IntroductionApolipoprotein-L1 (APOL1) is a primate-specific protein component of high-density lipoprotein (HDL). Two variants of APOL1 (G1 and G2), provide resistance to parasitic infections in African Americans but are also implicated in kidney-related diseases and transplant outcomes in recipients. This study aims to identify these risk variants using a novel probe-independent quantitative real-time PCR method in a high African American recipient cohort. Additionally, it aims to develop a new stratification approach based on a haplotype-centric model.MethodsGenomic DNA was extracted from recipient PBMCs using SDS lysis buffer and proteinase K. A quantitative PCR assay with modified forward primers and a common reverse primer enabled us to quantitatively identify single nucleotide polymorphisms (SNPs) and the 6-bp deletion. Additionally, we used Sanger sequencing to verify our QPCR findings.ResultsOur novel probe-independent qPCR effectively distinguished homozygous wild-type, heterozygous SNPs/deletions, and homozygous SNPs/deletions, with at least 4-fold differences. A high prevalence of APOL1 variants was observed (18% two-risk alleles, 34% one-risk allele) in our recipient cohort. Intriguingly, no significant impact of recipient APOL1 variants on transplant outcomes was observed up to 12-month of follow-ups. Ongoing research will encompass more time points and a larger patient cohort, allowing for a comprehensive evaluation of G1/G2 variant subgroups categorized by new haplotype scores, enriching our understanding.ConclusionOur cost-effective and rapid qPCR technique facilitates APOL1 genotyping within hours. Prospective and retrospective studies will enable comparisons with long-term allograft rejection, potentially predicting early/late-stage transplant outcomes based on haplotype evaluation in this diverse group of kidney transplant recipients.

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

PURPOSEOur 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).METHODSAll 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.RESULTSWe 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 m2 . 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).CONCLUSIONThis analysis showed that XRT is safe and effective as de novo maintenance IS in a steroid-free protocol with RATG.

Background. Long-term liver outcome in hepatitis C virus (HCV)-negative kidney recipients who acquired HCV infection from viremic donors is of intense interest in the transplant community. We evaluated the incidence of fibrosis in liver biopsy specimens of recipients who were transplanted with HCV-infected grafts. Methods. Patients were evaluated in the hepatology clinic, and 29 patients agreed to undergo liver biopsy. The liver histology was scored by the meta-analysis of histological data in viral hepatitis scoring system and was assessed by hepatopathologists. The fibrosis score was compared between patients who initiated direct-acting antiviral (DAA) within 6 wk (n = 6) and after 6 wk (n = 29). Results. Eighty-nine aviremic patients were transplanted with HCV-infected grafts between March 2018 and October 2019. All patients developed HCV infection and were treated with DAA treatment after kidney transplantation (median, 70 d; interquartile range, 55–85 d). All patients (n = 89) achieved sustained virologic response with DAA. The median follow-up time from kidney transplant to liver biopsy was 28 mo (interquartile range, 26–30 mo). Twenty-five patients (86%) had F0, and 4 patients (14%) had F1 fibrosis. No patient had advanced fibrosis (F3–F4). Grade 1 inflammation was present in 6 (21%) patients, whereas 26 (90%) patients had iron accumulation in the hepatocytes and reticuloendothelial cells. There was no difference in the fibrosis score between patients who received treatment within 6 wk versus after 6 wk (P = 0.55). Conclusions. Kidney transplantation of HCV-infected graft to HCV-negative recipients is safe and has no long-term liver-related complications with successful eradication of HCV. In our cohort, delayed treatment did not affect sustained virologic response or liver histology.

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.

Introduction and Objective: 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. Methods: 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. Results: 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. Conclusions: 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.

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.

Our aim was to evaluate the safety of transplanting kidneys from HCV-infected donors in HCV-uninfected recipients. Data collected from 53 recipients in a single center, observational study included donor and recipient characteristics, liver and kidney graft function, new infections and de novo donor-specific antibodies and renal histology. Treatment with a direct-acting antiviral regimen was initiated when HCV RNA was detected. The mean ± SD age of recipients was 53 ± 11 years, 34% were female, 19% and 79% of recipients were white and African American, respectively. The median and interquartile range (IQR) time between transplant and treatment initiation was 76 (IQR: 68-88) days. All 53 recipients became viremic (genotype: 1a [N = 34], 1b [N = 1], 2 [N = 3], and 3 [N = 15]). The majority (81%) of recipients did not experience clinically significant increases (>3 times higher than upper limit of the normal value) in aminotransferase levels and their HCV RNA levels were in the 5 to 6 log range. One patient developed fibrosing cholestatic hepatitis with complete resolution. All recipients completed antiviral treatment and 100% were HCV RNA-negative and achieved 12-week sustained virologic response. The estimated GFRs at end of treatment and 12-week posttreatment were 67 ± 21 mL/min/1.73 m2 and 67 ± 17 mL/min/1.73 m2 , respectively. Four recipients developed acute rejection. Kidney transplantation from HCV-infected donors to HCV-negative recipients should be considered in all eligible patients.

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.

Iliac artery calcification is a common phenomenon complicating renal transplantation, particularly in those with diabetes. The potential for vascular clamp injury can threaten the renal allograft, ipsilateral lower extremity, or both. Utilization of internal balloon occlusion can allow for placement of a “Chimney Patch” graft, fashioned from a deceased donor artery, to the calcified vessel, eliminating the risk of clamp injury and minimizing warm ischemic time. We present a series of 6 patients transplanted with internal balloon occlusion with successful renal and pancreatic allograft function and no ipsilateral vascular complications. Internal balloon occlusion is a safe and effective adjunct for renal or pancreas transplant to prevent clamp injury with no adverse effect on allograft function.

Cytomegalovirus (CMV) is a common posttransplant infection, most commonly seen in settings of excessive immunosuppression. Before the advent of CMV specific antiviral therapies, the standard treatment approaches for CMV disease were immunosuppression reductions to let the transplant recipient mount an immunologic response against CMV. Additionally, CMV is rarely identified as causing stricturing enteritis and has not previously been reported as causing stricturing enteritis in an adult transplant recipient. All identified reports of stricturing CMV enteritis have been reported in either pediatric patient populations or those with severe immunosuppression from human immunodeficiency virus and acquired immune deficiency syndrome. Our report presents the unusual case of an adult liver transplant recipient many years after transplant and on minimal immunosuppression with mycophenolate alone who developed stricturing CMV enteritis.

Hemobilia, or hemorrhage into the biliary system, is an unusual cause of gastrointestinal bleeding most commonly seen in accidental or iatrogenic trauma. We present the rare case of a 43-year-old gentleman who presents with an intrahepatic pseudoaneurysm caused by cholecystitis. The management of the hemobilia was technically challenging requiring multiple interventional procedures. We review the pathophysiology and treatment strategies for this rare case of gastrointestinal hemorrhage.