Abstract Purpose Our study hypothesis was that once daily dosing of extended‐release tacrolimus (XRT) would be a safe and effective immunosuppression (IS) with the potential to decrease adverse events (AEs) associated with immediate release tacrolimus (IRT) after liver transplantation (LT). Methods All patients receiving LT at our center received rabbit anti‐thymocyte globulin (RATG) induction therapy. Eligible patients were randomized in a 1:1 fashion to receive either XRT or IRT. Antimicrobial prophylaxis was the same between arms, and both groups received an antimetabolite for the first 6 months following LT. Patients were then followed at pre‐determined study intervals for the following year after LT. We administered the RAND‐36SF survey to assess patient's health‐related quality of life at pre‐determined intervals. All analysis was performed with an intention to treat basis. Results We screened 194 consecutive patients and enrolled 110. Our control and study arms were well matched. Transplant characteristics were similar between groups. At all timepoints, both arms had similar serum creatinine and estimated glomerular filtration rate (eGFR), calculated by MDRD6 equation, with post‐transplant GFRs between 60 and 70 mL/min/1.73 m 2 . Tacrolimus trough levels were similar between arms. The XRT arm had fewer AEs (166) and fewer serious AEs (70) compared to IRT (201 and 99, respectively). AEs most commonly were renal, infectious, or gastrointestinal in nature. While not statistically significant, XRT was held temporarily (25 vs. 35 cases) or discontinued (3 vs. 11 cases) less frequently than IRT and had fewer instances of rejection (7 vs. 12 cases). Conclusion This analysis showed that XRT is safe and effective as de novo maintenance IS in a steroid‐free protocol with RATG.
As quality measures increasingly become tied to payment, evaluating the most effective ways to provide high-quality care becomes more important.
Objectives
To determine whether mandated reporting for ventilator and catheter bundle compliance is correlated with decreased infection rates, and to determine whether labor-intensive audits are correlated with compliance.
Design, Setting, and Participants
Multiyear retrospective review of aggregated data from all patients admitted to 15 intensive care units in a Veterans Affairs hospital setting (the Veterans Integrated Service Network 16) from 2009 to 2011.
Exposures
Ventilator-associated pneumonia and catheter-related bloodstream infections.
Main Outcomes and Measures
Mean rates of ventilator-associated pneumonia and catheter-related bloodstream infection were analyzed by year. Relationships between infection rates, self-reported compliance, and audits were analyzed by Pearson correlation.
Results
During the study period, ventilator-associated pneumonia decreased from 2.50 to 1.60 infections per 1000 ventilator days (P = .07). The rate of pneumonia was not correlated with self-reported compliance overall (R = 0.19) or by individual year (2009,R = 0.30; 2010,R = 0.24; 2011,R = 0.46); there was a correlation in cardiac intensive care units (R = −0.70) but not other types of intensive care units (mixed,R = −0.18; medical,R = 0.42; surgical,R = 0.34). Catheter-related bloodstream infections decreased from 2.38 to 0.73 infections per 1000 catheter days (P = .04). The rate of catheter infection was not correlated with self-reported compliance overall (R = −0.18), by individual year (2009,R = −0.39; 2010,R = −0.42; 2011,R = 0.37), or by intensive care unit type (mixed,R = −0.19; cardiac,R = 0.55; medical,R = 0.17; surgical,R = −0.44).
Conclusions and Relevance
Current mandated self-reported compliance and audit measures are poorly correlated with decreased ventilator-associated pneumonia or catheter-related bloodstream infection.
Background The utility of ex vivo Magnetic resonance imaging proton density fat fraction (MRI-PDFF) in donor liver fat quantification is unknown. Purpose To evaluate the diagnostic accuracy and utility in predicting early allograft dysfunction (EAD) of ex vivo MRI-PDFF measurement of fat in deceased donor livers using histology as the gold standard. Methods We performed Ex vivo, 1.5 Tesla MRI-PDFF on 33 human deceased donor livers before implantation, enroute to the operating room. After the exclusion of 4 images (technical errors), 29 MRI images were evaluable. Histology was evaluable in 27 of 29 patients. EAD was defined as a peak value of aminotransferase >2000 IU/mL during the first week or an INR of ≥1.6 or bilirubin ≥10 mg/dL at day 7. Results MRI-PDFF values showed a strong positive correlation (Pearson’s correlation coefficient) when histology (macro-steatosis) was included (r = 0.78, 95% confidence interval 0.57‐0.89, p<0.0001). The correlation appeared much stronger when macro plus micro-steatosis were included (r = 0.87, 95% confidence interval 0.72‐0.94, p<0.0001). EAD was noted in 7(25%) subjects. AUC (Area Under the Curve) for macro steatosis (histology) predicted EAD in 73% (95% CI: 48–99), micro plus macro steatosis in 76% (95% CI: 49–100). AUC for PDFF values predicted EAD in 67(35–98). Comparison of the ROC curves in a multivariate model revealed, adding MRI PDFF values to macro steatosis increased the ability of the model in predicting EAD (AUC: 79%, 95% CI: 59–99), and addition of macro plus micro steatosis based on histology predicted EAD even better (AUC: 90%: 79–100, P = 0.054). Conclusion In this pilot study, MRI-PDFF imaging showed potential utility in quantifying hepatic steatosis ex-vivo donor liver evaluation and the ability to predict EAD related to severe allograft steatosis in the recipient.
<b><i>Introduction and Objective:</i></b> The impact of pretransplant donor-specific antibodies (DSAs), especially class II DSAs, on kidney allograft outcomes remains unclear in simultaneous liver-kidney transplantation (SLKT) recipients. <b><i>Methods:</i></b> We examined 85 recipients who consecutively underwent SLKT between 2009 and 2018 in our center. Associations between pretransplant DSA and worsening kidney function (WKF), kidney allograft loss, composite kidney outcome (WKF and/or antibody-mediated rejection and/or death-censored kidney allograft loss), death with functioning graft, and overall mortality were examined in survival analysis. WKF was defined as an eGFR decrease of 30% or greater from baseline, or 2 or more episodes of proteinuria, at least 90 days apart from each other. <b><i>Results:</i></b> The mean age at SLKT was 56 ± 10 years, and 62% of the recipients were male. More than one quarter (26%) of our recipients were African American. The 2 major causes of end-stage liver disease were hepatitis C (28%) and alcoholic hepatitis (26%). Nineteen recipients (22%) had pretransplant DSAs at the time of SLKT. The DSA(+) group and DSA(−) group had similar risk of WKF (unadjusted model: hazard ratio [HR] = 0.77, 95% confidence interval [CI]: 0.29–2.05 and adjusted model: HR = 0.36, 95% CI: 0.12–1.08); similar risk of composite kidney outcome (unadjusted model: HR = 1.04, 95% CI: 0.45–2.43 and adjusted model: HR = 0.53, 95% CI: 0.20–1.39); and similar risk of overall death (unadjusted model: HR = 1.23, 95% CI: 0.45–3.36 and adjusted model: HR = 1.28, 95% CI: 0.42–3.87). We found similar results when comparing different DSA subclasses (class I and II DSAs) with recipients without DSAs. <b><i>Conclusions:</i></b> The presence of pretransplant DSAs was not associated with worse kidney allograft outcomes from our single-center experience. Further prospective larger studies are strongly warranted.
Introduction: Liver transplant (LT) for alcoholic liver disease (ALD) requires careful evaluation of the patients at risk for recidivism. We sought to evaluate the accuracy of the Social Determinant Acuity Tool (S-DAT) to identify patients with low risk for alcohol relapse within 1 year post-LT. Methods: One Hundred forty patients who underwent LT for ALD in our institution from January 2016 to November 2021 were included in the study. All patients underwent a thorough psychosocial evaluation to obtain detailed pre-transplant alcohol use history and psychosocial variables. Post-LT alcohol relapse was defined as any alcohol use regardless of the amount or frequency. It was determined based on patient interviews or blood/urine tests (alcohol level, ethyl glucuronide, and/or phosphatidylethanol test). The Social Determinant Acuity Tool (S-DAT) was used to stratify patients from excellent (Score: 0-6) to poor candidates (score: 35-40) for post-LT outcomes. Results: The alcohol relapse rate at 1-year post-LT was 26 (18.6%), and the overall relapse rate was 33 (23.6%). Multivariate logistic regression analysis revealed S-DAT score (Odds Ratio [OR], 1.65; P=0.000), alcohol treatment post-LT (OR, 7.11; P=0.02), smoking history (OR, 0.15; P= 0.03) and marital status (OR, 60.28, P=0.000) were independent risk factors associated with post-LT alcohol relapse within 1 year (Table 1). The areas under the receiver operative curves (AUROC) of the S-DAT score to predict alcohol relapse within 1 year Post LT was 0.77 (Figure 1). For specific cut-off value, the S-DAT score (≥12), for predicting relapse risk, has 96.2%% sensitivity, 40.4% specificity, 26.9% positive predictive value, and 97.9% negative predictive value. Conclusion: The S-DAT score's high sensitivity and negative predictive values make it a good screening tool for identifying patients at low risk of alcohol relapse post-LT.Figure 1.: Accuracy of S-DAT Score in Predicting Alcohol Relapse within 1-Year Post LT. Table 1. - Multivariate Logistic Regression Analysis of Risk Factors for Alcohol Relapse within 1-Year Post LT Odds Ratio Std. Err 95% CI P Value Gender 1.03 0.79 0.23 - 4.60 0.97 Age at LT 0.98 0.035 0.91- 1.049 0.54 BMI at LT 0.96 0.06 0.86 -1.077 0.50 Working for Income at LT 1.68 1.36 0.34 - 8.25 0.52 S-DAT Score before LT 1.65 0.23 1.26 - 2.16 0.000 Alcohol Treatment Pre-LT 1.46 1.04 0.36 - 5.89 0.59 Alcohol Treatment Post-LT 7.11 6.32 1.24 - 40.58 0.02 AbsteinencePreLT6M 0.89 0.64 0.22 - 3.64 0.87 Psychiatric History Depression 0.31 0.46 0.02 - 5.692 0.43 Anxiety 1.34 2.02 0.07 - 25.69 0.85 Bipolar Disorder 11.21 17.13 0.56 - 223.90 0.11 Smoking History 0.16 0.13 0.03 - 0.84 0.03 Marital Status 60.28 68.44 6.51 - 557.89 0.000
There is a dearth of published data regarding the presence of post-transplant donor-specific antibodies (DSA), especially C1q-binding DSA (C1q+DSA), and patient and kidney allograft outcomes in simultaneous liver–kidney transplant (SLKT) recipients. We conducted a retrospective cohort study consisted of 85 consecutive SLKT patients between 2009 and 2018 in our center. Associations between presence of post-transplant DSA, including persistent and/or newly developed DSA and C1q+DSA, and all-cause mortality and the composite outcome of mortality, allograft kidney loss, and antibody-mediated rejection were examined using unadjusted and age and sex-adjusted Cox proportional hazards and time-dependent regression models. The mean age at SLKT was 56 years and 60% of the patients were male. Twelve patients (14%) had post-transplant DSA and seven patients (8%) had C1q+DSA. The presence of post-transplant DSA was significantly associated with increased risk of mortality (unadjusted model: Hazard Ratio (HR) = 2.72, 95% confidence interval (CI): 1.06–6.98 and adjusted model: HR = 3.20, 95% CI: 1.11–9.22) and the composite outcome (unadjusted model: HR = 3.18, 95% CI: 1.31–7.68 and adjusted model: HR = 3.93, 95% CI: 1.39–11.10). There was also higher risk for outcomes in recipients with C1q+DSA compared the ones without C1q+DSA. Post-transplant DSA is significantly associated with worse patient and kidney allograft outcomes in SLKT. Further prospective and large cohort studies are warranted to better assess these associations.
Coronary artery disease (CAD) is a significant problem during evaluation for liver transplantation (LT). We aim to assess survival in LT recipients based on presence, severity, extent of CAD, and cardiac events within 90 days of LT.Eighty-seven LT recipients with history of pre-LT angiogram (December 2005 to December 2012) were compared with 2 control groups without prior angiogram, 72 LT recipients matched for cardiovascular risk factors (control group I), and 119 consecutive LT recipients without any CV risk factors (control group II). CAD was assessed by (1) vessel score (≥50% reduction in luminal diameter), and (2) Extent score (Reardon scoring system).Of the 87 LT recipients (study group), 58 (66.7%) had none or less than 50% stenosis, 29 (33.3%) had obstructive CAD (≥50% stenosis), 7 (8%) with single-vessel disease, and 22 (25.3%) with multivessel disease. In the study group, irrespective of prerevascularization severity of CAD (P = 0.357), number of segments involved (0, 1-2, > 2 segments, P = 0.304) and extent of CAD based on Reardon score (0, 1-9, >10, P = 0.224), comparable posttransplant survival was noted. Overall, patient survival in the revascularized CAD group was comparable to angiogram group without obstructive CAD, and both control group I and control group II (P = 0.184, Log Rank). Postoperative cardiac events within 90 days of LT predicted poor survival in study group as well as control groups.Severity or extent of CAD does not impact post-LT survival, if appropriately revascularized. Early postoperative cardiac events are associated with inferior survival in LT recipients, irrespective of underlying CAD.
Abstract Background The virologic and histologic outcomes of a hepatitis C virus (HCV)–infected liver graft into an HCV‐negative recipient are not well understood. We aimed to evaluate the sustained virologic response (SVR) rate and the liver histology at 1 year post‐Orthotopic liver transplantation (OLT) with an HCV‐infected graft. Methods A total of 33 patients received the HCV antibody (Ab)+/nucleic acid amplification test (NAT)+ graft. Of these patients, 23 were HCV‐negative recipients and 10 were HCV‐positive recipients. The 1‐year biopsy data were available for 24 patients: 15 patients in HCV‐negative group who received an HCV Ab+/NAT+graft and 9 patients in HCV‐positive group who received an HCV Ab+/NAT+ graft. Patients with (+) HCV ribonucleic acid (RNA) were started on direct‐acting antiviral (DAA) treatment approximately 107 days after OLT using either a Glecaprevir‐Pibrentasvir or Sofosbuvir‐Velpatasvir or Sofosbuvir‐Ledipasvir. Results All patients ( n = 33) were treated with DAA and achieved SVR. The 1‐year post‐OLT liver biopsies were available in 24 patients: 9 patients had F1 and F2 fibrosis and 17 patients had minimal to moderate inflammation. There was no statistical difference in fibrosis and inflammation between the HCV‐negative vs. HCV‐positive recipients. All patients who received the NAT+ graft developed viremia and subsequently achieved SVR with treatment. Conclusion At 1 year protocol liver biopsy, patients had inflammation consistent with viral hepatitis despite the successful eradication of HCV.
