Function In Liver Transplant Recipients Research Articles

Vascular Dysfunction and Inflammation in Liver Transplant Recipients

INTRODUCTION Liver transplant (LT) recipients have an increased risk of developing cardiovascular disease (CVD) after transplant. The physiological mechanisms driving this risk are not fully understood. Vascular endothelial dysfunction is the initial pathophysiological step in the development of atherosclerosis. The objective of this study was to characterize vascular endothelial function in LT recipients. It was hypothesized that compared to matched healthy controls (HC), LT recipients would have impaired vascular function. METHODS. Conduit artery endothelial function was measured by flow-mediated dilation of the brachial artery (FMDBA) with duplex ultrasound in 40 LT patients (18 male, 22 female; mean ± SD: Age, 56±11 years) and 10 age matched HC (4 male, 6 female; Age 51±16 years). Central aortic blood pressures were derived from radial arterial tonometry and the use of the generalized transfer function. A venous blood sample was obtained for nuclear magnetic resonance spectroscopy assessment of the inflammation biomarker GlycA, and high-density lipoprotein (HDL) particle subspecies. A novel metabolic inflammation index was derived from plasma GlycA and HDL subparticle concentrations. RESULTS. LT recipients had higher peripheral (Median [IQR]: HC vs. LT, 119 [111-136] vs. 135 [124-147] mmHg, p=0.01) and central aortic (113 [102-126] vs. 124 [116-139] mmHg, p=0.03) systolic blood pressures. LT recipients had impaired vascular endothelial function (HC vs. LT, FMDBA: 6.08 [5.01-7.61] vs. 4.54 [3.31-6.24] %, p = 0.04). In LT recipients, the inflammation index (55 [45-62] AU) was negatively associated with vascular endothelial function ( r=-0.4, p=0.03). CONCLUSIONS. Despite optimal pharmacological intervention, LT recipients had higher systolic blood pressures and worse vascular endothelial dysfunction compared to HC. In LT recipients, a higher inflammation index was associated with worse endothelial function, suggesting that chronic low-grade inflammation may partly contribute to endothelial dysfunction in this patient population. These findings provide support for the vascular endothelium as a potential therapeutic target to improve cardiovascular health in LT recipients. Supported by CTSA award No. UM1TR004360 from the National Center for Advancing Translational Sciences. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Influence of immunosuppressive drugs on natural killer cells in therapeutic drug exposure in liver transplantation.

Natural killer (NK) cells are enriched in the liver and are the main regulators in liver transplantation regarding rejection or tolerance, viral infection, or tumor recurrence. Immunosuppression consists of a triple drug standard regimen comprising tacrolimus (TAC) and corticosteroids (CS) with either mycophenolate mofetil (MMF) or sirolimus (SIR)/everolimus (EVE). The aim of this study was to evaluate the impact of trough levels of these regimens under clinical conditions and exposure on human NK-cell activity and function in order to better understand the antiviral and anti-tumor effects of mammalian target of rapamycin inhibitor (mTORI). Peripheral blood mononuclear cells (PBMCs) were collected from liver transplant recipients and healthy controls. Number and phenotypes of NK cells in vivo were analyzed by flow cytometry. In this study we simulated the immunosuppressive microenvironment in vitro. PBMCs were cultured at the clinically effective plasma concentration of drugs for 3 d to detect the effect of immunosuppressants on NK cells. Drug type and concentration: single drug [EVE, 5 ng/mL; SIR, 5 ng/mL; TAC, 5 ng/mL; cyclosporine A (CSA), 125 ng/mL; MMF, 15 µg/mL; CS, 0.5 µg/mL] and combined immunosuppressants (Group 1: TAC, 5 ng/mL + MMF, 15 µg/mL + CS, 0.5 µg/mL; Group 2: TAC, 5 ng/mL + SIR, 5 ng/mL + CS, 0.5 µg/mL; Group 3: TAC, 5 ng/mL + EVE, 5 ng/mL + CS, 0.5 µg/mL). In addition, NK cells were sorted from PBMCs and treated under the above conditions to detect NK cell killing function and RNA transcription characteristics. CS significantly impaired the cytolytic activity of NK cells, followed by MMF and SIR/EVE. CS and TAC/CSA significantly decreased the secretion of IFN-γ and CD107a. NK cell function in liver transplant recipients was most pronouncedly inhibited by a triple immunosuppressive regimen, with CS playing the most prominent role compared with the other drugs. The MMF-containing regimen demonstrated a significant increase in the expression of suppressive genes, especially of the Siglec7/9 family. The SIR group had stronger NK cell activity compared with that of the MMF group, although liver transplantation patients have lower NK cell activity and function. Despite an overall comparable immunosuppressive efficiency in terms of prevention of acute rejection, a mTORIs-including regimen might be considered as having less impact on NK cell function.

Echocardiographic assessment of cardiovascular function and clinical outcomes in liver transplant recipients.

Cardiovascular disease contributes to a high rate of morbidity and mortality after liver transplantation (LT). However, the progression of cardiac function and cardiac remodeling in LT recipients remains poorly understood. This study sought to evaluate the progression of cardiac function and structure in LT recipients and identify independent predictors of prognosis using echocardiography. From 2009 to 2019, 178 adult LT recipients at a tertiary academic transplant center were retrospectively studied. Transthoracic echocardiograms 1-year pre- and post-LT were assessed. Primary outcomes were progression of systolic and diastolic function. Secondary outcomes included left ventricular remodeling, all-cause mortality, and heart failure readmission post-LT. Subgroup analyzes were performed for etiology of native liver disease. A multivariable model was constructed to examine independent predictors of outcomes. Systolic function significantly worsened, with reduction in stroke volume (45-37ml/m2 , p<.001), left ventricular ejection fraction (LVEF) (65%-62%, p<.001) and cardiac index (3.00-2.60 L/min/m2 , p<.001). Conversely, there were significant improvements in diastolic indices, including tricuspid regurgitation Vmax (228-215cm/s, p=.017), left atrial volume index (LAVI) (32-26ml/m2 , p<.001) and right ventricular systolic pressure (RVSP) (31-28mmHg, p=.001). Additionally, patients had increased relative wall thickness (RWT) (p<.001) and decreased left ventricular end-diastolic dimension/body surface area (p<.001) post-LT. The independent predictors for all-cause mortality and heart failure were increased pre-LT mitral annular early diastolic velocity (HR 1.11, CI 1.02-1.22, p=.018), LAVI (HR 1.06, CI 1.02-1.11, p=.007) and decreased LVEF (HR .89, CI .82-.97, p=.006). The effect of non-alcoholic steatohepatitis on cardiovascular outcomes post-LT was largely comparable to that of Hepatitis B. This study showed reduced systolic and improved diastolic function in LT recipients and highlighted the utility of pre-LT echocardiogram in the prognostication and risk stratification of LT candidates.

Weight Gain, Fibroblast Growth Factor‐23, and Vascular Function in Liver Transplant Recipients

INTRODUCTIONLiver transplant (LT) recipients experience significant weight gain and an increased risk of cardiovascular disease (CVD) after transplant. The pathophysiology of this cardiometabolic burden is not fully understood. In the general population, weight gain and increased adiposity are associated with elevated circulating levels of fibroblast growth factor‐23 (FGF‐23). Increased FGF‐23 has been linked with CVD in other disease populations. This study tested the working hypothesis that weight gain after LT is associated withincreased levels of FGF‐23, that subsequently contribute to vascular dysfunction, an established precursor of CVD.METHODSWe enrolled 21 LT patients (M/F: 9/12; Mean ± SEM, Age: 55 ± 2 yrs) and 8 age matched healthy controls (HC; M/F: 2/6; 47 ± 6 yrs). Vascular endothelial function was assessed with flow‐mediated dilation (FMD) of the brachial artery using duplex ultrasound. Aortic pressure waves were synthesized from radial artery waveforms acquired by applanation tonometry and the use of a generalized transfer function. Serum levels of FGF‐23 were assessed by enzyme linked immunosorbent assay (ELISA).RESULTSHigher body mass index (BMI) values were reported in LT patients (37 ± 1 kg/m2) compared to HC (26 ± 1 kg/m2, p = &lt;0.001). Weight gain (BMI) was positively associated with serum FGF‐23 values (r = 0.5, p = 0.01). Central systolic pressures (125 ± 3 vs. 110 ± 6 mmHg, p = 0.01) and central pulse pressures (51 ± 4 vs. 39 ± 4 mmHg, p = 0.05) were higher in LT patients compared with controls. There was no difference in endothelial function (FMD) in LT patients (4.59 ± 0.55%) compared to their HC counterparts (6.08 ± 0.48%, p = 0.12). FGF‐23 values were not associated with measures of vascular function.CONCLUSIONWeight gain is evident in LT patients and is correlated with higher serum FGF‐23 values. However, our findings do not suggest a relationship between serum levels of FGF‐23 and vascular function in LT recipients.

Renal safety of tenofovir disoproxil fumarate and entecavir in liver transplant patients: a nationwide Korean registry study.

Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) have been recommended after liver transplantation to prevent recurrence of hepatitis B virus infection. Despite its proven efficacy, the renal safety of TDF has not been established in liver transplant recipients. We aimed to compare the effects of TDF and ETV on renal function in liver transplant recipients and to evaluate risk factors for renal dysfunction after liver transplantation. This is a retrospective, observational multicenter study of data from the Korean Organ Transplantation Registry. We included adults who underwent liver transplantation for hepatitis B virus-related complications from April 2014 to December 2017 and received TDF or ETV post-transplantation. Renal dysfunction was defined as an estimated glomerular filtration rate decline by at least 20% from baseline (1month post-transplantation). Median duration of follow-up was 29months (interquartile range 19-42). A total of 804 liver transplant patients were included. The cumulative probability of renal dysfunction was significantly higher in the TDF group than in the ETV group. Multivariable analysis confirmed that TDF was independently associated with an increased risk of renal dysfunction (hazard ratio = 1.47, 95% confidence interval 1.12-1.92; p = 0.005). Independent risk factors for renal dysfunction included older age, worse baseline renal function, and low body mass index. Overall survival rate was significantly lower in patients with renal dysfunction than in those without. In this nationwide study, the use of TDF was associated with an increased risk of renal dysfunction, when compared with ETV.

The effect of early everolimus administration on the renal function while reducing the dosage of calcineurin inhibitors in liver transplant recipients in a long-term follow-up

Introduction. The lifelong use of calcineurin inhibitors in liver transplant recipients leads to an increased incidence of chronic kidney disease.Objective. To compare the changes in glomerular filtration rate over five years in liver transplant recipients between those on everolimus with a reduced exposure to calcineurin inhibitors and those on standard doses of calcineurin inhibitors.Material and methods. Fourteen liver transplant recipient switched to everolimus with a minimization of calcineurin inhibitors exposure in the first months after liver transplantation from February 2009 to February 2015 who had received that therapy continuously for at least 60 months were included in the case-control study. Twenty eight liver transplant recipients (matched by sex, etiology of the underlying disease, calcineurin inhibitors) who were followed-up for at least 60 months after liver transplantation, who had received no dose of everolimus, in whom the glomerular filtration rate could be calculated at all points of analysis were selected as a comparison group (1:2). Glomerular filtration rate was calculated immediately before liver transplantation; 12, 24, 36, 48, and 60 months after liver transplantation. The glomerular filtration rate after liver transplantation was also calculated for liver transplant recipients from the main group immediately before the conversion to everolimus.Results. Before liver transplantation, the median of glomerular filtration rate in the main group of liver transplant recipients was lower (81.2 ml/min) than in the comparison group (97.5 ml/min, p=0.01). After liver transplantation, the renal function worsened in both groups of patients. In a pairwise comparison, the medians of glomerular filtration rate were statistically significantly lower after 12 months, 24 months, 36 months, 48 months after liver transplantation, than before liver transplantation. The median of glomerular filtration rate at the time of immunosuppression conversion was 44.3 ml/min. After the conversion of immunosuppression, the median of glomerular filtration rate gradually increased, and after 36 months the differences in glomerular filtration rate reached statistical significance compared with the level before conversion (69.4 ml/min;p=0.048). These differences still increased after 60 months after conversion (72.3 ml/min; p=0.041).Conclusion. Long-term administration of everolimus with minimization of calcineurin inhibitors exposure with the early conversion to this immunosuppression regime provides a steady improvement in renal function in liver transplant recipients with a low glomerular filtration rate in the preoperative and early post-transplant period.

Non-HLA Autoantibodies at 1 Year Negatively Affect 5-Year Native Renal Function in Liver Transplant Recipients

BackgroundAngiotensin II type-1 receptor (AT1R) and endothelin-1 type A receptor (ETAR) autoantibodies, in addition to allograft injury, can bind native endothelial cells and cause vascular vasoconstriction and fibrosis progression in nontransplanted organs. Therefore, we investigated long-term native renal function in liver transplant (LT) recipients with and without anti-AT1R-Abs and/or anti-ETAR-Abs present in serum. MethodsPrimary LT recipients at our single center from January 2000 to April 2009 had their prospectively collected pre-LT (1269 patients) and year 1 post-LT (795 patients) serum tested retrospectively for anti-AT1R-Abs and/or anti-ETAR-Abs. Anti-AT1R-Abs and anti-ETAR-Abs testing was accomplished with a standardized solid phase assay in which >10 U was considered positive. ResultsPretransplant anti-AT1R-Abs and/or anti-ETAR-Abs did not change the median delta creatinine from pretransplant to 1 year post-transplant. In multivariable analysis controlling for diabetes (DM) and calcineurin inhibitor (CNI) use, anti-AT1R-Abs and/or anti-ETAR-Abs at 1-year remained statistically significantly associated with a decline in GFR (measured by Modification of Diet in Renal Disease-6) from years 1-5 post-LT (P = .04). In diabetic patients the association with a decline in renal function was more pronounced with (-9.29 mL/min) vs without (-2.28 mL/min) anti-AT1R-Abs and/or anti-ETAR-Abs at year 1, respectively (P = .004). ConclusionAt 1-year post-LT, the autoantibodies anti-AT1R-Abs and/or anti-ETAR-Abs are associated in multivariable analysis with an increased risk of native renal function decline especially in diabetic patients.

Sorafenib for advanced hepatocellular carcinoma provides better prognosis after liver transplantation than without liver transplantation.

Although sorafenib has been used to treat advanced hepatocellular carcinoma (HCC), the efficacy of sorafenib in patients with recurrent HCCs after liver transplantation (LT) has not been compared with that in patients without LT (non-LT). Between 2008 and 2019, a total of 832 consecutive HCC patients treated with sorafenib (790 in the non-LT group and 42 in the LT group) were enrolled. The primary outcome was overall survival (OS). Secondary outcomes were time-to-progression (TTP), objective response rate (ORR) and disease control rate (DCR). Treatment outcomes were assessed by multiple subgroup analyses and propensity-score matching (PSM). The median follow-up duration was 152.5days. The LT group was younger and had smaller intrahepatic HCC than the non-LT group. The LT group showed significantly better OS (16.8 vs. 7.1months, p < 0.001), TTP, ORR and DCR than the non-LT group. The superior efficacy of sorafenib in the LT group was corroborated in multiple subgroup analyses stratified by metastasis, effective sorafenib maintenance dose, or Child-Turcotte-Pugh class A. LT was identified as an independent factor for favorable OS. Intrahepatic HCC was the strongest tumor-related factor for both OS and TTP and was significantly associated with tumor response and hepatic function. Finally, subanalyses including only patients with small intrahepatic HCC or PSM modeling showed no difference in sorafenib efficacy between the LT and the non-LT groups. Sorafenib provides better outcomes in the LT setting than the non-LT setting. This benefit may be associated with the smaller intrahepatic HCC coupled with preserved hepatic function in LT recipients.

Immune and gene expression profiling during tacrolimus to everolimus conversion early after liver transplantation

Early elimination of tacrolimus in favor of everolimus can improve renal function in liver transplant recipients. However, as this approach increases the risk of acute rejection, it may benefit from predictive biomarkers guiding weaning. We enrolled 20 recipients on stable tacrolimus + everolimus to undergo tacrolimus withdrawal early post-liver transplant. Blood samples were collected at month 3 (withdrawal initiation), 4 (withdrawal completion), 4.5 and 6 (both everolimus alone). 15 patients did not reject and 5 had mild rejection responding to tacrolimus resumption. Before tacrolimus withdrawal, eventual rejecters had higher percentages of CD56+ NK cells and CD19+CD27+CD24+ memory B cells, and lower levels of T cells expressing the exhaustion marker PD-1. Over time, memory B cells, Ki-67+CD3+ (proliferating) cells and CD4+CD127-CD25HIGH FOXP3+ Tregs increased in rejecters. Tregs also increased in non-rejecters over time. The number of differentially expressed genes progressively increased in rejecters, particularly in mTOR, Eukaryotic Initiation Factor 2, and Neuroinflammation signaling pathways. There was no difference in anti-HLA antibodies between the groups. In summary, blood mononuclear cell and gene expression may predict successful vs. failed early tacrolimus withdrawal in liver transplant recipients. While needing validation, these preliminary findings highlight the potential for cellular and molecular biomarkers to guide decision-making during tacrolimus weaning.

Time to Conversion to an Everolimus-Based Regimen: Renal Outcomes in Liver Transplant Recipients From the EVEROLIVER Registry.

Longterm use of a calcineurin inhibitor (CNI)-based regimen is one of the major reasons for chronic renal failure in liver transplantation recipients (LTRs). The Everolimus Liver registry (EVEROLIVER) evaluated renal function in LTRs who were converted to everolimus (EVR). This observational registry included all LTRs receiving EVR across 9 centers from France. Data are being collected in an electronic database over 10 years (12 visits/patient) to evaluate efficacy, renal function (estimated glomerular filtration rate [eGFR]), and safety of EVR use in clinical practice, and the current analysis is reporting up to 60months of findings. Until September 2017, 1045 patients received EVR after a mean time of 3.6±5.1years. CNI withdrawal was feasible in 57.7% of patients as of month 60. Mean eGFR improved in patients with baseline eGFR <60mL/minute/1.73m2 and was maintained in those with baseline eGFR ≥60mL/minute/1.73m2 . Among patients with chronic kidney disease (CKD; baseline eGFR <60mL/minute/1.73m2 ), 55% converted to EVR within 3 months (early conversion) and 39.4% converted between 4 and 12months after transplantation (mid-conversion) experienced improvement in eGFR (≥60mL/minute/1.73m2 ) at month 36. Only 20.9% and 17.4% among those converted beyond 12months (late conversion) experienced improvement respectively at month 36 and 60. A logistic regression analysis in patients with CKD stage ≥3 demonstrated that late conversion, age, and female sex were associated with nonimprovement of eGFR (≥60mL/minute/1.73m2 ). Data from this real-life use of EVR indicate that renal function was maintained from the preconversion period until month 36 even in patients with advanced CKD. However, early rather than late conversion appears to be a safe approach to preserve longterm renal function in LTRs.

Cognitive Function in Liver Transplant Recipients Who Survived More Than 6 Months.

Current research in the areas of liver transplant and cognitive function has primarily examined cognitive changes from pre- to 1-year posttransplant, resulting in an insufficient understanding of cognitive trajectory beyond early periods of transplant and its impact on self-management. This study aimed (1) to describe global and domain-specific cognitive function in liver transplant recipients who survived more than 6 months after transplant and (2) to describe patient and clinical characteristics of recipients with impaired global and/or domain-specific cognitive function. Further, this study explored the potential relationships between cognitive function and self-management by examining differences in cognitive function by levels of self-management. This secondary data analysis included 107 adult liver transplant recipients, who had a functioning transplant for at least 6 months. Data of cognitive function, demographic and clinical characteristics, and self-management were extracted for this study. T tests, Mann-Whitney tests, and Kruskal-Wallis tests were used to examine differences in cognitive function by variables. More than half of the recipients had global cognitive impairment. Significant differences were found in global and domain-specific cognitive function. Older, male, married, or deceased donor recipients had lower cognitive test scores than younger, female, single, or living donor recipients. There were no significant differences in global and domain-specific cognitive function by time since transplant and levels of self-management. Future longitudinal studies should examine the long-term trajectory of cognitive function posttransplant. Other factors such as caregivers' participation in self-management should be accounted for in future studies when examining the relationship between cognitive function and self-management.

Efficacy and safety of everolimus treatment on liver transplant recipients: A meta-analysis.

Everolimus is an effective immunosuppressant in organ transplantation without impaired renal function. The present study aimed to evaluate the efficacy and safety of everolimus therapy in liver transplant recipients. A systematic literature search was conducted to identify the eligible studies. The quality of the included studies was assessed. The outcomes of interest were biopsy-proven acute rejection (BPAR), graft loss, death, renal function and adverse events. Eight trials involving 1570 participants were included. Compared to the standard exposure to calcineurin inhibitors (CNIs), the incidences of BPAR, graft loss and death were not increased in the everolimus combined with reduced CNIs group. The renal function was significantly improved after everolimus combined with reduced CNI therapy, and the glomerular filtration rate (GFR) was estimated to be elevated by 5.59 (95% CI: 2.17-9.01, P=.001) as compared to the standard exposure to CNIs. The risk of any adverse event was increased by everolimus combined with reduced CNI therapy (RR=1.22, 95% CI: 1.04-1.42, P=.01) as compared to the standard exposure to CNIs. The likelihood of infection was not associated with the regimen. Any publication bias was not identified. Although everolimus combined with reduced CNI therapy significantly improved the renal function in liver transplant recipients, it did not influence the incidence of BPAR, graft loss and death. This regimen might be associated with an increased risk of adverse events, which needs to be elucidated further.

Preoperative echocardiographic evaluation of cardiac systolic and diastolic function in liver transplant recipients with diabetes mellitus: a propensity-score matched analysis.

BackgroundDiabetes mellitus (DM) increases risk of heart failure. It has been shown that diabetes leads to DM-cardiomyopathy, characterized by systolic and diastolic dysfunction. Pre-transplant diastolic dysfunction, has been associated with poor graft outcome and mortality. We assessed the hypothesis that end-stage liver disease (ESLD) patients with diabetes (DM-ESLD), have more advanced cardiac systolic and diastolic dysfunction, compared to ESLD patients without diabetes (Non DM-ESLD).MethodsWe retrospectively evaluated preoperative echocardiography of 1,319 consecutive liver transplant recipients (1,007 Non DM-ESLD vs. 312 DM-ESLD [23.7%]) January 2012–May 2016. Systolic and diastolic indices, such as left ventricular ejection fraction, transmital E/A ratio, tissue doppler s’, e’ velocity, and E/e’ ratio (index of left ventricular end-diastolic pressure), were compared using 1:2 propensity-score matching.ResultsDM-ESLD patients showed no differences in systolic indices of left ventricular ejection fraction and s’ velocity, whereas diastolic indices of E/A ratio ≤ 1 (49.0% vs. 40.2% P = 0.014), e’ velocity (median = 7.0 vs. 7.4 cm/s, P < 0.001) and E/e’ ratio (10.9 ± 3.2 vs. 10.1 ± 3.0, P < 0.001), showed worse diastolic function compare with Non DM-ESLD patients, respectively.ConclusionsDM-ESLD patients suffer higher degree of diastolic dysfunction compared with Non DM-ESLD patients. Based on this, careful preoperative screening for diastolic dysfunction in DM-ESLD patients is encouraged, because poor transplant outcomes have been noted in patients with preoperative diastolic dysfunction.

41. A Comparative Evaluation of MRI and Liver Biopsy for Liver Fat Estimation in Liver Transplant Donors

Background and Aims: Donor hepatic steatosis is associated with a greater risk of complications after living donor liver transplantation (LDLT). MRI IDEAL IQ (Iterative Decomposition of water and fat with Echo Asymmetry and Least squares estimation) has recently been shown to be accurate for hepatic fat quantification in animal and human studies. In this study, we describe the use of MRI IDEAL IQ technique in quantification of hepatic steatosis in live liver donors and compared it with liver biopsy. Methods: Between November 2014 to February 2017 we prospectively evaluated 50 liver donors comparing the MRI IDEAL IQ technique with either preoperative or intraoperative liver biopsy. The accuracy of MRI was assessed by linear regression analysis between MRI liver fat fraction and biopsy fat estimation. Results: Less than 3% fat content was detected in 33 donors (84.6%), 3–6% fat content in 13 (26%), 6–9% fat content in 3 (6%) and more than 9% fat content in 1 donor (2%) on MRI. On linear regression analysis MRI IDEAL IQ fat evaluation correlated well with histopathological fat evaluation for detecting fat content in livers (R2 = 0.757). The accuracy of MRI IDEAL IQ was 88% with sensitivity and specificity rates of 100% and 84.6% respectively for detecting fat content in the liver (P < 0.0001). The average liver fat content evaluated by MRI correlated with BMI but not with age or sex. The groups were comparable in terms of demographic and clinical variables in donors, or development of early graft dysfunction and deranged kidney function in liver transplant recipients. Conclusions: The MRI IDEAL IQ technique is a highly reliable and accurate method, which can replace liver biopsy for the liver fat estimation in live liver donors and hence avoid potential complications of an invasive biopsy. The authors have none to declare.

Sa1543 - Trend of Renal Function in Liver Transplant Recipients Treated for Chronic Hepatitis C Virus Infection with New Direct Acting Antiviral Agents

Sa1543 - Trend of Renal Function in Liver Transplant Recipients Treated for Chronic Hepatitis C Virus Infection with New Direct Acting Antiviral Agents

Impact of Sofosbuvir-Based Regimens for the Treatment of Hepatitis C After Liver Transplant on Renal Function: Results of a Canadian National Retrospective Study.

We assessed the impact of sofosbuvir-based regimens on renal function in liver transplant recipients with recurrent hepatitis C virus and the role of renal function on the efficacy and safety of these regimens. In an expanded pan-Canadian cohort, 180 liver transplant recipients were treated with sofosbuvir-based regimens for hepatitis C virus recurrence from January 2014 to May 2015. Mean age was 58 ± 6.85 years, and 50% had F3/4 fibrosis. Patients were stratified into 4 groups based on baseline estimated glomerular filtration rate (calculated by the Modification of Diet in Renal Disease formula): < 30, 30 to 45, 46 to 60, and > 60 mL/min/173 m2. The primary outcome was posttreatment changes in renal function from baseline. Secondary outcomes included sustained virologic response at 12 weeks posttreatment and anemia-related and serious adverse events. Posttreatment renal function was improved in most patients (58%). Renal function declined in 22% of patients, which was more marked in those with estimated glomerular filtration rate < 30 mL/min/173 m2, advanced cirrhosis (P = .05), and aggressive hepatitis C virus/fibrosing cholestatic hepatitis (P < .05). High rates (80%-88%) of sustained virologic response at 12 weeks posttreatment were seen across all renal function strata. Cirrhotic patients with glomerular filtration rates < 30 mL/min/173 m2 had sustained virologic response rates at 12 weeks posttreatment comparable to the overall patient group. Rates of anemia-related adverse events and transfusion requirements increased across decreasing estimated glomerular filtration rate groups, with notably more occurrences with ribavirin-based regimens. Sofosbuvir-based regimens improved overall renal function in liver transplant recipients, with sustained virologic response, suggesting an association of subclinical hepatitis C virus-related renal disease. Sustained virologic response rates at 12 weeks posttreatment (80%-88%) were comparable regardless of baseline renal function but lower in cirrhosis.

Impact of age on memory and executive function in liver transplant recipients

Impact of age on memory and executive function in liver transplant recipients

Everolimus with early withdrawal or reduced‐dose calcineurin inhibitors improves renal function in liver transplant recipients: A systematic review and meta‐analysis

Calcineurin inhibitors (CNI) are the mainstay of immunosuppression after liver transplantation (LT), but CNIs are associated with significant nephrotoxicity. Recently, mTOR inhibitors such as sirolimus and everolimus (EVR) have been used with or without CNIs in LT recipients for their renal-sparing effect. We conducted a systematic review and meta-analysis of randomized controlled trials (RCT) that examined the effect of EVR with CNI minimization or withdrawal on renal function in LT recipients. RCT of primary adult LT recipients with baseline GFR >30mL/min who received EVR with CNI minimization or withdrawal were included. Four RCTs (EVR n=465, control n=428) were included. In three RCTs, EVR was initiated 4weeks following LT; these studies were used to assess the primary outcome. All four studies were used to assess the secondary outcomes. Based on this study, EVR use with CNI minimization in LT recipients is associated with improved renal function at 12months by GFR of 10.2mL/min (95% CI: 2.75-17.8). EVR use was not associated with an increased risk of biopsy-proven acute rejection (RR 0.68, 95% CI: 0.31-1.46), graft loss (RR 1.60, 95% CI: 0.51-5.00), or mortality (RR 1.34, 95% CI 0.62-2.90). However, it was associated with an increased risk of overall infections (RR 1.45, 95% CI: 1.10-1.91).

Intra-individual variability of mycophenolic acid concentration according to renal function in liver transplant recipients receiving mycophenolate monotherapy.

Backgrounds/AimsMycophenolate mofetil (MMF) has wide inter- and intra-individual variability of mycophenolic acid (MPA) after liver transplantation (LT). On this study, we aimed to analyse the intra-individual variability of MPA concentration in stable adult LT recipients receiving MMF monotherapy and develop a method to determine the target level in the situation of wide intra-individual variability.MethodsThis retrospective cross-sectional study included 30 LT recipients. All patients received MMF monotherapy at a dose of 500 mg twice daily for ≥2 years and were divided into two groups based on renal function. MPA concentration-associated values were presented as mean with standard deviation and coefficient of variation (CV).ResultsThe normal renal function group (n=15) showed a mean 12-hour MPA concentration of 2.5±0.5 µg/ml (range, 1.8±0.5 to 3.6±0.7 µg/ml) and a mean CV of 20.4±7.7% (range, 8.7% to 39.4%). In the renal dysfunction group (n=15), the 12-hour MPA concentration fluctuated more widely with a mean value of 3.7±0.9 µg/ml (range, 2.8±0.8 to 5.1±1.2 µg/ml) and a mean CV of 24.5±4.9% (range, 17.1% to 37.5%). The 12-hour MPA concentration was significantly higher in the renal dysfunction group, as compared to the normal renal function group (p=0.001); whereas, the CV was not significantly different between the two groups (p=0.093).ConclusionsWe determined the inter- and intra-individual variability of 12-hour MPA concentration after LT. The results suggested that therapeutic drug monitoring of MPA is necessary due to the inter-individual and intra-individual variability of MMF pharmacokinetics, especially in LT recipients with renal dysfunction.

One-Year Follow-up of the Changes in Renal Function After Liver Transplantation in Patients Without Chronic Kidney Disease

BackgroundImpaired renal function is a strong risk factor for morbidity and mortality after liver transplantation (LT). There is clearly a progressive deterioration in renal function after LT. The greatest loss of renal function occurs within the 1st year after LT. Several factors, including calcineurin inhibitors, are associated with decreased renal function. The aims of the present study were to identify changes in renal function before and after LT and to determine the risk factors related to decreased renal function after LT. MethodsWe reviewed medical records of 106 LT recipients without moderate to severe chronic kidney disease (estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 m2). We investigated eGFR changes from before to 1 year after LT with the use of propensity score matching. Statistical significance of differences between clinical parameters and 1-year eGFR changes was assessed with the use of univariate and multivariate analyses. ResultsMean age was 49.5 ± 10.9 years, and 66% of the patients were male. Mean differences in 1-year eGFR and serum creatinine were −32.0 ± 29.2 mL/min/1.73 m2 and 0.3 ± 0.3 mg/dL, respectively. Variables significantly associated with renal dysfunction 1 year after LT were old age, low pre-LT eGFR, low post-LT hemoglobin, and perioperative acute kidney injury. Multivariate analysis showed that pre-LT renal function was an independent risk factor for decreased renal function after LT. However, there was no significant correlation between 1-year eGFR change and serum tacrolimus level. ConclusionsRenal function significantly decreased the 1st year after LT, and baseline renal function was an independent risk factor for worsening renal function in LT recipients.