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1.
Front Med (Lausanne) ; 11: 1325128, 2024.
Article in English | MEDLINE | ID: mdl-38660426

ABSTRACT

Introduction: Apolipoprotein-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. Methods: Genomic 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. Results: Our 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. Conclusion: Our 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.

2.
Clin Transplant ; 38(1): e15172, 2024 01.
Article in English | MEDLINE | ID: mdl-37897198

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 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). CONCLUSION: This analysis showed that XRT is safe and effective as de novo maintenance IS in a steroid-free protocol with RATG.


Subject(s)
Liver Transplantation , Tacrolimus , Humans , Graft Rejection/etiology , Graft Rejection/prevention & control , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/adverse effects , Liver Transplantation/adverse effects , Prospective Studies , Quality of Life , Steroids , Tacrolimus/administration & dosage , Tacrolimus/adverse effects , Delayed-Action Preparations
3.
bioRxiv ; 2023 Oct 19.
Article in English | MEDLINE | ID: mdl-37905084

ABSTRACT

Introduction: Apolipoprotein-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 haplotype-centric model. Methods: Genomic DNA was extracted from recipient PBMCs using SDS lysis buffer and proteinase K. Quantitative PCR assay with modified forward primers and a common reverse primer enabled us to identify single nucleotide polymorphisms (SNPs) and the 6-bp deletion quantitatively. Additionally, we used sanger sequencing to verify our QPCR findings. Results: Our novel probe-independent qPCR effectively distinguished homozygous wild-type, heterozygous SNPs/deletion, and homozygous SNPs/deletion, with at least 4-fold differences. High prevalence of APOL1 variants was observed (18% two-risk alleles, 34% one-risk allele) in our recipient cohort. Intriguingly, up to 12-month follow-up revealed no significant impact of recipient APOL1 variants on transplant outcomes. Ongoing research will encompass more time points and a larger patient cohort, allowing a comprehensive evaluation of G1/G2 variant subgroups categorized by new haplotype scores, enriching our understanding. Conclusions: Our 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.

4.
Transplant Direct ; 8(6): e1342, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35651584

ABSTRACT

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.

5.
Clin Transplant ; 35(5): e14281, 2021 05.
Article in English | MEDLINE | ID: mdl-33690929

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.


Subject(s)
Hepatitis C, Chronic , Hepatitis C , Liver Transplantation , Antiviral Agents/therapeutic use , Hepacivirus/genetics , Hepatitis C/drug therapy , Hepatitis C, Chronic/drug therapy , Humans , RNA, Viral , Treatment Outcome
6.
PLoS One ; 15(5): e0232006, 2020.
Article in English | MEDLINE | ID: mdl-32407331

ABSTRACT

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.


Subject(s)
Liver/diagnostic imaging , Magnetic Resonance Imaging , Non-alcoholic Fatty Liver Disease/pathology , Aged , Area Under Curve , Bilirubin/analysis , Biomarkers/metabolism , Female , Humans , International Normalized Ratio , Liver/pathology , Liver Transplantation , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/diagnostic imaging , Pilot Projects , ROC Curve , Transaminases/metabolism , Transplantation, Homologous
7.
Nephron ; 144(3): 126-137, 2020.
Article in English | MEDLINE | ID: mdl-32007998

ABSTRACT

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.


Subject(s)
Antilymphocyte Serum/pharmacology , Histocompatibility Antigens Class II/immunology , Isoantibodies/immunology , Kidney Transplantation/adverse effects , Liver Transplantation , Adult , Aged , Allografts , Female , Graft Rejection/etiology , Humans , Kidney Transplantation/mortality , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies , Tissue Donors
8.
Ren Fail ; 42(1): 40-47, 2020 Nov.
Article in English | MEDLINE | ID: mdl-31875761

ABSTRACT

Background: De novo Donor Specific Antibodies (DSA) are considered as a risk factor for the kidney allograft outcomes in recipients after simultaneous liver-kidney transplantation (SLKT). We hypothesized that length of hospital stay (LOS) might be associated with de novo DSA development of due to the increased likelihood of receiving blood transfusions with reduced immunosuppressive regimens.Methods: This study is a single-center, retrospective cohort study consisting of 85 recipients who underwent SLKT from 2009 to 2018 in our hospital. We divided the patients into two groups according to LOS [long hospital stay (L) group (LOS >14 days) and short hospital stay (S) group (LOS ≤14 days)]. Propensity score (PS) has been created using logistic regression to predict LOS greater than median of 14 days. The association between the presence of de novo DSA and LOS was assessed by logistic regression models adjusted for PS.Results: The mean age at transplantation of the entire cohort was 55.5 ± 10.1 years. Sixty percent of the recipients were male and Caucasian. Median LOS in (L) group was three-fold longer than (S) group [L: median 30 days (IQR: 21-52), S: median 8.5 days (IQR: 7-11)]. Eight patients developed de novo DSA after SLKT (9.4%), all of them were in (L) group. Longer LOS was significantly associated with higher risk of development of de novo DSA in unadjusted (OR+ each 5 days: 1.09, 95% CI:1.02-1.16) and PS adjusted (OR+ each 5 days: 1.11, 95% CI:1.02-1.21) analysis.Conclusion: Longer hospitalization is significantly associated with the development of de novo DSA in SLKT.


Subject(s)
Graft Rejection/epidemiology , Isoantibodies/blood , Kidney Transplantation/adverse effects , Length of Stay/statistics & numerical data , Liver Transplantation/adverse effects , Adult , Aged , Allografts/immunology , Blood Transfusion/statistics & numerical data , Female , Graft Rejection/blood , Graft Rejection/immunology , Graft Rejection/prevention & control , Humans , Immunosuppressive Agents/administration & dosage , Incidence , Isoantibodies/immunology , Isoantigens/immunology , Kidney/immunology , Liver/immunology , Male , Middle Aged , Retrospective Studies , Risk Factors , Time Factors
9.
Transpl Int ; 33(2): 202-215, 2020 02.
Article in English | MEDLINE | ID: mdl-31647143

ABSTRACT

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.


Subject(s)
Isoantibodies/immunology , Kidney Transplantation , Liver Transplantation , Transplant Recipients , Complement C1q/immunology , Female , Graft Rejection , Graft Survival , Humans , Kidney , Liver , Male , Middle Aged , Retrospective Studies , Tissue Donors
10.
J Surg Case Rep ; 2019(12): rjz356, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31867097

ABSTRACT

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.

11.
J Surg Case Rep ; 2019(12): rjz350, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31857891

ABSTRACT

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.

12.
Am J Transplant ; 19(11): 3046-3057, 2019 11.
Article in English | MEDLINE | ID: mdl-31306549

ABSTRACT

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.


Subject(s)
Graft Survival , Hepatitis C/transmission , Kidney Failure, Chronic/surgery , Kidney Transplantation/methods , Tissue Donors/supply & distribution , Transplant Recipients/statistics & numerical data , Adult , Antiviral Agents/therapeutic use , Female , Follow-Up Studies , Glomerular Filtration Rate , Hepacivirus/isolation & purification , Hepatitis C/drug therapy , Hepatitis C/virology , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Factors , Tissue and Organ Procurement/methods
13.
Ann Transplant ; 24: 70-74, 2019 Feb 07.
Article in English | MEDLINE | ID: mdl-30728343

ABSTRACT

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.


Subject(s)
Iliac Artery/pathology , Kidney Transplantation/methods , Pancreas Transplantation/methods , Vascular Calcification/pathology , Vascular Grafting/methods , Adult , Female , Humans , Male , Middle Aged , Treatment Outcome
14.
Transplant Direct ; 4(4): e356, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29707627

ABSTRACT

BACKGROUND: Despite substantial evidence demonstrating clear benefit, rates of preemptive kidney transplantation (PreKTx) remain low in the United States. Our goal was to identify barriers to PreKTx. METHODS: Using a telephone-administered questionnaire including questions about barriers, timing of referral, timing of education, we retrospectively studied first living donor kidney transplant recipients (2006-2010) at Mayo Clinic, Rochester, MN. Of 235 patients, 145 (62%) responded to the questionnaire (74 PreKTx and 71 non-PreKTx). We compared categorical data with Fisher exact test and median times with Wilcoxon rank sum test. RESULTS: Polycystic kidney disease (PCKD), longer median time between diagnosis and transplant, and time between education about transplant and transplant correlated with PreKTx (P < 0.01). The presence of at least 1 patient-identified barrier (lack of referral, financial barriers, medical barriers, no identified living donor and donor evaluation delays) was associated with non-PreKTx (0.034) though no single barrier predominated. Age, education level, insurance status and source of referral (primary care, nephrology, and nonphysician referral) were not associated with the rate of PreKTx. Univariate logistic regression identified white race, PCKD, and increased time from diagnosis as factors favoring PreKTx; PCKD and increased time remained significant factors after multivariate analysis. CONCLUSIONS: Even among a patient population that is primarily white, educated, and has a spouse or first-degree relative donor, PreKTx rates remain concerningly low. Increased time between diagnosis or education and transplant are predictors of PreKTx. Greater emphasis on transplant education earlier in the stages of chronic kidney disease and community outreach from transplant centers may help to increase the rate of PreKTx.

15.
Clin Transplant ; 32(5): e13246, 2018 05.
Article in English | MEDLINE | ID: mdl-29577449

ABSTRACT

BACKGROUND: Sorafenib has shown survival benefits in patients with advanced HCC; however, limited data are available on its role in OLT recipients with advanced HCC in the explant. AIM: Evaluate the role of preemptive sorafenib therapy on HCC recurrence and survival after OLT with advanced HCC on explant pathology. METHODS: We retrospectively reviewed the outcome after OLT of all HCC recipients with advanced HCC in the explant pathology from 04/2006 to 12/2012 based on preemptive treatment with sorafenib. RESULTS: During the observation period, 217 HCC recipients underwent OLT; 50 explants revealed advanced HCC. After exclusion of 5 patients who were lost to follow-up, 45 LT recipients were finally included for analysis. Recipients were grouped as sorafenib Gr (N = 25) and nonsorafenib Gr (N = 20). Both recurrence-free survival (RFS) (P = .67) and overall survival were similar between groups (P = .53) on Kaplan-Meier analysis. Additionally, sorafenib use was neither associated with HCC recurrence-free survival (HR 0.74, 95% CI [0.32-1.70]; P = .48) nor overall survival (HR 0.92, 95% CI [0.39-2.15], P = .84) on multivariate Cox proportional hazard model with sorafenib use as time-varying covariates. CONCLUSION: Preemptive treatment with sorafenib in OLT recipients with high-risk features in explant does not improve HCC recurrence-free or overall survival.


Subject(s)
Antineoplastic Agents/adverse effects , Carcinoma, Hepatocellular/mortality , Graft Rejection/mortality , Liver Neoplasms/mortality , Liver Transplantation/mortality , Neoplasm Recurrence, Local/mortality , Sorafenib/adverse effects , Aged , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/therapy , Female , Follow-Up Studies , Graft Rejection/etiology , Graft Survival , Humans , Liver Neoplasms/pathology , Liver Neoplasms/therapy , Liver Transplantation/adverse effects , Male , Middle Aged , Neoplasm Recurrence, Local/etiology , Neoplasm Recurrence, Local/therapy , Preoperative Care , Prognosis , Retrospective Studies , Risk Factors , Survival Rate
16.
Transplantation ; 101(4): 793-803, 2017 04.
Article in English | MEDLINE | ID: mdl-28099403

ABSTRACT

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.


Subject(s)
Coronary Artery Disease/surgery , Coronary Stenosis/surgery , End Stage Liver Disease/surgery , Liver Transplantation , Myocardial Revascularization , Adult , Coronary Angiography , Coronary Artery Disease/complications , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/mortality , Coronary Stenosis/complications , Coronary Stenosis/diagnostic imaging , Coronary Stenosis/mortality , End Stage Liver Disease/complications , End Stage Liver Disease/diagnosis , End Stage Liver Disease/mortality , Female , Humans , Kaplan-Meier Estimate , Liver Function Tests , Liver Transplantation/adverse effects , Liver Transplantation/mortality , Male , Medical Records , Middle Aged , Myocardial Revascularization/adverse effects , Myocardial Revascularization/mortality , Postoperative Complications/etiology , Proportional Hazards Models , Retrospective Studies , Risk Factors , Severity of Illness Index , Time Factors , Treatment Outcome
17.
Transplantation ; 101(4): 867-872, 2017 Apr.
Article in English | MEDLINE | ID: mdl-27495758

ABSTRACT

BACKGROUND: Given high dialysis mortality rates for patients older than 60 years, accepting a kidney with a high Kidney Donor Profile Index (KDPI) score could enable earlier and potentially preemptive transplantation (preKT). However, evidence regarding the risks of high KDPI allografts in older patients is limited. Our objective was to determine the relative benefit for older patients of KDPI greater than 85% transplant either preemptively or not compared with remaining on the waitlist. METHODS: United Network of Organ Sharing data from 2003 to 2012 for adult deceased donor kidney transplant candidates was analyzed to evaluate patient survival in patients older than 60 years for preKT and non-preKT KDPI greater than 85% transplants compared with candidates remaining on the waitlist including patients who received KDPI 0% to 85% transplants according to multivariate Cox regression models. RESULTS: In the first year posttransplant for KDPI greater than 85% of transplants in recipients older than 60 years, preKT had a reduced mortality hazard (hazards ratio [HR], 0.61; 95% confidence interval [95% CI], 0.41-0.90) and non-preKT an increased mortality hazard (HR, 1.15; 95% CI, 1.03-1.27) compared with the waitlist including KDPI 0% to 85% transplant recipients. At 1 to 2 years and after 2 years, both KDPI greater than 85% groups had significant reductions in mortality (1-2 years: preKT HR, 0.38; 95% CI, [0.23-0.60] and non-preKT HR, 0.52; 95% CI, 0.45-0.61; and 2+ years: preKT HR, 0.50; 95% CI, 0.38-0.66 and non-preKT HR, 0.64; 95% CI, 0.58-0.70, respectively). CONCLUSIONS: PreKT and non-preKT KDPI greater than 85% transplant was associated with lower mortality hazard after the first year compared with the waitlist including KDPI 0% to 85% transplants in patients older than 60 years. Further consideration should be given to increased utilization of high KDPI grafts in older patients with the goal of avoiding or limiting time on dialysis.


Subject(s)
Donor Selection , Kidney Failure, Chronic/surgery , Kidney Transplantation , Time-to-Treatment , Tissue Donors/supply & distribution , Waiting Lists , Age Factors , Aged , Chi-Square Distribution , Female , Graft Survival , Humans , Kaplan-Meier Estimate , Kidney Failure, Chronic/diagnosis , Kidney Failure, Chronic/mortality , Kidney Transplantation/adverse effects , Kidney Transplantation/mortality , Male , Middle Aged , Multivariate Analysis , Postoperative Complications/etiology , Proportional Hazards Models , Registries , Renal Dialysis , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , United States , Waiting Lists/mortality
18.
Am J Surg ; 211(6): 1064-70, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26746567

ABSTRACT

BACKGROUND: Hepatitis C virus (HCV) infection is thought to be associated with immune dysfunction. We hypothesized that HCV status would be associated with increased infectious complications in the surgical intensive care unit (SICU). METHODS: All patients admitted to our SICU between 2008 and 2012 were included. We evaluated 90-day mortality and infectious complications in the SICU. Multivariate logistic regression was performed to identify predictors of infectious complications and 90-day mortality. RESULTS: A total of 1,941 patients were included. The HCV-positive group had a higher overall incidence of infectious complications (25% vs 18%), particularly ventilator-associated pneumonia (VAP) and bacteremia. The increased incidences of VAP and bacteremia persisted when cirrhotic patients were excluded. Prolonged intubation (Odds Ratio [OR] = 2.1), abdominal surgery (OR = 1.6), and model for end-stage liver disease ≥ 15 (OR = 1.4) were independent predictors of SICU infectious complications. CONCLUSIONS: The HCV-positive group had an increased incidence of infectious complications in the SICU, particularly VAP and bacteremia. This effect persisted when cirrhotic patients were excluded.


Subject(s)
Cross Infection/epidemiology , Hepatitis C, Chronic/complications , Hospital Mortality , Intensive Care Units , Postoperative Complications/immunology , Adult , Aged , Bacteremia/diagnosis , Bacteremia/epidemiology , Bacteremia/immunology , Cause of Death , Critical Care , Cross Infection/physiopathology , Databases, Factual , Female , Follow-Up Studies , Hepatitis C, Chronic/diagnosis , Hepatitis C, Chronic/immunology , Humans , Immunocompromised Host , Logistic Models , Male , Middle Aged , Multivariate Analysis , Postoperative Complications/diagnosis , Postoperative Complications/epidemiology , Retrospective Studies , Risk Assessment , Survival Rate , United States
20.
Transplantation ; 100(5): 1120-7, 2016 05.
Article in English | MEDLINE | ID: mdl-26479285

ABSTRACT

BACKGROUND: Preemptive kidney transplantation (preKT) is associated with higher patient survival, improved quality of life, and lower costs. However, only a minority of patients receives preKT. The aim of this study was to examine changes over the past decade in rates of preKT, focusing on living donor kidney transplantation (LDKT) and specifically recipients who underwent kidney transplantation within 1 year of initiating dialysis. METHODS: Using United Network of Organ Sharing data, we examined retrospectively all kidney transplant candidates (n = 369 103) and recipients (n = 141 254) from 2003 to 2012 in the United States focusing on LDKT (n = 47 108). Predictors of preKT were examined, and patient and graft survival were compared for preKT, pretransplant dialysis less than 1 year, and pretransplant dialysis recipients of 1 year or longer. RESULTS: PreKT occurred in only 17% of recipients overall and 31% of LDKT recipients. Medicare patients (odds ratio [OR], 0.29; 95% confidence interval [95% CI], 0.28-0.31), diabetics (OR, 0.75; 95% CI, 0.69-0.80), and minorities (Hispanics OR, 0.62; 95% CI, 0.57-0.68 and African Americans OR, 0.58; 95% CI, 0.53-0.63) were less likely to receive preKT. Dialysis recipients for less than 1 year comprised 30% of nonpreemptive LDKT. Dialysis recipients of less than 1 year had similar patient survival to preKT (5 years: preKT, 94%; dialysis < 1 year, 94%; dialysis ≥ 1 year, 89%; P < 0.01), but decreased death-censored graft survival (5 years: preKT, 93%; dialysis < 1 year, 89%; and dialysis ≥ 1 year, 89%; P < 0.01). CONCLUSIONS: PreKT remains an unrealized goal for the majority of recipients. Medicare patients, diabetics, and minorities are less likely to receive preKT. Almost one third of nonpreemptive LDKT recipients were dialyzed for less than 1 year, highlighting an important target for improvement.


Subject(s)
Kidney Failure, Chronic/epidemiology , Kidney Failure, Chronic/surgery , Kidney Transplantation/methods , Adult , Aged , Diabetes Complications , Female , Graft Survival , Humans , Kidney Failure, Chronic/ethnology , Living Donors , Male , Medicare , Middle Aged , Minority Groups , Proportional Hazards Models , Quality of Life , Renal Dialysis , Retrospective Studies , Tissue and Organ Procurement , Treatment Outcome , United States , Young Adult
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