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1.
JCI Insight ; 8(6)2023 03 22.
Article in English | MEDLINE | ID: mdl-36749632

ABSTRACT

We assessed vaccine-induced antibody responses to the SARS-CoV-2 ancestral virus and Omicron variant before and after booster immunization in 57 patients with B cell malignancies. Over one-third of vaccinated patients at the pre-booster time point were seronegative, and these patients were predominantly on active cancer therapies such as anti-CD20 monoclonal antibody. While booster immunization was able to induce detectable antibodies in a small fraction of seronegative patients, the overall booster benefit was disproportionately evident in patients already seropositive and not receiving active therapy. While ancestral virus- and Omicron variant-reactive antibody levels among individual patients were largely concordant, neutralizing antibodies against Omicron tended to be reduced. Interestingly, in all patients, including those unable to generate detectable antibodies against SARS-CoV-2 spike, we observed comparable levels of EBV- and influenza-reactive antibodies, demonstrating that B cell-targeting therapies primarily impair de novo but not preexisting antibody levels. These findings support rationale for vaccination before cancer treatment.


Subject(s)
COVID-19 , Neoplasms , Humans , COVID-19 Vaccines , Antibody Formation , SARS-CoV-2 , Neoplasms/therapy , Antibodies, Monoclonal , Antibodies, Viral
2.
Cancers (Basel) ; 13(19)2021 Sep 23.
Article in English | MEDLINE | ID: mdl-34638251

ABSTRACT

The biomarkers α-fetoprotein (AFP), Lens culinaris agglutinin-reactive AFP fraction (AFP-L3), and des-γ-carboxy prothrombin (DCP) have emerging implications in hepatocellular carcinoma (HCC) surveillance, overall prognosis, and post-surgical recurrence risk. This retrospective study investigated treatment and bridge to liver transplant (LT) prognosis associated with AFP, AFP-L3%, and DCP biomarker profiles prior to liver-directed therapy (LDT). In a 140-patient cohort, each biomarker was associated with HCC progression risk using the established thresholds of AFP > 20 ng/mL, AFP-L3 > 15%, and DCP > 7.5 ng/mL. Over 60% of the cohort expressed at least one biomarker at baseline. Although most biomarker-positive patients expressed the clinical standard AFP (57/87), only 32% were positive for AFP alone. Biomarker accumulation increased HCC progression risk but was not associated with demographic factors or preserved liver function. Biomarker triple negative patients had smaller index HCC (p = 0.003), decreased multifocal burden (p = 0.010), and a higher objective response rate (ORR, 62% compared to 46%, p = 0.011). Expressing all three biomarkers at baseline was associated with dismal first-line ORR (12%) with a median time to progression (TTP) of only 181 days post-LDT. Patients with triple negative status for the HCC biomarkers AFP, AFP-L3%, and DCP have the highest first-line ORR with < 5% HCC progression 1-year post-LDT. Biomarker profiling can establish baseline prognosis for identifying optimal bridge to LT and downstaging to LT candidates with triple negative biomarker status and providing an ideal post-LDT target as a compliment to radiographic response.

3.
Liver Transpl ; 27(4): 548-557, 2021 04.
Article in English | MEDLINE | ID: mdl-33098277

ABSTRACT

Liver transplantation (LT) using allografts from hepatitis C virus (HCV)-viremic/nucleic acid testing-positive donors' (DNAT+) organs into HCV-aviremic recipients (rHCV-) has been limited owing to nearly universal HCV transmission and concerns regarding availability, safety, and efficacy post-LT with direct-acting antiviral (DAA) therapy. We report our experience of LT using DNAT+ organs into rHCV- as a routine standard of care. Following verification of DAA access, absence of critical drug-drug interactions (DDIs) with DAAs, and informed consent, allocated DNAT+ organs were offered to patients on the waiting list for LT irrespective of recipient HCV status. Between June 2018 and December 2019, 292/339 rHCV- received an LT. Forty-seven patients were excluded from analysis because of recipient HCV viremia, refusal to receive DNAT+ organs, or inability to receive DAA therapy post-LT. Of these 292 patients, 61 rHCV- received DNAT+ livers (study group), and 231 rHCV- received DNAT- (aviremic donors [nuclear acid test-negative donors]) livers (control group). Recipient and donor characteristics as well as 1-year post-LT patient and graft survival were similar between groups. In the study group, 4 patients died, and 1 patient required retransplantation within the first year post-LT (all unrelated to HCV); 56 patients received DAA therapy, with a median time from LT to the start of DAA treatment of 66.9 days (interquartile range [IQR], 36-68.5), and 51 patients completed DAA treatment, all achieving sustained virologic response for 12 or more weeks (SVR-12) (1 patient required retreatment owing to relapse following initial DAA therapy). No patients had evidence of fibrosing cholestatic hepatitis or extrahepatic manifestations of HCV. This report indicates that transplantation of DNAT+ livers into rHCV- and subsequent DAA therapy is associated with clinical outcomes comparable to those achieved with DNAT- allografts.


Subject(s)
Hepatitis C, Chronic , Hepatitis C , Liver Transplantation , Antiviral Agents/therapeutic use , Hepacivirus , Hepatitis C/drug therapy , Hepatitis C, Chronic/drug therapy , Humans , Liver Transplantation/adverse effects , Standard of Care , Tissue Donors , Viremia/drug therapy
4.
Clin Transplant ; 31(11)2017 Nov.
Article in English | MEDLINE | ID: mdl-28856732

ABSTRACT

INTRODUCTION: Early allograft dysfunction (EAD) is a well-defined clinical syndrome that reflects overall graft function within the first week after transplant. The aim of this study was to further refine the definition for EAD. METHOD: In this study, 1124 patients were included for analysis. Logistic regression was performed to identify markers of liver injury associated with 6-month patient and graft failure. RESULTS: Recursive partitioning identified cut-points for ALT/AST > 3000/6000 IU/dL observed within first week, with bilirubin ≥ 10 mg/dL and INR ≥ 1.6 on postoperative day 7 for the revised EAD model. The incidence of updated EAD was 15% (164/1124). Multivariable analysis identified eight risk factors associated with EAD: % macrosteatosis, donor location, donor weight, nonheart beating donors, type of organ transplanted, recipient-associated hepatocellular carcinoma, severity of postreperfusion syndrome, and the amount of transfused fresh frozen plasma. In the presence of EAD, the incidence of post-transplant renal replacement therapy and dialysis dependence increases. There was a significant association of the presence of EAD with 6-month mortality (12% vs 3%) and 6-month graft failure (8% vs 1%). CONCLUSION: Higher AST/ALT level needed as cutoff in comparison with the old EAD definition.


Subject(s)
Biomarkers/analysis , Liver Transplantation/adverse effects , Postoperative Complications , Primary Graft Dysfunction/diagnosis , Severity of Illness Index , Tissue Donors , Adolescent , Adult , Aged , Aged, 80 and over , Allografts , Child , Child, Preschool , Female , Follow-Up Studies , Graft Survival , Humans , Male , Middle Aged , Predictive Value of Tests , Primary Graft Dysfunction/etiology , Risk Factors , Time Factors , Young Adult
5.
Ochsner J ; 17(1): 25-30, 2017.
Article in English | MEDLINE | ID: mdl-28331444

ABSTRACT

BACKGROUND: Incidence of delirium after liver transplantation (LT) has been reported to occur in 10%-47% of patients and is associated with increased hospital and intensive care unit lengths of stay and poor outcomes. METHODS: Our primary objective was to evaluate the incidence and predisposing risk factors for developing delirium after LT. Our secondary objectives were to describe how delirium is managed in patients after LT, to examine the utilization of resources associated with delirium after LT, and to analyze the outcomes of patients who were treated for delirium after LT. RESULTS: In a population of 181 consecutive patients who received an LT, 38 (21.0%) developed delirium. In the multivariate analysis, delirium was associated with pretransplant use of antidepressants (odds ratio [OR] 3.34, 95% confidence interval [CI] 1.29-8.70) and pretransplant hospital admission for encephalopathy (OR 4.39, 95% CI 1.77-10.9). Patients with delirium spent more time on mechanical ventilation (2.0 vs 1.3 days, P=0.008) and had longer intensive care unit stays (4.6 vs 2.7 days, P=0.008), longer hospital stays (27.6 vs 11.2 days, P=0.003), and higher 6-month mortality (13.2% vs 1.4%, P=0.003) than patients who did not develop delirium. CONCLUSION: The presence of delirium is common after LT and is associated with high morbidity and mortality within the first 6 months posttransplant. Pretransplant factors independently associated with developing delirium after LT include prior use of antidepressants and pretransplant hospital admission for encephalopathy. Efforts should be made to identify patients at risk for delirium, as protocol-based management may improve outcomes in a cost-effective manner.

6.
Ochsner J ; 17(1): 42-45, 2017.
Article in English | MEDLINE | ID: mdl-28331447

ABSTRACT

BACKGROUND: Biliary complications remain a significant problem following liver transplantation. Several surgical options can be used to deal with a significant size mismatch between the donor and recipient bile ducts during the biliary anastomosis. We compared biliary transposition to recipient biliary ductoplasty in cadaveric liver transplant. METHODS: A total of 33 reconstructions were performed from January 1, 2005 to December 31, 2013. In the biliary transposition group (n=23), 5 reconstructions were performed using an internal stent (5 or 8 French pediatric feeding tube), and 18 were performed without. Of the 10 biliary ductoplasties, 2 were performed with a stent. All patients were managed with standard immunosuppression and ursodiol. Follow-up ranged from 2 months to 5 years. RESULTS: No patients in the biliary transposition group required reoperation; 1 patient had an internal stent removed for recurrent unexplained leukocytosis, and 2 patients required endoscopic retrograde cholangiography and stent placement for evidence of stricture. Three anastomotic leaks occurred in the biliary ductoplasty group, and 2 patients in the biliary ductoplasty group required reoperation for biliary complications. CONCLUSION: Our results indicate that biliary reconstruction can be performed with either biliary transposition or biliary ductoplasty. These techniques are particularly useful when a significant mismatch in diameter exists between the donor and recipient bile ducts.

7.
Ochsner J ; 17(1): 76-79, 2017.
Article in English | MEDLINE | ID: mdl-28331452

ABSTRACT

BACKGROUND: Portal vein thrombosis (PVT) is relatively common among candidates for liver transplantation and can present significant intraoperative challenges. Depending on the extent of PVT, thromboendovenectomy (TEV), portal bypass, or systemic inflow may be required to restore portal inflow. While TEV is the most commonly used approach to restore anatomic portal inflow, portal vein injury and life-threatening hemorrhage are risks with this technique. CASE REPORT: We present a salvage technique for managing portal vein injury during TEV using intraluminal balloon occlusion of the portal vein during portal vein repair and reconstruction. This alternative mode of bleeding control optimizes exposure to the retropancreatic space and avoids direct application of vascular clamps that can cause further injury to the vessel and surrounding tissue. CONCLUSION: Careful preoperative planning and anticipation of potential problems are essential for safe and effective management of complex PVT intraoperatively. The balloon-occlusion technique can facilitate safe and efficient repair of a portal vein injury during TEV for liver transplantation.

8.
Liver Transpl ; 23(3): 299-304, 2017 03.
Article in English | MEDLINE | ID: mdl-28026108

ABSTRACT

Liver transplantation (LT) offers the best chance of survival in selected patients with hepatocellular carcinoma (HCC). Wait-list mortality or dropout due to tumor progression can be significant, and therefore, timely transplantation is critical. Liver grafts discarded by outside organ procurement organizations are a potential source of grafts for low Model for End-Stage Liver Disease tumor patients. The primary aim of this study was to assess the disease-free and overall survival of patients with HCC transplanted with imported liver grafts (ILGs). Review of all patients transplanted for HCC between June 2005 and December 2014 was performed. Data on demographics, survival, and HCC recurrence were analyzed. During this time period, 59 out of 190 (31%) recipients with HCC received ILG. Of these 59 grafts, 54 were imported from within the region and 5 were from national offers (outside the region). The mean cold ischemia time for local liver grafts (LLGs) was 4.1 ± 1.5 hours versus 5.1 ± 1.4 hours for ILG (P < 0.001). The 1-, 3-, and 5-year patient survival was 90%, 85%, and 83% and 85%, 80%, and 79% for LLG and ILG (P = 0.08), respectively. The observed disease recurrence rate for both LLG and ILG recipients was equivalent. The median wait-list time for HCC recipients was 43 days (range, 2-1167 days). In conclusion, with careful graft assessment, the use of ILGs results in comparable outcomes following LT and no increased risk of HCC recurrence. Use of ILGs maximizes the donor pool and results in a higher rate of transplantation for HCC recipients. Liver Transplantation 23 299-304 2017 AASLD.


Subject(s)
Carcinoma, Hepatocellular/mortality , End Stage Liver Disease/mortality , Liver Neoplasms/mortality , Liver Transplantation/statistics & numerical data , Neoplasm Recurrence, Local/epidemiology , Tissue and Organ Procurement/methods , Adult , Aged , Allografts/pathology , Carcinoma, Hepatocellular/complications , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/surgery , Cold Ischemia/adverse effects , Donor Selection/methods , End Stage Liver Disease/etiology , End Stage Liver Disease/surgery , Female , Humans , Kaplan-Meier Estimate , Liver/pathology , Liver Neoplasms/complications , Liver Neoplasms/pathology , Liver Neoplasms/surgery , Male , Middle Aged , Neoplasm Staging , Patient Selection , Retrospective Studies , Severity of Illness Index , Time Factors , Treatment Outcome , United States/epidemiology , Waiting Lists/mortality
9.
J Cardiothorac Vasc Anesth ; 31(2): 575-581, 2017 Apr.
Article in English | MEDLINE | ID: mdl-27745797

ABSTRACT

OBJECTIVES: The purpose of this study was to compare the agreement between two heparin assays, Hepcon HMS plus/Kaolin-ACT and Anti-Xa, and their predictive power in detecting circulating heparin levels post-reperfusion of the liver graft when compared with thromboelastogram (TEG) r time ratio in patients undergoing orthotopic liver transplantation (OLT). DESIGN: Prospective, observational cohort study design. SETTING: Single center, university hospital. PARTICIPANTS: Thirty-eight consecutive adults who had undergone liver transplant. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Paired arterial blood samples were collected before surgical incision, 5 minutes after administration of an average dose of 2,054±771 units of intravenous unfractionated heparin before caval cross-clamping, 5 minutes after portal reperfusion, 5 minutes after hepatic artery reperfusion, and 1 hour after hepatic artery reperfusion. The observations that heparin assay measurements were within the predetermined limits of agreement, strongly suggested the two heparin assays (Hepcon HMS plus and Anti-Xa assay) are interchangeable during prophylactic heparin dose therapy during OLT. Post-reperfusion, receiver operating characteristic curve analysis revealed high accuracy in measuring circulating heparin levels with both Anti-Xa and Hepcon HMS assays when compared with the TEG r time ratio assay. CONCLUSIONS: The point-of-care Hepcon HMS plus/Kaolin-ACT (activated clotting time) assay appeared to be a reliable alternative to the more expensive and laboratory-required Anti-Xa assay in monitoring the response to intravenous heparin in patients undergoing OLT.


Subject(s)
Anticoagulants/administration & dosage , Factor Xa Inhibitors/administration & dosage , Heparin/administration & dosage , Liver Transplantation/methods , Plant Preparations/administration & dosage , Pre-Exposure Prophylaxis/methods , Adult , Aged , Anticoagulants/blood , Blood Coagulation Tests/methods , Cohort Studies , Female , Heparin/blood , Humans , Male , Middle Aged , Prospective Studies , Thrombelastography/methods
10.
Hepatobiliary Pancreat Dis Int ; 15(6): 587-592, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27919847

ABSTRACT

BACKGROUND: Split liver transplantation increases the number of grafts available for transplantation. Pre-recovery assessment of liver graft volume is essential for selecting suitable recipients. The purpose of this study was to determine the ability and feasibility of constructing a 3-D model to aid in surgical planning and to predict graft weight prior to an in situ division of the donor liver. METHODS: Over 11 months, 3-D volumetric reconstruction of 4 deceased donors was performed using Pathfinder Scout© liver volumetric software. Demographic, laboratory, operative, perioperative and survival data for these patients along with donor demographic data were collected prospectively and analyzed retrospectively. RESULTS: The average predicted weight of the grafts from the adult donors obtained from an in situ split procedure were 1130 g (930-1458 g) for the extended right lobe donors and 312 g (222-396 g) for left lateral segment grafts. Actual adult graft weight was 92% of the predicted weight for both the extended right grafts and the left lateral segment grafts. The predicted and actual graft weights for the pediatric donors were 176 g and 210 g for the left lateral segment grafts and 308 g and 280 g for the extended right lobe grafts, respectively. All grafts were transplanted except for the right lobe from the pediatric donors due to the small graft weight. CONCLUSIONS: On-site volumetric assessment of donors provides useful information for the planning of an in situ split and for selection of recipients. This information may expand the donor pool to recipients previously felt to be unsuitable due to donor and/or recipient weight.


Subject(s)
Imaging, Three-Dimensional/methods , Liver Transplantation/methods , Liver/anatomy & histology , Liver/surgery , Patient-Specific Modeling , Radiographic Image Interpretation, Computer-Assisted/methods , Tissue Donors/supply & distribution , Tomography, X-Ray Computed/methods , Adolescent , Adult , Child , Child, Preschool , Decision Support Techniques , Donor Selection , Feasibility Studies , Female , Humans , Liver Transplantation/adverse effects , Male , Middle Aged , Organ Size , Predictive Value of Tests , Retrospective Studies , Software , Treatment Outcome , Young Adult
11.
J Cardiothorac Vasc Anesth ; 30(4): 917-23, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27020101

ABSTRACT

OBJECTIVES: To examine the role of epsilon-aminocaproic acid (EACA) administered after reperfusion of the donor liver in the incidences of thromboembolic events and acute kidney injury within 30 days after orthotopic liver transplantation. One-year survival rates between the EACA-treated and EACA-nontreated groups also were examined. DESIGN: Retrospective, observational, cohort study design. SETTING: Single-center, university hospital. PARTICIPANTS: The study included 708 adult liver transplantations performed from 2008 to 2013. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: EACA administration was not associated with incidences of intracardiac thrombosis/pulmonary embolism (1.3%) or intraoperative death (0.6%). Logistic regression (n = 708) revealed 2 independent risk factors associated with myocardial ischemia (age and pre-transplant vasopressor use) and 8 risk factors associated with the need for post-transplant dialysis (age, female sex, redo orthotopic liver transplantation, preoperative sodium level, pre-transplant acute kidney injury or dialysis, platelet transfusion, and re-exploration within the first week after transplant); EACA was not identified as a risk factor for either outcome. One-year survival rates were similar between groups: 92% in EACA-treated group versus 93% in the EACA-nontreated group. CONCLUSIONS: The antifibrinolytic, EACA, was not associated with an increased incidence of thromboembolic complications or postoperative acute kidney injury, and it did not alter 1-year survival after liver transplantation.


Subject(s)
Acute Kidney Injury/etiology , Aminocaproic Acid/adverse effects , Antifibrinolytic Agents/adverse effects , Liver Transplantation/adverse effects , Thromboembolism/etiology , Aminocaproic Acid/administration & dosage , Antifibrinolytic Agents/administration & dosage , Dose-Response Relationship, Drug , Female , Humans , Liver Transplantation/mortality , Male , Middle Aged , Renal Replacement Therapy , Retrospective Studies , Risk Factors , Survival Analysis
12.
Ochsner J ; 15(3): 272-6, 2015.
Article in English | MEDLINE | ID: mdl-26413003

ABSTRACT

BACKGROUND: Vascular thrombosis is a well-known complication after simultaneous pancreas-kidney (SPK) transplantation procedures. The role of preoperative special coagulation studies to screen patients at high risk for vascular thrombosis is unclear and not well studied. METHODS: This study reports a retrospective medical record review of 83 SPK procedures performed between April 2007 and June 2013 in a single institution. All SPK transplantation recipients underwent preoperative screening for hypercoagulable state. RESULTS: Eighteen of 83 patients (21.69%) were diagnosed with vascular thrombosis of the pancreas. Of the 23 patients with at least 1 positive screening test, only 4 had a thrombotic event (17.39%). On the other hand, 14 of 60 patients with negative screening tests developed vascular thrombosis (23.33%). The hypercoagulable screening workup had a positive predictive value of 17.39% and a negative predictive value of 76.67%. The workup also demonstrated low sensitivity (22.22%) and specificity (70.77%). CONCLUSION: No differences were seen in patient or graft survival between groups at 12 months. This retrospective study did not show any benefit of using special coagulation studies to rule out patients at risk for vascular thrombosis after SPK transplantation.

13.
World J Hepatol ; 7(11): 1484-93, 2015 Jun 18.
Article in English | MEDLINE | ID: mdl-26085908

ABSTRACT

Obesity is on the rise worldwide. As a result, unprecedented rates of patients are presenting with end stage liver disease in the setting of non-alcoholic fatty liver disease (NAFLD) and are requiring liver transplantation. There are significant concerns that the risk factors associated with obesity and the metabolic syndrome might have a detrimental effect on the long term outcomes following liver transplantation. In general, short term patient and graft outcomes for both obese and morbidly obese patients are comparable with that of non-obese patients, however, several studies report an increase in peri-operative morbidity and increased length of stay. Continued studies documenting the long-term outcomes from liver transplantation are needed to further examine the risk of recurrent disease (NAFLD) and also further define the role risk factors such cardiovascular disease might play long term. Effective weight reduction in the post liver transplant setting may mitigate the risks associated with the metabolic syndrome long-term.

14.
Ochsner J ; 15(1): 19-24, 2015.
Article in English | MEDLINE | ID: mdl-25829876

ABSTRACT

BACKGROUND: The number of robotic operations performed with the da Vinci Surgical System has increased during the past decade. This system allows for greater maneuverability and control than hand-assisted laparoscopic procedures, resulting in less tissue manipulation and irritation. METHODS: We retrospectively analyzed the results of 100 consecutive robotic-assisted laparoscopic donor nephrectomies and compared them to our most recent 20 hand-assisted laparoscopic donor nephrectomies. RESULTS: Between May 2008 and June 2012, 120 laparoscopic donor nephrectomies were performed at Ochsner Clinic Foundation. Of those, 100 live kidney donors underwent robotic-assisted laparoscopic donor nephrectomies. Surgical time and hospital length of stay improved after the first 20 patients receiving robotic-assisted laparoscopic nephrectomies, which was considered the learning curve. Sixty percent of patients who underwent robotic-assisted laparoscopic donor nephrectomies were released on postoperative day 1 compared to 45% of patients who underwent hand-assisted laparoscopic techniques. CONCLUSION: In our experience, robotic-assisted laparoscopic donor nephrectomy resulted in decreased postoperative length of stay that decreased the global cost of the procedure and allowed our institution to admit more patients.

15.
Liver Transpl ; 21(3): 321-8, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25545787

ABSTRACT

Liver transplantation (LT) with donation after circulatory death (DCD) donors has been associated with a high rate of ischemic-type biliary strictures (ITBSs) and inferior graft survival. To investigate the impact of an intraoperative tissue plasminogen activator (tPA) on outcomes following DCD LT, we conducted a retrospective analysis of DCD LT at the Toronto General Hospital (TGH) and the Ochsner Medical Center (OMC). Between 2009 and 2013, 85 DCD LTs were performed with an intraoperative tPA injection (n = 30 at TGH, n = 55 at OMC), and they were compared with 33 DCD LTs without a tPA. Donor and recipient characteristics were similar in the 2 groups. There was no significant difference in the intraoperative packed red blood cell transfusion requirement (3.2 ± 3.4 versus 3.1 ± 2.3 U, P = 0.74). Overall, biliary strictures occurred less commonly in the tPA-treated group (16.5% versus 33.3%, P = 0.07) with a much lower rate of diffuse intrahepatic strictures (3.5% versus 21.2%, P = 0.005). After 1 and 3 years, the tPA group versus the non-tPA group had superior patient survival (97.6% versus 87.0% and 92.7% versus 79.7%, P = 0.016) and graft survival (96.4% versus 69.7% and 90.2% versus 63.6%, P < 0.001). In conclusion, a tPA injection into the hepatic artery during DCD LT reduces ITBSs and improves graft and patient survival without increasing the risk for bleeding.


Subject(s)
Cholestasis/prevention & control , Fibrinolytic Agents/administration & dosage , Ischemia/prevention & control , Liver Transplantation/adverse effects , Thrombolytic Therapy/methods , Tissue Donors , Tissue Plasminogen Activator/administration & dosage , Adult , Aged , Blood Loss, Surgical/prevention & control , Blood Transfusion , Cause of Death , Cholestasis/diagnosis , Cholestasis/etiology , Donor Selection , Female , Graft Survival , Hepatic Artery , Humans , Injections, Intra-Arterial , Ischemia/diagnosis , Ischemia/etiology , Kaplan-Meier Estimate , Male , Middle Aged , New Orleans , Ontario , Retrospective Studies , Risk Factors , Time Factors , Treatment Outcome , Young Adult
16.
PLoS One ; 9(9): e108616, 2014.
Article in English | MEDLINE | ID: mdl-25265476

ABSTRACT

PURPOSE: Chronic Hepatitis C Virus (HCV)-infected patients with liver cirrhosis (LC) respond poorly to interferon-alpha (IFN-α) and ribavirin (RBV) combination therapy, but the reason for this is unclear. We previously reported that HCV-infection induces endoplasmic reticulum (ER) stress and autophagy response that selectively down regulates the type I IFN-α receptor-1 (IFNAR1) and RBV transporters (CNT1 and ENT1), leading to IFN-α/RBV resistance. The goal of this study is to verify whether an increase in ER stress and autophagy response is also associated with the reduced expression of IFNAR1 and RBV transporters in chronic HCV-infected patients. METHODS: Primary human hepatocytes (PHH) were infected with cell culture grown HCV particles (JFH-ΔV3-Rluc). HCV replication was confirmed by the detection of viral RNA by RT-qPCR and HCV-core protein by Western blotting. The ER stress and autophagy response and expression of IFN receptors and RBV transporters in HCV infected PHH and liver tissues derived from patients were measured by Western blotting. RESULT: HCV infection of PHH showed impaired expression of IFNAR1, IFNγR1 (Type II IFN receptor) and RBV transporters but not IL10Rß (Type III IFN-λ receptor). ER stress markers (BiP, IRE1α and peIF2α) and autophagy response (LC3II, Beclin 1 and ATG5) were induced in HCV infected chronic liver disease (CLD) and LC patients. Liver biopsies (CLD) show a 50% reduced expression of IFNAR1 and RBV transporters. Furthermore, the expression of IFNAR1 and RBV transporters was impaired in almost all LC patients. CONCLUSION: HCV infection induces ER stress and autophagy response in infected PHH and chronically infected liver tissues. The expression of IFNAR1, IFNγR1 and RBV transporters were significantly impaired in CLD and cirrhotic livers. Our study provides a potential explanation for the reduced response rate of IFN-α and RBV combination therapy in HCV infected patients with liver cirrhosis.


Subject(s)
Hepacivirus/physiology , Hepatitis C, Chronic/metabolism , Hepatitis C, Chronic/virology , Liver Cirrhosis/metabolism , Liver Cirrhosis/virology , Receptor, Interferon alpha-beta/metabolism , Receptors, Interferon/metabolism , Autophagy , Biological Transport , Biopsy , Cells, Cultured , Down-Regulation , Endoplasmic Reticulum Stress , Ethanol/pharmacology , Fatty Acids, Nonesterified/pharmacology , Hepacivirus/drug effects , Hepatitis C, Chronic/pathology , Hepatocytes/drug effects , Hepatocytes/pathology , Hepatocytes/virology , Humans , Liver/pathology , Liver/virology , Liver Cirrhosis/pathology , Ribavirin , Virus Replication
17.
Ochsner J ; 13(3): 413-8, 2013.
Article in English | MEDLINE | ID: mdl-24052774

ABSTRACT

BACKGROUND: In 2005, the results published by the Scientific Registry of Transplant Recipients showed that Ochsner Clinic Foundation's patient and graft survival rates were statistically lower than expected, and the United Network for Organ Sharing Membership and Professional Standards Committee placed our center under peer review. METHODS: In response, patient outcomes prior to August 2005 were carefully reviewed in a transparent fashion and protocols were written to standardize treatments. We renewed the focus on patient-related outcomes and regulatory adherence and empowered frontline staff to express their views, allowing for real teamwork to develop. Multiple changes were implemented in the everyday running of the program. A quality assurance and performance improvement plan (QAPI) was initiated to improve outcomes. RESULTS: In 2012, the Ochsner liver transplant program became the largest liver transplant program in the United States by volume and in 2013 was awarded the prestigious CareChex award, acknowledging it as the number one program in terms of quality of care and outcomes for liver transplantation. CONCLUSION: The methodical application of this QAPI program achieved a remarkable transformation of the Ochsner liver transplant program and exemplifies what is possible with strong teamwork from dedicated and talented staff.

19.
Liver Transpl ; 19(6): 611-8, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23526668

ABSTRACT

The use of livers from hepatitis B surface antigen-negative (HBsAg- )/hepatitis B core antibody-positive (HBcAb+ ) donors in liver transplantation (LT) for HBsAg(-) /HBcAb- recipients is still controversial because of a lack of standard antiviral prophylaxis and long-term follow-up. We present our 13-year experience with the use of HBcAb+ donor livers in HBcAb- recipients. Patients received prophylaxis with hepatitis B immunoglobulin at the time of LT and then lamivudine daily. De novo hepatitis B virus (HBV) was defined as positive HBV DNA detection. Between January 1999 and December 2010, 1013 adult LT procedures were performed at our center. Sixty-four HBsAg- /HBcAb- patients (6.3%) received an HBsAg- /HBcAb+ liver. All donor sera were negative for HBcAb immunoglobulin M and HBV DNA. The mean follow-up was 48.8 ± 40.1 months (range = 1.2-148.8). Both the patient survival rates and the graft survival rates were 92.2% and 69.2% at 1 and 5 years, respectively. No graft losses or deaths were related to de novo HBV. Nine of the 64 patients (14.1%) developed de novo HBV. The mean time from LT to de novo HBV was 21.4 ± 26.1 months (range = 10.8-92.8 months). De novo HBV was successfully treated with adefovir or tenofovir. In conclusion, HBcAb+ allografts can be safely used in HBcAb- recipients without increased mortality or graft loss. Lifelong prophylaxis, continuous surveillance, and compliance are imperative for success. Should a de novo infection occur, our experience suggests that a variety of treatments can be employed to salvage the graft and obtain serum HBV DNA clearance.


Subject(s)
Hepatitis B/transmission , Liver Failure/therapy , Liver Transplantation/methods , Tissue Donors , Adult , Aged , DNA, Viral/isolation & purification , Female , Follow-Up Studies , Graft Survival , Hepatitis B/pathology , Hepatitis B Core Antigens/metabolism , Hepatitis B Surface Antigens/metabolism , Humans , Immunoglobulins/therapeutic use , Immunosuppressive Agents/therapeutic use , Lamivudine/therapeutic use , Liver/virology , Liver Failure/complications , Male , Middle Aged , Time Factors , Treatment Outcome
20.
Clin Transpl ; : 111-20, 2012.
Article in English | MEDLINE | ID: mdl-23721014

ABSTRACT

Liver transplantation has become the best and most durable treatment for both acute and chronic liver disease. Over 1400 liver transplants have been performed at the Ochsner Clinic since the first successful transplant in 1987. Since its inception, the program has gone through several changes and advancements and has become one of the largest liver transplant programs in the United States. We have helped evolve steroid sparing immunosuppression and the use of extended criteria, donor organs. Establishment of criteria for the selection of recipients for re-transplantation has resulted in better than expected short and long-term results. Our center has faced the challenge of Hurricane Katrina and overcome it. We have improved steadily in both outcomes and transplants performed. The Ochnser Clinic Liver Transplant program will continue to improve access and outcomes for all patients with liver disease.


Subject(s)
Liver Failure/mortality , Liver Failure/surgery , Liver Transplantation/mortality , Liver Transplantation/trends , Academic Medical Centers/statistics & numerical data , Cyclonic Storms/mortality , Death , Fatty Liver/mortality , Fatty Liver/surgery , Graft Rejection/drug therapy , Graft Rejection/mortality , Hepatectomy/mortality , Hepatectomy/standards , Hepatectomy/trends , Hepatitis B Antibodies/blood , Hepatitis B, Chronic/mortality , Humans , Immunosuppressive Agents/therapeutic use , Liver Transplantation/standards , Louisiana/epidemiology , Obesity, Morbid/mortality , Postoperative Complications/mortality , Reoperation/statistics & numerical data , Risk Factors , Seroepidemiologic Studies , Tissue Donors/statistics & numerical data
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