We investigated the prevalence and clinical outcomes of COVID-19 in recipients of kidney transplants in the Bronx, New York, one of the epicenters of the pandemic. Between March 16 and June 2, 2020, ...132 kidney transplant recipients tested positive by SARS-CoV-2 RT-PCR. From May 3 to July 29, 2020, 912 kidney transplant recipients were screened for SARS-CoV-2 IgG antibodies during routine clinic visits, of which 16.6% tested positive. Fifty-five of the 152 patients had previously tested positive by RT-PCR, while the remaining 97 did not have significant symptoms and had not been previously tested by RT-PCR. The prevalence of SARS-CoV-2 infection was 23.4% in the 975 patients tested by either RT-PCR or SARS-CoV-2 IgG. Older patients and patients with higher serum creatinine levels were more likely diagnosed by RT-PCR compared to SARS-CoV-2 IgG. Sixty-nine RT-PCR positive patients were screened for SARS-CoV-2 IgG antibodies at a median of 44 days post-diagnosis (Inter Quartile Range 31-58) and 80% were positive. Overall mortality was 20.5% but significantly higher (37.8%) in the patients who required hospitalization. Twenty-three percent of the hospitalized patients required kidney replacement therapy and 6.3% lost their allografts. In multivariable analysis, older age, receipt of deceased-donor transplantation, lack of influenza vaccination in the previous year and higher serum interleukine-6 levels were associated with mortality. Thus, 42% of patients with a kidney transplant and with COVID-19 were diagnosed on antibody testing without significant clinical symptoms; 80% of patients with positive RT-PCR developed SARS-CoV-2 IgG and mortality was high among patients requiring hospitalization.
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Backgound. Inconstant venous anatomy increases the risk of outflow complications in right hepatic live donor liver transplantation (RH-LDT), but no consensus has emerged guiding optimal ...reconstruction for venous outflow. Methods. We retrospectively analyzed surgical venous reconstruction using a flexible approach to anterior accessory veins in 48 RH-LDTs performed between April, 1998 and July, 2002. Results. Actuarial recipient graft and patient survival was 79% and 85%, respectively. Single hepatic venous anastomosis was performed in 74% of the patients. Twelve patients underwent reconstruction of 20 accessory veins, including 7 posterior segment veins and 13 anterior segment veins. Anterior vein reconstruction techniques included end-to-end anastomosis to the middle hepatic vein, interposition conduit, venoplasty, or a combination of techniques. Documented complications related to the venous anastomosis occurred in only 1 patient (2%), with no patient having a documented venous thrombosis of either the main RHV or a reconstructed accessory vein. There were no differences in outcome based on single versus multiple venous reconstruction. Anteromedial congestion was noted in 3 patients in the absence of anatomic venous anastomotic complication, but the clinical significance of this finding is unclear. Conclusions. Despite variations in segmental venous drainage and a propensity for anteromedial congestion in right hepatic grafts, RH-LDT can be performed without outflow obstruction with close attention to a wide RHV anastomosis. In addition, anterior accessory vein reconstruction can be reserved for grafts of marginal size or quality where early postoperative venous congestion may impair early graft function. Routine extended hepatectomy incorporating the MHV with the graft is unnecessary. (Surgery 2003;133:243-50.)
IMPORTANCE: Ischemic cold storage (ICS) of livers for transplant is associated with serious posttransplant complications and underuse of liver allografts. OBJECTIVE: To determine whether portable ...normothermic machine perfusion preservation of livers obtained from deceased donors using the Organ Care System (OCS) Liver ameliorates early allograft dysfunction (EAD) and ischemic biliary complications (IBCs). DESIGN, SETTING, AND PARTICIPANTS: This multicenter randomized clinical trial (International Randomized Trial to Evaluate the Effectiveness of the Portable Organ Care System Liver for Preserving and Assessing Donor Livers for Transplantation) was conducted between November 2016 and October 2019 at 20 US liver transplant programs. The trial compared outcomes for 300 recipients of livers preserved using either OCS (n = 153) or ICS (n = 147). Participants were actively listed for liver transplant on the United Network of Organ Sharing national waiting list. INTERVENTIONS: Transplants were performed for recipients randomly assigned to receive donor livers preserved by either conventional ICS or the OCS Liver initiated at the donor hospital. MAIN OUTCOMES AND MEASURES: The primary effectiveness end point was incidence of EAD. Secondary end points included OCS Liver ex vivo assessment capability of donor allografts, extent of reperfusion syndrome, incidence of IBC at 6 and 12 months, and overall recipient survival after transplant. The primary safety end point was the number of liver graft–related severe adverse events within 30 days after transplant. RESULTS: Of 293 patients in the per-protocol population, the primary analysis population for effectiveness, 151 were in the OCS Liver group (mean SD age, 57.1 10.3 years; 102 67% men), and 142 were in the ICS group (mean SD age, 58.6 10.0 years; 100 68% men). The primary effectiveness end point was met by a significant decrease in EAD (27 of 150 18% vs 44 of 141 31%; P = .01). The OCS Liver preserved livers had significant reduction in histopathologic evidence of ischemia-reperfusion injury after reperfusion (eg, less moderate to severe lobular inflammation: 9 of 150 6% for OCS Liver vs 18 of 141 13% for ICS; P = .004). The OCS Liver resulted in significantly higher use of livers from donors after cardiac death (28 of 55 51% for the OCS Liver vs 13 of 51 26% for ICS; P = .007). The OCS Liver was also associated with significant reduction in incidence of IBC 6 months (1.3% vs 8.5%; P = .02) and 12 months (2.6% vs 9.9%; P = .02) after transplant. CONCLUSIONS AND RELEVANCE: This multicenter randomized clinical trial provides the first indication, to our knowledge, that normothermic machine perfusion preservation of deceased donor livers reduces both posttransplant EAD and IBC. Use of the OCS Liver also resulted in increased use of livers from donors after cardiac death. Together these findings indicate that OCS Liver preservation is associated with superior posttransplant outcomes and increased donor liver use. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02522871
Hepatocyte Transplantation: Quo Vadis? Barahman, Mark; Asp, Patrik; Roy-Chowdhury, Namita ...
International journal of radiation oncology, biology, physics,
03/2019, Letnik:
103, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Orthotopic liver transplantation (OLT) has been effective in managing end-stage liver disease since the advent of cyclosporine immunosuppression therapy in 1980. The major limitations of OLT are ...organ supply, monetary cost, and the burden of lifelong immunosuppression. Hepatocyte transplantation, as a substitute for OLT, has been an exciting topic of investigation for several decades. HT is potentially minimally invasive and can serve as a vehicle for delivery of personalized medicine through autologous cell transplant after modification ex vivo. However, 3 major hurdles have prevented large-scale clinical application: (1) availability of transplantable cells; (2) safe and efficient ex vivo gene therapy methods; and (3) engraftment and repopulation efficiency. This review will discuss new sources for transplantable liver cells obtained by lineage reprogramming, clinically acceptable methods of genetic manipulation, and the development of hepatic irradiation-based preparative regimens for enhancing engraftment and repopulation of transplanted hepatocytes. We will also review the results of the first 3 patients with genetic liver disorders who underwent preparative hepatic irradiation before hepatocyte transplantation.
Studies comparing adult living donor liver transplantation to deceased donor liver transplantation have focused on post‐transplant survival. Our aim was to focus on the impact of living donor liver ...transplant on waiting time mortality and overall mortality. We analyzed the affect of living donor liver transplantation on waiting time mortality and overall mortality (from listing until last follow up) in a cohort of 116 transplant candidates. Fifty‐eight candidates who had individuals present as potential living donors (volunteer group) were matched by MELD score to 58 liver transplant candidates who did not have individuals present as a potential living donor (no volunteer group). Twenty‐seven percent of candidates in the no volunteer group and 62% of candidates in the volunteer group underwent liver transplantation, p = 0.0003. One‐year waiting list mortality for the volunteer group and no volunteer group was 10% and 20%, respectively, p = 0.03. Patient survival from the time of listing to last follow up was similar between the two groups. In our study group, living donor liver transplantation is associated with a higher rate of liver transplantation and lower waiting time mortality. In the era of living donor liver transplantation, estimates of patient survival should incorporate waiting time mortality.
Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide; its incidence is increasing in the United States. Depending on disease extent and underlying liver status, patients may be ...treated with local, locoregional, and/or systemic therapy. Recent data indicates that radiotherapy (RT) can play a meaningful role in the management of HCC. Here, we review published experiences using RT for HCC, including the use of radiosensitizers and stereotactic RT. We discuss methods for performing preclinical studies of RT for HCC and biomarkers of response. As a part of the HCC Working Group, an informal committee of the National Cancer Institute's Radiation Research Program, we suggest how RT should be implemented in the management of HCC and identify future directions for the study of RT in HCC.
Over the past decade we have reported excellent outcomes in pediatric living‐donor liver transplantation (LDLT) with recipient survival exceeding 90%. Principles established in these patients were ...extended to LDLT in adults. To compare outcomes in donors and recipients between adult and pediatric LDLT in a single center, we reviewed patient records of 45 LDLT performed between 1/98 and 2/01: 23 adult LDLT (54 ± 6.5 yr) and 22 pediatric LDLT (33.7 ± 53.5 months). Preoperative liver function was worse in adults (International Normalized Ratio INR 1.5 ± 0.4 vs. INR 1.2 ± 0.5; p = 0.032). 4 adults (17%) met criteria for status 1 or 2A. Only 1 child was transplanted urgently. Analysis included descriptive statistics and Kaplan‐Meier estimation. Donor mortality was 0% with 1 re‐exploration, 2.4%. Median hospital stay (LOS) was 6.0 days (range, 4–12 days). Donor morbidity and LOS did not differ by sex, extent of hepatectomy, or adult and pediatric LDLT (p = 0.49). In contrast, recipient outcomes were worse for adults. Adult 1 year graft survival was 65% (3 retransplants ReTx, 5 deaths) vs. 91% for children (1 ReTx, 1 death) p = 0.02. Graft losses in adults were due to sepsis (n = 3), small for size (n = 2), suicide, and hepatic artery thrombosis (HAT), whereas in children graft losses were due to portal thrombosis and total parenteral nutrition (TPN) liver failure. Biliary leaks occurred in 22% of adults and 9% of children. Hepatic vein obstruction occurred in 17% of adults and in none of the children. Median LOS was comparable (adult, 16.5 days (range, 7–149 days); child, 17 days (range, 10–56 days), p = 0.2). Graft function (total bilirubin (TBili) < 5mg/dl, INR < 1.2, aspartate aminotransferase (AST) < 100 U/l) normalizing by day 4 in children and by day 14 in adults. Adults fared worse, with an array of problems not seen in children, in particular, hepatic vein obstruction and small‐for‐size syndrome. Biliary leaks were diagnosed later in adults and were lethal in 3 cases; this was later avoided with biliary drainage in adult recipients. Finally, use of LDLT in decompensated adults led to death in 3 of 4 patients, and should be restricted to elective use.
Polycystic liver disease, commonly associated with polycystic kidney disease, can result in massive hepatomegaly and debilitating symptoms. Surgical intervention for symptomatic polycystic liver ...disease has been associated with significant morbidity and inconsistent long‐term palliation; it is more appropriate in patients with a single dominant cyst or cysts which is/are confined to one lobe. At our institution, nine patients have undergone orthotopic liver transplantation for symptomatic hepatic cysts with excellent long‐term results and minimal morbidity and mortality. Surgical candidates were selected based on severe limitations in daily activities and on sequelae of hepatic cystic involvement. Other factors considered were the extent and pattern of hepatic cystic disease, the degree of hepatic and renal dysfunction, and prior surgical intervention. Three patients (33%) required combined liver and kidney transplantation because of renal cystic involvement with renal insufficiency. The one‐year survival rate was 89% with excellent symptomatic relief and improved quality of life in all the surviving patients. One death occurred in a significantly malnourished 62‐year‐old female. Complications included one case each of hepatic artery thrombosis requiring retransplantation, biliary leak necessitating biliary reconstruction, and postoperative bleeding requiring re‐exploration. The mean hospital stay was 23 days and the mean intraoperative blood transfusion requirement was 18 units. Our experience demonstrates that appropriately selected patients with extensive hepatic involvement with adult polycystic liver disease can have an excellent outcome with transplantation, with morbidity comparable with other surgical options.
Hepatocellular cancer (HCC) is most common primary liver malignancy in adults. Treatment for HCC is a multispecialty undertaking, with surgical, locoregional, and systemic options available. Choice ...of treatment depends upon patient and disease factors. Surgical therapy, including resection and transplantation, is the primary curative treatment and is best suited to patients with early disease. More advanced disease may be amenable to locoregional therapies to “bridge” to transplantation, downstage disease, or as destination therapy for unresectable cases. These include percutaneous ablation, transarterial therapy, external radiation, and radioembolization with yttrium-90 conjugated beads. Patients with more advanced disease may benefit most from systemic chemotherapeutic or small molecule inhibitor options available, many of which have only been recently FDA approved. Immunotherapy is the newest component of HCC treatment. The Y-90 consultant should be familiar with all modalities of HCC treatment and the interplay between them.
Abstract
Background
Infections with multidrug resistant organisms (MDROs) are common in liver transplant recipients. We aimed to understand the prevalence and risk factors for MDRO infections during ...the peri-transplant period.
Methods
We conducted a retrospective chart review of adults ( >18 years) who underwent deceased donor liver transplant (LT) from Jan 2018-Dec 2020. Demographics and clinical information, including antibiotic use, microbiological data, and adequacy of perioperative antibiotics based on CLSI breakpoints, were reviewed. Peri-transplant period was defined as 12 months pre- and 3 months post-transplant. MDRO was defined as resistance to one or more classes of antibiotics. Statistical analysis was performed with IBM SPSS 29.0, using Chi2 or Fischer’s exact tests as appropriate for categorical variables and independent t-test for continuous variables.
Results
Baseline demographics for the 121 LT recipients are summarized in Table 1. In the 3 months post-transplant, 47 patients (38.8%) were noted to have positive cultures, of which 22 were MDRO. MDRO distribution for pre- and post-transplant infections is shown in Figure 1. Univariate analyses of predictors for post-transplant MDRO infection are shown in Table 2. Mean length of stay for patients with post-transplant MDRO infection was 65.3 days versus 28.6 days in those without MDRO infection (p< 0.001). Among 36 patients with positive cultures < 1month post-transplant, 55% (n=20) received perioperative antibiotics covering the identified organism. Eleven of 23 patients (47.8%) who received ampicillin-sulbactam (AS) and 3 of 8 patients (37.5%) who received piperacillin-tazobactam (PT) perioperatively developed infections not covered by their respective regimens < 1-month post-transplant. In the first month post-transplant, 17 patients had organisms cultured which were resistant to AS, of which all but one was also resistant to PT.Table 1Baseline Demographics
Conclusion
Admission to the intensive care unit, antibiotic use prior to transplant, and longer transplant hospitalizations were associated with MDRO infections. Tailoring of surgical prophylaxis may be indicated for high-risk patients as PT did not offer superior coverage over AS.
Disclosures
All Authors: No reported disclosures
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