year patient survival was 89%, 85%, and 83%, respectively, for adults versus 92%, 90%, and 90% for pediatric patients (P = .04), and graft survival was 83%, 79%, and 77% for adults versus 84%, 81%, and 78% for pediatric patients (P = .51). By regression analysis, age was the only predictor for patient survival (P = .04). In conclusion, adult and pediatric LT recipients with AAT are predominantly of Caucasian ethnicity and have an excellent post-LT survival.

The reported patient and graft survivals among adults post-orthotopic liver transplantation (OLT) are variable, with an apparent discrepancy between ethnic groups. The aim of this study was to evaluate the impact of ethnicity on patient and graft survivals among adult and pediatric patients.A retrospective analysis from the UNOS/OPTN databank between January 1995 and December 2006 was performed on adult and pediatric liver transplant recipients. Patients were divided into 4 groups based on ethnicity: African Americans, Hispanic, Caucasians, and other. Kaplan-Meier (KM) analysis was used to calculate patient and graft survival. Log-rank tests were used to compare survival rates between groups.In our study 42,710 OLT patients were included in the analysis, 90% of whom were adults. Of the 38,639 adult recipients, 29,432 (76.1%) were Caucasian, 4369 (11.3%) were Hispanic, 2963 (7.7%) were African American, and the remaining 1875 (4.9%) were of other ethnicities. KM estimates and Cox regression analyses demonstrated that there was a significant ethnic difference in both patient and graft survivals at 1, 3, 5, and 10 years. African Americans showed a lower rate (P.001). Of the 4341 pediatric recipients, 2461 (56.7%) were Caucasian, 797 (18.4%) were Hispanic, 824 (18.9%) were African American, and the remaining 259 (5.9%) were of other ethnicities. Unlike the adults, there were no significant differences among ethnic groups in terms of patient (P=.31) and graft (P=.33) survival at 1, 3, 5, and 10 years after OLT.These results showed that adult African American OLT patients have a reduced transplantation rate and a worse survival rate when compared with other ethnicities in the adult but not in the pediatric population. This information suggests that further studies are indicated to identify the causes of racial differences in transplant access and outcomes in the adult patient population.

Background: Preventable readmissions have become a focal point for controlling cost and improving quality in medicine. The frequency and causes of readmissions after liver transplantation (OLT) at 30 days and 1 year have not been described. We aimed to determine the risk factors, rate, and outcomes of readmissions within the first year after OLT and its potential impact on patient and graft survival. Methods: Medical records of 239 consecutive patients who underwent OLT from 2007 to 2012 at University of Cincinnati Medical Center were reviewed. Fifteen patients were excluded owing to death (n = 11) or retransplantation (n = 4) within the same hospital stay. Transplant- and non-transplant-related factors were collected during the index admissions and potential readmissions. This database was then linked to the Scientific Registry of Transplant Recipients to link donor- and recipient-related data. Results: One hundred fifty-four patients (69%) were readmitted within 1 year after OLT, for a total of 413 readmissions (average, 2.7 readmissions per patient) and a median hospital length of stay of 4 days. There were 118 readmissions within the first 30 days in 41% of patients (92/224). Sixty-five percent of patients readmitted within 30 days after discharge (69/92) were hospitalized again at least once within the year. Twenty-nine percent of patients (64/224) were discharged to a rehabilitation center after OLT; if discharged to a rehabilitation center, these patients had a 53% and 81% risk of readmission in 30 days and 1 year, respectively, compared with patients discharged home (36% and 64%, respectively; P = .02). The most common reasons for readmission within the first 30 days after discharge were infection (19.5%), renal insufficiency (9.3%), vomiting/diarrhea (8.5%), and pulmonary edema/effusion (7.6%). The most common reasons for readmission after 1 month were infection (24.8%), acute cellular rejection (8.5%), and biliary complications (7.1%). Risk factors for readmission included presence of diabetes (odds ratio [OR], 2.3; 95% CI, 1.2-4.6) and albumin

The purpose of this study was to assess the incidence of Clostridium difficile infection in patients who received rifaximin for the treatment of hepatic encephalopathy (HE).Medical charts of patients who received rifaximin for the treatment of HE were reviewed. The number of patients who developed diarrhea during treatment with rifaximin and results of latex agglutination assays to detect C. difficile in stool samples were analyzed.A total of 211 patients received rifaximin for HE. Of these, 152 were treated in a university practice and 59 were treated in community practices. The mean dose of rifaximin was 1055 mg/d (range, 600 to 1600 mg/d) for a mean duration of 250 days (range, 180 to 385 d). Eighteen patients developed diarrhea during rifaximin treatment. None of these patients tested positive for C. difficile.This study demonstrates that treatment of HE with the safe, nonsystemic, gut-selective antibiotic rifaximin was not associated with the development of C. difficile infection.

Transplant pharmacists have been recognized as an essential part of the transplant team by their colleagues along with several governing and professional organizations. The specific education, training and responsibilities of the transplant pharmacist have not been clearly delineated in the literature. Various pharmacists across the country have been called upon to serve on the transplant team necessitating standardization of their fundamental and desirable activities. Therefore, the purpose of this manuscript is to describe the training and role of a transplant pharmacist on the patient care team and provide a roadmap to implementation of novel transplant pharmacy services.

Current CDC/USPHS screening threshold of 2% for prevalence of chronic HBV is “costeffective.” Screening US adults in lower prevalence populations (eg, as low as 0.3%) also is likely to be cost-effective, suggesting that current health policy should be reconsidered.

Factors contributing to inequitable access to liver transplantation include socioeconomic status, geographic location, and delayed referral. The aim of this study is to identify the factors associated with a high MELD at the time of listing. Using the UNOS database, we identified all adults listed from 2002 to 2006. Data collected included demographics, insurance payor (private and government, i.e., Medicaid and non-Medicaid), diagnosis, and MELD score categorized as low (20) and high (or=20). The results obtained show that a high MELD was associated with age, ethnicity, and insurance (P0.001). By multivariate analysis, insurance (OR = 1.21, 95% CI = 1.13-1.30, P0.001) and ethnicity (OR = 1.55, 95% CI = 1.28-1.88, P0.001) were independently associated with high MELD. In conclusion, ethnic minorities and liver transplant candidates with Medicaid are more likely to have a high MELD score at initial listing. The above results suggest that the type of insurance and ethnicity are independently associated with a high MELD (i.e., sicker patients).

Cardiovascular disease (CVD) is the leading cause of death with a functioning graft in renal transplant recipients. The purpose of this study was to compare Framingham Risk Score (FRS), metabolic syndrome (MS), and cardiovascular events (CVE) in patients receiving early corticosteroid withdrawal (ECSWD), or chronic corticosteroid therapy (CCS).In all, 251 ECSWD and 146 CCS patients were evaluated. FRS and MS were identified at baseline, six, 12, and 24 months post-transplant. A total of 124 patients with diabetes mellitus prior to transplantation were excluded from MS analysis. CVE were defined as sudden-death, MI, angina, or CVA/TIA. Repeat-measure logistic regression was used for statistical analysis.Fifty-four patients experienced 72 CVE. Mean follow-up was 755 +/- 312 d and time to CVE was 14.8 +/- 8.3 months. Demographics were similar between groups. FRS was not different between groups. CVE were significantly greater in CCS patients then ECSWD (20% vs. 10%, p = 0.024). New-onset MS occurred more frequently in patients receiving CCS then ECSWD (45% vs. 22%, p0.001) and was associated with more CVE (p0.015).Patients receiving ECSWD regimens have significantly decreased CVE and new onset MS compared with CCS. MS is associated with increased CV risk and CVE.

Liver transplantation (LT) as a treatment for Hepatocellular Carcinoma (HCC) provides excellent outcomes if restricted to patients who meet the Milan criteria (MC). The aim of this study was to evaluate the influence of ethnicity on eligibility for LT based on the MC. This is a retrospective cohort study of patients diagnosed with HCC at our institution between January 2000 and September 2005. We identified 169 patients, of whom 135 were male (80%), 108 were Caucasian (64%), 29% were African American (AA) and 7% were of other ethnicity. Eighty two patients (49%) met the MC at diagnosis. Age, gender, severity of liver disease or insurance status was not predictive of meeting MC at diagnosis. Ethnicity was the only significant predictor for failure to meet MC. Significantly fewer Caucasians exceeded the MC compared to AA (44 vs. 71%; P = 0.0015). Conclusion AA are more likely to present with HCC that exceeds the MC.

What Is the Innovation? Liver transplantation is a highly complex and resource-intense intervention. Patients are often significantly debilitated, have a poor nutritional state, and incur the comorbidities of chronic immunosuppression. These realities leave recipients at high risk for complicationsandsubsequent rehospitalization.Atour institution, the30day readmission rate following liver transplantation is 42% and increases to69%at 1 year.1 This rate is similar tonational 30-day readmission rates of 40%, andmore than 20%of these patients are readmittedmultiple times, with readmissions accounting formore than 10% of combined 90-day direct costs.2 Clearly, this is an area in which we as a community must improve. To address this issue, we are currently piloting a patientcentricmodelofacuteposttransplantationsurgical andmedical care. Throughatablet-basedmonitoringandfeedback infrastructure, telehealth will be used to support patients and caregivers and to improve their communication with health care professionals. Although use of telehealth has gained momentum in the medical community, it has not yet been well adopted in the surgical community. Duringthedevelopmental stage,asurveywasconductedamong transplantation candidates toassess technological literacy andwillingness to adopt a tablet monitoring system into their postoperative care. In total, 159 surveyswerecollected,withmostpatients reportinguseof the Internet (70.8%)andemail (73.8%),while almost half of the patients (45.6%) reported having used a smartphone or tablet computer. Almost 90%of patients reported being comfortableusingelectronicmonitoringandcommunicationduringtheposttransplantation period. In addition, 77.1% of patients thought that it would be helpful for postoperative care. Eligiblepatientsareenrolledat thetimeof transplantsurgeryadmission. On discharge, patients receive a tablet containing automatedtextmessagesspecifictotheirpostoperativestatus,dailyhealth questions, anda configuredvital sign trackingprogram fromremote devices to include temperature, bloodpressure, bloodglucose level, and weight measurements. The tablets are also equipped with videoconferencing ability to allow for patient and health care professional interface (Figure). Objectivemeasures, including alerts, timeliness of responses, and data inputs, are tracked by the transplant team.Thisprotocol isdesignedtoaddressacutepostoperativeneeds after transplantation, andpatientswill participate for90days.Using thesedata,thetransplantteamwillbeabletocloselymonitortheprogress of the recipients during their initial at-home days. In addition to reported patient data, health services utilization is tracked, including calls, clinic visits, and health care professional satisfaction.This informationwill beusedtoevaluate the impact that suchaprogramwillhaveonresourceutilizationandpatientandcaregiver satisfaction. Long-termendpoints of analysiswill include 30day and 90-day readmission rates, outpatient clinic visits, and recipient health metrics such as blood glucose level, blood pressure control,medicationadherence,weight lossorgain,andactivitygoals. The pilot study has successfully enrolled 20 of 23 eligible patients.Threepatientswerenotenrolleddue todeath, refusal, or lack of long-termevolution coverage at the place of residence. Because of theongoingnatureof thispilot study,preliminarydataarenotyet available but are expected by the fall of 2015.

The current United Network for Organ Sharing (UNOS) criteria for liver transplantation gives priority to patients with elevated serum alpha-fetoprotein (AFP; > or = 500 ng/mL) in the absence of radiologic evidence of a hepatic mass. Reports have shown that an elevated serum AFP is a poor diagnostic indicator for hepatocellular carcinoma (HCC) in patients with cirrhosis. Our aim was to determine if an AFP level above 500 ng/mL, in the absence of a liver mass by imaging study, correlates with the presence of HCC. Using the UNOS database we identified all patients transplanted for HCC in the United States between February 2002 and October 2005 based on these criteria. The data collected included: patient demographics, clinical information, and pathological outcomes. The data was analyzed using a chi-squared t-test and confirmed by logistic regression modeling. A total of 22 patients received a cadaveric liver transplant, while 1 received a living donor transplant during the study period. HCC was confirmed posttransplantation in only 6 patients (26%). There was no difference in race, gender, etiology of liver disease, or AFP level between patients with and without HCC but a significant difference in age (59.8 yr for HCC patients vs. 51.3 yr for the non-HCC group; P = 0.01). In conclusion, the majority of the patients who received extra Model for End-Stage Liver Disease (MELD) points based on an elevated AFP did not have HCC. Older age was a significant predictor for the presence of HCC in patients with a serum AFP greater than 500 ng/mL. These results demonstrate the poor correlation of serum AFP with the presence of HCC in patients awaiting liver transplantation.

Patients with end-stage liver disease often develop hepatic encephalopathy. The loss in cognitive abilities results in marked economic loss to the patient and health care community. We report hospital admission rates and economic impact of patients with end-stage liver disease suffering from hepatic encephalopathy.The medical records were reviewed involving liver transplant patients started on lactulose or rifaximin therapy after presenting with stage 2 hepatic encephalopathy from January 2004 to November 2005. Information collected included demographics, hospitalizations required for hepatic encephalopathy, economic data, and Model for End-stage Liver Disease (MELD) score.Thirty-nine patients met study criteria: 24 patients treated with lactulose (group one) and 15 with rifaximin (group two). Group one included 18 men and six women of mean age 48 (range 39 to 58), average MELD 14 (range 10 to 19). Group two included 10 men and five women of mean age 47 (range 42 to 58), average MELD 15 (range 10 to 19). Group one patients required 19 hospitalizations overall: three patients with three hospitalizations, four patients with two hospitalizations, and two patients required one hospitalization. Total drug cost per month was 50 dollars(group one) and 620 dollars(group two). The average annual cost of hospitalization, emergency room visit, and drug per patient treated was 13,284.96 dollars for a total of 318,839 dollars (range 5005 dollars to 26,255 dollars, including drug cost and hospital care). Group two required three hospitalizations, all three with one visit. The average annual cost of hospitalization, emergency room visit, and drug per patient treated was 7958.13 dollars for a total of 119,372 dollars (range 6005 dollars to 19,255 dollars, including drug cost and hospital care). The total cost of therapy per patient per year was 13,285 dollars (group one) versus 7958 dollars (group two). The average length of stay was shorter in group two [3.5 days (range 3 to 4)] versus group 1 [5.0 days (range 3 to 10); P.0001].These pilot data demonstrate the marked difference in economic costs for the treatment of hepatic encephalopathy. The results also show that in comparative groups, the economic gains are quickly lost when using lactulose.