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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.

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.

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.

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.

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.

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.

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.

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.