Mise à jour le : 01-05-2017
Les derniers abstracts de la revue Transplantation - Current Issue : |
Date de mise en ligne : Jeudi 01 janvier 1970
Alexander, Stephen I.; Clayton, Philip A.; Chadban, Steven J.
Organ Transplantation in Australia
No abstract available
Date de mise en ligne : Jeudi 01 janvier 1970
Muller, Elmi
Research Highlights
No abstract available
Date de mise en ligne : Jeudi 01 janvier 1970
Laurie, Sonia J.; Ford, Mandy L.
Epigenetic Remodeling in Exhausted T Cells: Implications for Transplantation Tolerance
No abstract available
Date de mise en ligne : Jeudi 01 janvier 1970
Fung, John J.
Thomas Earl Starzl, MD, PhD, Transplant Pioneer, Polymath, Mentor, March 11th, 1926–March 4th, 2017
No abstract available
Date de mise en ligne : Jeudi 01 janvier 1970
Aronsohn, Andrew
Timing Is Everything: Managing Hepatitis C Virus in Liver Transplant Candidates
No abstract available
Date de mise en ligne : Jeudi 01 janvier 1970
Soubrane, Olivier
Laparoscopic Donor Hepatectomy: The Long and Winding Road
No abstract available
Date de mise en ligne : Jeudi 01 janvier 1970
Schlitt, Hans J.
One More Step Toward a Clinically Applicable Tolerance Induction Protocol in Solid Organ Transplantation?
No abstract available
Date de mise en ligne : Jeudi 01 janvier 1970
Werner, Jens M.; Adenugba, Akinbami; Protzer, Ulrike
Immune Reconstitution After HCV Clearance With Direct Antiviral Agents: Potential Consequences for Patients With HCC?
Abstract: Recent introduction of all-oral direct-acting antiviral (DAA) treatment has revolutionized care of patients with chronic hepatitis C virus infection. Because patients with different liver disease stages have been treated with great success including those awaiting liver transplantation, therapy has been extended to patients with hepatocellular carcinoma as well. From observational studies among compensated cirrhotic hepatitis C patients treated with interferon-containing regimens, it would have been expected that the rate of hepatocellular carcinoma occurrence is markedly decreased after a sustained virological response. However, recently 2 studies have been published reporting markedly increased rates of tumor recurrence and occurrence after viral clearance with DAA agents. Over the last decades, it has been established that chronic antigen stimulation during persistent infection with hepatitis C virus is associated with continuous activation and impaired function of several immune cell populations, such as natural killer cells and virus-specific T cells. This review therefore focuses on recent studies evaluating the restoration of adaptive and innate immune cell populations after DAA therapy in patients with chronic hepatitis C virus infection in the context of the immune responses in hepatocarcinogenesis.
Date de mise en ligne : Jeudi 01 janvier 1970
Debes, Jose D.; de Knegt, Robert J.; Boonstra, Andre
The Path to Cancer and Back: Immune Modulation During Hepatitis C Virus Infection, Progression to Fibrosis and Cancer, and Unexpected Roles of New Antivirals
Abstract: Hepatitis C virus (HCV) infection affects over 130 million individuals worldwide, and it is the number 1 reason for liver transplantation in the United States. HCV infection progresses in a slow chronic fashion eliciting a strong but ineffective immune response, mainly characterized by NK cell dysfunction and T cell exhaustion. The chronic hepatic inflammation leads to liver fibrosis, cirrhosis, and cancer in a significant number of patients. In recent years, groundbreaking research has led to the discovery of new HCV-specific direct-acting antivirals (DAAs), which have an unprecedented efficacy to clear the virus, and establish a sustained virological response. Indeed, curing HCV infection with an oral medication is now reality. The effects of DAAs in mitigating the HCV-related complications of liver fibrosis and cancer are yet largely unknown. Nonetheless, recent controversial reports suggest a potential increase in liver cancer recurrence upon use of DAAs. In the current article, we review the most important immune-mediated mechanisms underlying HCV chronicity and the development of liver fibrosis and cancer. Furthermore, we discuss recent concern on use of the new agents.
Date de mise en ligne : Jeudi 01 janvier 1970
Vinaixa, Carmen; Strasser, Simone I.; Berenguer, Marina
Disease Reversibility in Patients With Post-Hepatitis C Cirrhosis: Is the Point of No Return the Same Before and After Liver Transplantation? A Review
Abstract: Liver fibrosis can regress in patients with chronic hepatitis in whom the underlying cause of liver damage is adequately treated. Studies documenting this benefit have been mostly performed in the setting of viral hepatitis, particularly hepatitis C virus, where sustained viral response has been unequivocally shown to result in histological and clinical improvement. With the advent of the new IFN-free regimens, highly effective and safe even in those historically considered “difficult to treat and cure patients,†additional benefits have been documented in patients treated at advanced stages of disease, including improvement in liver function with hepatic “recompensation,†reduction of portal hypertension, and eventually avoidance of liver transplantation. Disease reversibility has been also demonstrated in the posttransplant setting and appears to be similar to what is observed in the nontransplant patient.
Date de mise en ligne : Jeudi 01 janvier 1970
Verna, Elizabeth C.; Brown, Robert S. Jr
HCV Antiviral Therapy in Liver Transplant Candidates and Recipients With Renal Insufficiency
Abstract: Hepatitis C virus (HCV) remains the leading indication for liver transplant in much of the world and has traditionally been associated with diminished posttransplant survival due to recurrent HCV-related liver disease. This field has been dramatically changed by the advent of safe and effective direct-acting antiviral therapy, such that most patients can be cured in the pretransplant or posttransplant setting. In addition, there are now direct-acting antiviral regimens specifically approved for use in patients with severe renal insufficiency. However, patients with pre or posttransplant severe renal insufficiency remain more difficult to treat, due to mechanisms of drug metabolism in hepatic and renal failure, as well as posttransplant drug-drug interactions. Treatment options are even more restricted in non-1 HCV genotypes. Because renal insufficiency is common among patients with HCV, with decompensated cirrhosis, and in the posttransplant setting, this difficult scenario is relatively common. However, ongoing development of pangenotypic regimens with improved safety profiles, as well as additional data on dosing and safety among patients with severe renal insufficiency, will continue to expand options for cure even in these most difficult to treat patients.
Date de mise en ligne : Jeudi 01 janvier 1970
Tapper, Elliot B.; Afdhal, Nezam H.; Curry, Michael P.
Before or After Transplantation? A Review of the Cost Effectiveness of Treating Waitlisted Patients With Hepatitis C
Abstract: All patients with chronic hepatitis C virus (HCV) infections can and should be treated.1-9 Though highly effective direct-acting antiviral therapies are costly, the price of a cure is a 1-time investment that is outweighed by future benefits. For clinicians caring for patients requiring liver transplant, the key question relates to the timing of treatment: before or after liver transplantation? On 1 hand, treating HCV often improves our patients' model for end-stage liver disease (MELD) score, decreasing costs, and potentially improving longevity by reducing our patients' risk of death and transplantation. On the other hand, there is a concern that the cured patient with decompensated cirrhosis will find themselves in “MELD purgatory†with nonprogressive liver disease but a poor quality of life. At the same time, some patients, such as those with hepatocellular carcinoma, will require liver transplant irrespective of their MELD meaning that pretransplant therapy cannot reduce costs in such settings. These important tradeoffs are often difficult reconcile for clinicians who care for patients awaiting liver transplant. Fortunately, guidance for navigating these competing concerns can be obtained from cost-effectiveness analyses. Herein, we review the available data on this approach to HCV therapy before or after liver transplant.
Date de mise en ligne : Jeudi 01 janvier 1970
Miller, Charles M.; Quintini, Cristiano; Dhawan, Anil; Durand, Francois; Heimbach, Julie K.; Kim-Schluger, Hyung Leona; Kyrana, Eirini; Lee, Sung-Gyu; Lerut, Jan; Lo, Chung-Mau; Pomfret, Elizabeth Anne
The International Liver Transplantation Society Living Donor Liver Transplant Recipient Guideline
Abstract: Living donor liver transplantation (LDLT) has been increasingly embraced around the world as an important strategy to address the shortage of deceased donor livers. The aim of this guideline, approved by the International Liver Transplantation Society (ILTS), is to provide a collection of expert opinions, consensus, and best practices surrounding LDLT. Recommendations were developed from an analysis of the National Library of Medicine living donor transplantation indexed literature using the Grading of Recommendations Assessment, Development and Evaluation methodology. Writing was guided by the ILTS Policy on the Development and Use of Practice Guidelines (www.ilts.org ). Intended for use by physicians, these recommendations support specific approaches to the diagnostic, therapeutic, and preventive aspects of care of living donor liver transplant recipients.
Date de mise en ligne : Jeudi 01 janvier 1970
Terrault, Norah A.; McCaughan, Geoff W.; Curry, Michael P.; Gane, Edward; Fagiuoli, Stefano; Fung, James Y. Y.; Agarwal, Kosh; Lilly, Les; Strasser, Simone I.; Brown, Kimberly A.; Gadano, Adrian; Kwo, Paul Y.; Burra, Patrizia; Samuel, Didier; Charlton, Michael; Pessoa, Mario G.; Berenguer, Marina
International Liver Transplantation Society Consensus Statement on Hepatitis C Management in Liver Transplant Candidates
No abstract available
Date de mise en ligne : Jeudi 01 janvier 1970
Terrault, Norah A.; Berenguer, Marina; Strasser, Simone I.; Gadano, Adrian; Lilly, Les; Samuel, Didier; Kwo, Paul Y.; Agarwal, Kosh; Curry, Michael P.; Fagiuoli, Stefano; Fung, James Y. Y.; Gane, Edward; Brown, Kimberly A.; Burra, Patrizia; Charlton, Michael; Pessoa, Mario G.; McCaughan, Geoff W.
International Liver Transplantation Society Consensus Statement on Hepatitis C Management in Liver Transplant Recipients
No abstract available
Date de mise en ligne : Jeudi 01 janvier 1970
Sawinski, Deirdre; Patel, Nikunjkumar; Appolo, Brenda; Bloom, Roy
Use of HCV+ Donors Does Not Affect HCV Clearance With Directly Acting Antiviral Therapy But Shortens the Wait Time to Kidney Transplantation
Background: Hepatitis C virus (HCV) infection is prevalent in the renal transplant population but direct acting antiviral agents (DAA) provide an effective cure of HCV infection without risk of allograft rejection.
Methods: We report our experience treating 43 renal transplant recipients with 4 different DAA regimens.
Results: One hundred percent achieved a sustained viral response by 12 weeks after therapy, and DAA regimens were well tolerated. Recipients transplanted with a HCV+ donor responded equally well to DAA therapy those transplanted with a kidney from an HCV− donor, but recipients of HCV+ organs experienced significantly shorter wait times to transplantation, 485 days (interquartile range, 228-783) versus 969 days (interquartile range, 452-2008; P = 0.02).
Conclusions: On this basis, we advocate for a strategy of early posttransplant HCV eradication to facilitate use of HCV+ organs whenever possible. Additional studies are needed to identify the optimal DAA regimen for kidney transplant recipients, accounting for efficacy, timing relative to transplant, posttransplant clinical outcomes, and cost.
Date de mise en ligne : Jeudi 01 janvier 1970
Sawinski, Deirdre; Lee, Dong H.; Doyle, Alden M.; Blumberg, Emily A.
Successful Posttransplant Treatment of Hepatitis C With Ledipasvir-Sofosbuvir in HIV+ Kidney Transplant Recipients
Background: Ledipasvir-sofosbuvir is effective at eradicating hepatitis C virus (HCV) infection in the general population and in HCV-monoinfected kidney transplant recipients, but there are no data to guide its use in human immunodeficiency virus/HCV coinfected kidney transplant patients.
Methods: We treated 6 human immunodeficiency virus/HCV coinfected kidney transplant recipients with ledipasvir-sofosbuvir at our 2 centers. All were infected with genotype 1 and 66% had received kidneys from HCV+ donors.
Results: All patients cleared the virus while on therapy and 100% have achieved a sustained virologic response at 12 weeks after completion of ledipasvir-sofosbuvir. Tacrolimus dosing required adjustment during and after ledipasvir-sofosbuvir therapy but antiretroviral regimens did not.
Conclusions: Ledipasvir-sofosbuvir was well tolerated. Although all patients in our series were treated posttransplant, the ideal timing of HCV therapy in this population is unknown, and the impact of HCV clearance on posttransplant outcomes is yet to be determined.
Date de mise en ligne : Jeudi 01 janvier 1970
Eisenberger, Ute; Guberina, Hana; Willuweit, Katharina; Bienholz, Anja; Kribben, Andreas; Gerken, Guido; Witzke, Oliver; Herzer, Kerstin
Successful Treatment of Chronic Hepatitis C Virus Infection With Sofosbuvir and Ledipasvir in Renal Transplant Recipients
Background: Treatment of chronic hepatitis C virus (HCV) infection after renal allograft transplantation has been an obstacle because of contraindications associated with IFN-based therapies. Direct-acting antiviral agents are highly efficient treatment options that do not require IFN and may not require ribavirin. Therefore, we assessed the efficacy and safety of sofosbuvir and ledipasvir in renal transplant patients with chronic HCV infection.
Methods: Fifteen renal allograft recipients with therapy-naive HCV genotype (GT) 1a, 1b, or 4 were treated with the combination of sofosbuvir and ledipasvir without ribavirin for 8 or 12 weeks. Clinical data were retrospectively analyzed for viral kinetics and for renal and liver function parameters. Patients were closely monitored for trough levels of immunosuppressive agents, laboratory values, and potential adverse effects.
Results: Ten patients (66%) exhibited a rapid virologic response within 4 weeks (HCV GT1a, n = 4; HCV GT1b, n = 6). The other 5 patients exhibited a virologic response within 8 (HCV GT 1b, n = 4) or 12 weeks (HCV GT4, n = 1). One hundred percent of patients exhibited sustained virologic response at week 12 after the end of treatment. Clinical measures of liver function improved substantially for all patients. Adverse events were scarce; renal transplant function and proteinuria remained stable. Importantly, dose adjustments for tacrolimus were necessary for maintaining sufficient trough levels.
Conclusions: The described regimen appears to be safe and effective for patients after renal transplant and is a promising treatment regimen for eradicating HCV in this patient population.
Date de mise en ligne : Jeudi 01 janvier 1970
Tapper, Elliot B.; Hughes, Michael S.; Buti, Maria; Dufour, Jean-Francois; Flamm, Steve; Firdoos, Saima; Curry, Michael P.; Afdhal, Nezam H.
The Optimal Timing of Hepatitis C Therapy in Transplant Eligible Patients With Child B and C Cirrhosis: A Cost-Effectiveness Analysis
Background: Ledipasvir (LDV)/sofosbuvir (SOF) has demonstrated high efficacy, safety, and tolerability in hepatitis C virus (HCV)-infected patients. There is limited data, however, regarding the optimal timing of therapy in the context of possible liver transplantation (LT).
Methods: We compared the cost-effectiveness of 12 weeks of HCV therapy before or after LT or nontreatment using a decision analytical microsimulation state-transition model for a simulated cohort of 10 000 patients with HCV Genotype 1 or 4 with Child B or C cirrhosis. All model parameters regarding the efficacy of therapy, adverse events and the effect of therapy on changes in model for end-stage liver disease (MELD) scores were derived from the SOLAR-1 and 2 trials. The simulations were repeated with 10 000 samples from the parameter distributions. The primary outcome was cost (2014 US dollars) per quality adjusted life year.
Results: Treatment before LT yielded more quality-adjusted life year for less money than treatment after LT or nontreatment. Treatment before LT was cost-effective in 100% of samples at a willingness-to-pay threshold of US $100 000 in the base-case and when the analysis was restricted to Child B alone, Child C, or MELD > 15. Treatment before transplant was not cost-effective when MELD was 6-10. In sensitivity analyses, the MELD after which treatment before transplant was cost-effective was 13 and the maximum cost of LDV/SOF therapy at which treatment before LT is cost-effective is US $177 381.
Conclusions: From a societal perspective, HCV therapy using LDV/SOF with ribavirin before LT is the most cost-effective strategy for patients with decompensated cirrhosis and MELD score greater than 13.
Date de mise en ligne : Jeudi 01 janvier 1970
Elfeki, Mohamed A.; Abou Mrad, Rachel; Modaresi Esfeh, Jamak; Zein, Nizar N.; Eghtesad, Bijan; Zervos, Xaralambos; Hanouneh, Ibrahim A.; O’Shea, Robert; Carey, William D.; Alkhouri, Naim
Sofosbuvir/Ledipasvir Without Ribavirin Achieved High Sustained Virologic Response for Hepatitis C Recurrence After Liver Transplantation: Two-Center Experience
Background: Current recommended regimens to treat patients with hepatitis C virus (HCV) infection after liver transplantation include the use of ribavirin (RBV). Limited data are available on the efficacy of RBV-free regimens posttransplant, particularly the use of sofosbuvir (SOF)/ledipasvir (LDV) without RBV in this patient population. We aimed to assess the efficacy and safety of SOF/LDV fixed-dose combination without RBV in patients with HCV recurrence posttransplant.
Methods: This is a retrospective study of 46 patients with HCV recurrence posttransplant. SOF/LDV without RBV was used for 12 weeks in patients with early-stage fibrosis (F0-F2) or for 24 weeks in those with advanced fibrosis (F3-F4) and/or cholestatic hepatitis. The primary endpoint was sustained virologic response at 12 weeks after the end of treatment. Secondary outcomes included relapse after treatment and adverse events.
Results: Forty-six patients, with a mean age of 62 ± 8 years, a median duration since time of transplant of 904 days (range, 78-3525 days), an HCV genotype 1, and a mean baseline viral load of 7.79 million IU/mL, were treated. Of these, 32 patients were treated for 12 weeks, and 14 patients were treated for 24 weeks. Twenty-five patients (54%) were treatment experienced (21 with interferon and 4 with SOF). All 46 patients (100%) achieved sustained virological response (SVR) 12. Neither virologic relapses nor serious adverse events were noted.
Conclusions: The combination of SOF/LDV without RBV for 12 or 24 weeks produced 100% SVR 12 in patients with HCV recurrence after liver transplantation. The use of RBV may not be necessary to achieve SVR in this patient population.
Date de mise en ligne : Jeudi 01 janvier 1970
Salazar, James; Saxena, Varun; Kahn, James G.; Roberts, John P.; Mehta, Neil; Volk, Michael; Lai, Jennifer C.
Cost-Effectiveness of Direct-Acting Antiviral Treatment in Hepatitis C–Infected Liver Transplant Candidates With Compensated Cirrhosis and Hepatocellular Carcinoma
Background: Hepatitis C virus (HCV)(+) donors represent an effective strategy to increase liver donor availability to HCV-infected recipients. However, many HCV(+) transplant candidates are now receiving treatment with direct-acting anti-viral (DAA) agents that lower the risk of posttransplant HCV recurrence but could make the patient ineligible for HCV(+) livers.
Methods: We compared pretransplant DAA treatment versus deferred DAA treatment using a cost-effectiveness decision analysis model to estimate incremental cost-effectiveness ratios (cost per quality-adjusted life year gained) from the societal perspective across a range of HCV(+) liver availability rates. For practical considerations, the population modeled was restricted to well-compensated HCV(+) cirrhotics listed for liver transplantation with hepatocellular carcinoma MELD exception points.
Results: Under base case conditions, the deferred DAA treatment strategy was found to be the “dominant†strategy. That is, it provided superior health outcomes at cost savings compared to the pretransplant DAA treatment strategy. The pretransplant DAA treatment strategy trended towards cost-effectiveness as HCV(+) donor liver availability declined. However, only in 1 scenario that was highly optimized for favorable outcomes in the pretransplant DAA treatment arm (low availability of HCV(+) organs, low cost of DAA treatment, high cost of HCV recurrence) was the incremental cost-effectiveness ratio associated with HCV DAA treatment before transplant less than US $150 000/quality-adjusted life-year gained.
Conclusions: Deferring HCV treatment until after liver transplant and maintaining access to the expanded pool of HCV(+) donors appears to be the most cost-effective strategy for well-compensated HCV-infected cirrhotics listed for liver transplantation with hepatocellular carcinoma, even in geographic areas of relatively low HCV(+) donor availability.
Date de mise en ligne : Jeudi 01 janvier 1970
Fernández Carrillo, Carlos; Crespo, Gonzalo; de la Revilla, Juan; Castells, LluÃs; Buti, Maria; Montero, José Luis; Fábrega, Emilio; Fernández, Inmaculada; Serrano-Millán, Cristina; Hernández, Victoria; Calleja, José Luis; Londoño, MarÃa-Carlota
Successful Continuation of HCV Treatment After Liver Transplantation
Background: Guidelines recommend that patients with hepatitis C virus (HCV)-related liver disease be treated for HCV before liver transplant (LT) to eliminate the virus before surgery. However, the unpredictability of donor organ availability may limit treatment duration. Interruption of HCV treatment with resumption post-LT is 1 potential solution which has not been investigated widely.
Methods: Patients from 5 clinical centers included in the large, national, noninterventional Hepa-C registry who started treatment with direct-acting antiviral agents while awaiting LT were identified retrospectively and followed up prospectively. Fifteen patients who had treatment interruptions around LT were identified.
Results: The majority of patients (12/15) received interferon-free regimens, most commonly sofosbuvir + daclatasvir (8/12), for a total of 24 weeks (13/15). Treatment was discontinued temporarily for a median of 5 (range, 2-33) days. Fourteen patients completing 12 weeks of follow-up achieved a sustained virological response. One patient who died before week 12 posttreatment achieved a response at posttreatment week 4. Treatment was generally well tolerated. Serious adverse events were recorded in 2 of 15 patients (anaemia in 1 patient; pneumonia in 1 patient); all arose after LT.
Conclusions: Resumption of direct-acting antiviral agent therapy after a temporary interruption around LT was highly effective, achieving sustained virological response in all patients who completed 12 weeks of posttreatment follow-up. Treatment was generally well tolerated pretransplantation and posttransplantation, with a low rate of serious adverse events. Such a strategy may offer an important new approach to the treatment of patients awaiting LT which may be assessed in future studies.
Date de mise en ligne : Jeudi 01 janvier 1970
Snelgrove, Sarah L.; Lo, Cecilia; Hall, Pam; Lo, Camden Y.; Alikhan, Maliha A.; Coates, P. Toby; Holdsworth, Stephen R.; Hickey, Michael J.; Kitching, A Richard
Activated Renal Dendritic Cells Cross Present Intrarenal Antigens After Ischemia-Reperfusion Injury
Background: The healthy kidney contains an extensive population of renal mononuclear phagocytes (RMPs), with substantial phenotypic and functional diversity. However, how this diverse population is affected by ischemia-reperfusion injury (IRI), an obligate part of renal transplantation, is not yet well understood. The aim of this study was to characterize the phenotypic and functional alterations in RMPs induced by IRI.
Methods: Renal mononuclear phagocytes were studied 24 and 72 hours after 30 minutes of renal ischemia or sham operation. Kidneys were digested and the phenotypes of renal leukocyte populations were analyzed via flow cytometry. Multiphoton microscopy was used to image renal dendritic cells (DCs) in vivo using CD11c reporter mice. The capacity of renal DCs to present antigen was examined by assessment of proliferation of ovalbumin-specific T cells in rat insulin promoter-membrane-bound ovalbumin transgenic mice after sham or IRI procedures.
Results: Ischemia-reperfusion injury induced influx of monocytes, DCs, macrophages, and neutrophils into the kidney. Classification of RMP subpopulations based on CD11b/CD11c expression demonstrated that the RMPs that increased in response to IRI were predominantly newly recruited monocyte-derived inflammatory DCs. In vivo multiphoton imaging of CD11c-EYFP mice revealed that intrarenal DCs exhibited increased number and activity of dendrites in the postischemic period. Ischemia-reperfusion injury also promoted DC-dependent cross-presentation of renal antigens to CD8+ T cells in the draining lymph node.
Conclusions: In response to renal IRI, RMP populations are skewed toward those derived from inflammatory monocyte precursors. In addition, renal DCs undergo functional activation, increasing their capacity to activate antigen-specific CD8+ T cells in renal draining lymph nodes.
Date de mise en ligne : Jeudi 01 janvier 1970
Villa, Chiara; Manzoli, Vita; Abreu, Maria M.; Verheyen, Connor A.; Seskin, Michael; Najjar, Mejdi; Molano, R. Damaris; Torrente, Yvan; Ricordi, Camillo; Tomei, Alice A.
Effects of Composition of Alginate-Polyethylene Glycol Microcapsules and Transplant Site on Encapsulated Islet Graft Outcomes in Mice
Background: Understanding the effects of capsule composition and transplantation site on graft outcomes of encapsulated islets will aid in the development of more effective strategies for islet transplantation without immunosuppression.
Methods: Here, we evaluated the effects of transplanting alginate (ALG)-based microcapsules (Micro) in the confined and well-vascularized epididymal fat pad (EFP) site, a model of the human omentum, as opposed to free-floating in the intraperitoneal cavity (IP) in mice. We also examined the effects of reinforcing ALG with polyethylene glycol (PEG). To allow transplantation in the EFP site, we minimized capsule size to 500 ± 17 μm. Unlike ALG, PEG resists osmotic stress, hence we generated hybrid microcapsules by mixing PEG and ALG (MicroMix) or by coating ALG capsules with a 15 ± 2 μm PEG layer (Double).
Results: We found improved engraftment of fully allogeneic BALB/c islets in Micro capsules transplanted in the EFP (median reversal time [MRT], 1 day) versus the IP site (MRT, 5 days; P < 0.01) in diabetic C57BL/6 mice and of Micro encapsulated (MRT, 8 days) versus naked (MRT, 36 days; P < 0.01) baboon islets transplanted in the EFP site. Although in vitro viability and functionality of islets within MicroMix and Double capsules were comparable to Micro, addition of PEG to ALG in MicroMix capsules improved engraftment of allogeneic islets in the IP site, but resulted deleterious in the EFP site, probably due to lower biocompatibility.
Conclusions: Our results suggest that capsule composition and transplant site affect graft outcomes through their effects on nutrient availability, capsule stability, and biocompatibility.
Date de mise en ligne : Jeudi 01 janvier 1970
Gerlach, Undine Ariane; Klöpfel, Maren; Atanasov, Georgi; Polenz, Dietrich; Vogt, Kathrin; Ahrlich, Stefanie; Marksteiner, Marion; Jurisch, Anke; Loddenkemper, Christoph; Reutzel-Selke, Anja; Sawitzki, Birgit; Pascher, Andreas
Intragraft and Systemic Immune Parameters Discriminating Between Rejection and Long-Term Graft Function in a Preclinical Model of Intestinal Transplantation
Background: The pathology and diagnosis of acute and chronic rejection in intestinal transplantation (ITX) are far from being completely understood. We established models of acute and chronic intestinal graft rejection and analyzed peripheral and intragraft immune responses.
Methods: We performed ITX from Dark Agouti into Lewis rats applying single-dose tacrolimus (TAC) at varying concentrations. Graft histology and immunohistology were assessed on postoperative day (POD)7, 14, and 45. Intragraft and peripheral gene expressions of inflammatory and anti-inflammatory markers and lipopolysaccharide binding protein (LBP) plasma as well as alloantibodies were measured simultaneously.
Results: A 1-mg TAC resulted in acute rejection and recipient death; 3 mg and 5 mg prolonged survival and led to severe or moderate chronic rejection, respectively, with 50% of the 5-mg TAC recipients surviving the observation period. Consequently, we observed severe infiltration on POD7 in untreated and 1-mg TAC recipients compared with minor histological alterations in 3 and 5 mg TAC groups. Only 5-mg TAC treatment prevented accumulation of CD4+ T cells and ED1+ macrophages over the entire observation period. Peripheral and intragraft expressions of T cell activation inhibitor—mitochondrial were stable in long-term surviving 5-mg TAC recipients but declined before acute or chronic rejection in 1 and 3 mg TAC recipients. In contrast, LBP levels increased during acute and chronic rejections.
Conclusions: We studied acute and chronic rejections in a preclinical model of ITX, which recapitulates clinical findings and highlights the importance of monitoring peripheral T cell activation inhibitor—mitochondrial expression, LBP levels, and antidonor antibodies for revealing rejection.
Date de mise en ligne : Jeudi 01 janvier 1970
Cantarelli, Elisa; Citro, Antonio; Pellegrini, Silvia; Mercalli, Alessia; Melzi, Raffaella; Dugnani, Erica; Jofra, Tatiana; Fousteri, Georgia; Mondino, Anna; Piemonti, Lorenzo
Transplant Site Influences the Immune Response After Islet Transplantation: Bone Marrow Versus Liver
Background: The aim of this study was to characterize the immune response against intrabone marrow (BM-Tx) or intraliver (liver-Tx) transplanted islets in the presence or in the absence of immunosuppression.
Methods: Less (C57BL/6 in Balb/c) and highly (Balb/c in C57BL/6) stringent major histocompatibility complex fully mismatched mouse models were used to evaluate the alloimmune response. Single antigen-mismatched mouse model (C57BL/6 RIP-GP in C57BL/6) was used to evaluate the antigen-specific immune response. Mice received tacrolimus (FK-506, 0.1 mg/kg per day)/mycophenolate mofetil (MMF, 60 mg/kg per day), and anti-CD3 (50 μg/day) either alone or in combination.
Results: Transplant site did not impact the timing nor the kinetics of the alloimmune and single antigen-specific memory T cell responses in the absence of immunosuppression or in the presence of MMF/FK-506 combination. On the other hand, the median time to graft rejection was 28 ± 5.2 days and 16 ± 2.6 days (P = 0.14) in the presence of anti-CD3 treatment, 50 ± 12.5 days and 10 ± 1.3 days (P = 0.003) in the presence of anti-CD3/MMF/FK-506 treatment for liver-Tx and BM-Tx, respectively. Anti-CD3 did not differentially reach BM and liver tissues but was more effective in reducing graft associated T cell responses in liver-Tx than in BM-Tx.
Conclusions: Islets infused in the BM appear less protected from the adaptive immune response in the presence of the anti-CD3 treatment. This result raises some concerns over the potential of the BM as a site for islet allotransplantation.
Date de mise en ligne : Jeudi 01 janvier 1970
Miyamoto, Ei; Motoyama, Hideki; Sato, Masaaki; Aoyama, Akihiro; Menju, Toshi; Shikuma, Kei; Sowa, Terumasa; Yoshizawa, Akihiko; Saito, Masao; Takahagi, Akihiro; Tanaka, Satona; Takahashi, Mamoru; Ohata, Keiji; Kondo, Takeshi; Hijiya, Kyoko; Chen-Yoshikawa, Toyofumi F.; Date, Hiroshi
Association of Local Intrapulmonary Production of Antibodies Specific to Donor Major Histocompatibility Complex Class I With the Progression of Chronic Rejection of Lung Allografts
Background: Antibody-mediated rejection may lead to chronic lung allograft dysfunction, but antibody-mediated rejection may develop in the absence of detectable donor-specific antibody (DSA) in recipient serum. This study investigated whether humoral immune responses develop not only systemically but locally within rejected lung allografts, resulting in local production of DSA.
Methods: Lewis rats received orthotopic left lung transplantation from Lewis (syngeneic control) or Brown-Norway (major histocompatibility complex-mismatched allogeneic) donor rats. Rats that underwent allogeneic lung transplantation were subsequently administered cyclosporine until day 14 (short immunosuppression) or day 35 (long immunosuppression). The lung grafts and spleens of recipient animals were tissue cultured for 4 days, and the titer of antibody against donor major histocompatibility complex molecules was assayed by flow cytometry. Explanted lung grafts were also evaluated pathologically.
Results: By day 98, DSA titers in supernatants of lung graft (P = 0.0074) and spleen (P = 0.0167) cultures, but not serum, from the short immunosuppression group were significantly higher than titers in syngeneic controls. Cultures and sera from the long immunosuppression group showed no production of DSA. Microscopically, the lung grafts from the short immunosuppression group showed severe bronchiole obliteration and parenchymal fibrosis, along with lymphoid aggregates containing T and B cells, accompanying plasma cells. These findings suggestive of local humoral immune response were not observed by days 28 and 63.
Conclusions: DSA can be locally produced in chronically rejected lung allografts, along with intragraft immunocompetent cells. Clinical testing of DSA in serum samples alone may underestimate lung allograft dysfunction.
Date de mise en ligne : Jeudi 01 janvier 1970
Xie, Yan; Wu, Yang; Xin, Kang; Wang, Jiao-Jing; Xu, Hong; Ildstad, Suzanne T.; Leventhal, Joseph; Yang, Guang-Yu; Zhang, Zheng; Levitsky, Josh
Delayed Donor Bone Marrow Infusion Induces Liver Transplant Tolerance
Background: Nonmyeloablative conditioning followed by donor bone marrow infusion (BMI) to induce tolerance has not been robustly tested in liver transplantation (LT) and may be unsafe at the time of LT. We hypothesized T cell–depleted BMI is effective in inducing tolerance when delayed after LT, resulting in potentially safer future clinical applications.
Methods: Nonimmunosuppressed syngeneic (Lewis to Lewis) and allogeneic (ACI to Lewis) rat LT transplants were initially performed as controls. Three experimental allogeneic LT groups were treated with tacrolimus (TAC) for 3 to 4 weeks and then underwent: (1) TAC withdrawal alone; (2) nonmyeloablative conditioning (anti-αβTCR mAb + total body irradiation [300 cGy]) followed by TAC withdrawal; (3) Nonmyeloablative conditioning + donor BMI (100 × 106 T cell–depleted bone marrow cells) followed by TAC withdrawal.
Results: All group 1 recipients developed chronic rejection. Group 2 had long-term survival but impaired liver function and high donor-specific antibody (DSA) levels. In contrast, group 3 (conditioning + BMI) had long-term TAC-free survival with preserved liver function and histology, high mixed chimerism and blood/liver/spleen CD4 + CD25 + Foxp3+ regulatory T cells, and low DSA titers, similar to syngeneic grafts. While donor-specific tolerance was observed post-BMI, graft-versus-host disease was not.
Conclusions: These results support that donor-specific tolerance can be achieved with BMI even when delayed after LT and this tolerance correlates with increased mixed chimerism, regulatory T cell generation, and diminished DSA.
Date de mise en ligne : Jeudi 01 janvier 1970
Goldberg, David S.; Karp, Seth J.; McCauley, Maureen E.; Markmann, James F.; Croome, Kristopher P.; Taner, C. Burcin; Heimbach, Julie K.; Leise, Michael D.; Fryer, Jonathan P.; Bohorquez, Humberto E.; Cohen, Ari J.; Gilroy, Richard K.; Kumer, Sean C.; Foley, David P.; Karim, Aos S.; Hernandez-Alejandro, Roberto; Levstik, Mark A.; Abt, Peter L.
Interpreting Outcomes in DCDD Liver Transplantation: First Report of the Multicenter IDOL Consortium
Background: In the United States, 5% of adult liver transplant recipients receive a graft donation after circulatory determination of death (DCDD). Concerns for ischemic cholangiopathy (IC), a disease of diffuse intrahepatic stricturing limits broader DCDD use. Single-center reports demonstrate large variation in outcomes.
Methods: Retrospective deidentified data collected between 2005 and 2013 were entered electronically by 10 centers via a Research Electronic Data Capture database. Our primary outcome was development of intrahepatic biliary strictures consistent with IC.
Results: Within 6 months post-DCDD transplant, 162 (21.8%) patients developed a biliary stricture, of which 88 (11.8%) exhibited intrahepatic structuring consistent with IC. Unadjusted 6-month IC rate among the 10 centers varied significantly (P = 0.006) from 6.3% to 25.9%. The only factor associated with increased risk of IC within 6 months was Roux-en-Y hepaticojejunostomy (vs duct-to-duct) (odds ratio, 3.06; 95% confidence interval, 1.52-6.16; P = 0.002). Graft failure by 6 months was more than 3 times higher for DCDD recipients with IC (odds ratio for IC, 3.36; 95% confidence interval, 1.95-5.79).
Conclusions: This first report of the large combined experience with DCDD from the Improving DCDD Outcomes in Liver Transplant consortium demonstrates significant differences in IC among centers, the importance of biliary strictures as a risk factor for graft failure, and does not validate other risk factors for IC found in smaller studies.
Date de mise en ligne : Jeudi 01 janvier 1970
Hirata, Yoshihiro; Yoshizawa, Atsushi; Egawa, Hiroto; Ueda, Daisuke; Okamoto, Shinya; Okajima, Hideaki; Yurugi, Kimiko; Hishida, Rie; Hirai, Hideyo; Miyagawa-Hayashino, Aya; Maekawa, Taira; Haga, Hironori; Uemoto, Sinji
Impact of Antibodies That React With Liver Tissue and Donor-Specific Anti-HLA Antibodies in Pediatric Idiopathic Posttransplantation Hepatitis
Background: The cause of late graft dysfunction has not been elucidated. Although an antibody-mediated reaction is suspected as a potential mechanism, the target antigens have not been clarified.
Methods: To clarify the etiology of idiopathic posttransplantation hepatitis (IPTH), we simultaneously examined the presence of antibodies that react with liver tissue (ARLT) by means of indirect immunofluorescence staining, as well as the presence of donor-specific anti-human leukocyte antigen antibodies (HLA-DSA). A subanalysis of the IPTH group was also performed. Within the IPTH group, the correlation between ARLT titer and clinical data were analyzed.
Results: In the sera of patients with IPTH (30 patients), ARLT were found at a significantly higher frequency than in patients without IPTH (42 patients; P < 0.001). Moreover, the ARLT titer appeared to be correlated with the severity of hepatitis or hepatic injury. In contrast, the frequency of HLA-DSA was significantly lower in patients with IPTH than in patients without IPTH (P = 0.001).
Conclusion: Our findings indicate that ARLT, and not HLA-DSA, profoundly influence the etiology of IPTH.
Date de mise en ligne : Jeudi 01 janvier 1970
Watson, Christopher J.E.; Kosmoliaptsis, Vasilis; Randle, Lucy V.; Gimson, Alexander E.; Brais, Rebecca; Klinck, John R.; Hamed, Mazin; Tsyben, Anastasia; Butler, Andrew J.
Normothermic Perfusion in the Assessment and Preservation of Declined Livers Before Transplantation: Hyperoxia and Vasoplegia—Important Lessons From the First 12 Cases
Background: A program of normothermic ex situ liver perfusion (NESLiP) was developed to facilitate better assessment and use of marginal livers, while minimizing cold ischemia.
Methods: Declined marginal livers and those offered for research were evaluated. Normothermic ex situ liver perfusion was performed using an erythrocyte-based perfusate. Viability was assessed with reference to biochemical changes in the perfusate.
Results: Twelve livers (9 donation after circulatory death [DCD] and 3 from brain-dead donors), median Donor Risk Index 2.15, were subjected to NESLiP for a median 284 minutes (range, 122-530 minutes) after an initial cold storage period of 427 minutes (range, 222-877 minutes). The first 6 livers were perfused at high perfusate oxygen tensions, and the subsequent 6 at near-physiologic oxygen tensions. After transplantation, 5 of the first 6 recipients developed postreperfusion syndrome and 4 had sustained vasoplegia; 1 recipient experienced primary nonfunction in conjunction with a difficult explant. The subsequent 6 liver transplants, with livers perfused at lower oxygen tensions, reperfused uneventfully. Three DCD liver recipients developed cholangiopathy, and this was associated with an inability to produce an alkali bile during NESLiP.
Conclusions: Normothermic ex situ liver perfusion enabled assessment and transplantation of 12 livers that may otherwise not have been used. Avoidance of hyperoxia during perfusion may prevent postreperfusion syndrome and vasoplegia, and monitoring biliary pH, rather than absolute bile production, may be important in determining the likelihood of posttransplant cholangiopathy. Normothermic ex situ liver perfusion has the potential to increase liver utilization, but more work is required to define factors predicting good outcomes.
Date de mise en ligne : Jeudi 01 janvier 1970
Bittermann, Therese; Goldberg, David S.; Bauer, Christina M.; Khungar, Vandana
Characterizing the Risk of False-Positive Hepatocellular Carcinoma in Recipients Transplanted With T2 MELD Exceptions
Background: Patients with hepatocellular carcinoma (HCC) can receive Model for End-Stage Liver Disease (MELD) exception points to increase waitlist priority for liver transplantation. This process does not require a biopsy and is based on radiologic criteria. However, imaging modalities are imperfect, and some will ultimately have no HCC on explant.
Methods: This was a retrospective cohort study using national explant pathology data from 2012 to 2015. False-positive HCC was defined as answering “no†to the question: “was evidence of HCC (viable or nonviable) found in the explant?†in patients with T2 MELD exceptions.
Results: Four thousand one hundred seventeen patients received T2 MELD exceptions, of which 245 (6%) had false-positive HCC. Maximal tumor diameter of 3 to 5 cm and serum α fetoprotein (AFP) greater than 100 ng/mL at transplant yielded a 50% lower risk of false-positive HCC (odds ratio [OR], 0.45; 95% confidence interval [CI], 0.27-0.73 and OR, 0.57; 95% CI, 0.37-0.88, respectively). Recipients with immune-mediated liver disease were twice as likely to have no HCC on explant (OR, 2.12; 95% CI, 1.18-3.83) and had a predicted probability of false positive HCC greater than 10% regardless of largest tumor size or AFP. Significant among-center variability in the rate of false-positive HCC was seen.
Conclusions: The risk of false-positive HCC is markedly higher in certain groups, such that biopsy may be warranted before T2 MELD exception point approval. Transplant centers with high false-positive HCC rates may benefit from greater oversight.
Date de mise en ligne : Jeudi 01 janvier 1970
Kim, Ki-Hun; Kang, Sung-Hwa; Jung, Dong-Hwan; Yoon, Young-In; Kim, Wan-Joon; Shin, Min-Ho; Lee, Sung-Gyu
Initial Outcomes of Pure Laparoscopic Living Donor Right Hepatectomy in an Experienced Adult Living Donor Liver Transplant Center
Background: Only a limited number of centers have performed laparoscopic living donor hepatectomy to date. In particular, laparoscopic right hepatectomy is rarely performed because the procedure can only be performed by surgeons with significant experience in both laparoscopic liver surgery and liver transplantation with living donor liver grafts.
Methods: Between November 2014 and February 2015, in a pure laparoscopic approach program for living right lobe donors at Asan Medical Center, 92 living donors underwent right hepatectomy for adult living donor liver transplantation. Among these, 3 pure laparoscopic living donor right hepatectomies were performed in 3 young female donors.
Results: The intraoperative and postoperative courses for all 3 donors and recipients were uneventful without any complications. Laparoscopic living donor hepatectomy has definite advantages over conventional open surgery, including decreased wound morbidity and faster recovery.
Conclusions: According to the data of the present report, pure laparoscopic living donor right hepatectomy in properly selected living donors (only 4% of potential donors in this cohort) appears to be a safe and feasible procedure in adult living donor liver transplantation.
Date de mise en ligne : Jeudi 01 janvier 1970
Aulbert, Wiebke; Kobbe, Robin; Breuer, Christian; Briem-Richter, Andrea; Schäfer, Hansjörg; Brinkert, Florian; Dettmar, Anne; Kemper, Markus Josef; Grabhorn, Enke
Hypereosinophilic Syndrome After Liver Transplantation: A Case Report and a Review of the Literature
Abstract: Persistently elevated eosinophil granulocytes in the peripheral blood in children is challenging because of a complex diagnosis especially after solid organ transplantation and can lead to difficulties in finding an underlying causative factor.
We report a 12-year-old boy who developed severe hypereosinophilia 11 years after liver transplantation due to biliary atresia. Accompanying symptoms were recurrent fever, fatigue, elevated liver enzymes, abdominal pain, and significant weight loss. After exclusion of secondary causes of eosinophilia, an idiopathic hypereosinophilic syndrome (I-HES) was diagnosed. Treatment with prednisolone resulted in an immediate response with rapid reduction of eosinophils, normalization of liver enzymes, and amelioration of any clinical symptoms. A hypereosinophilic syndrome in patients after liver transplantation is rare, and a broad differential diagnosis has to be considered. Prednisolone may lead to a prompt amelioration of eosinophilia and associated symptoms.
Date de mise en ligne : Jeudi 01 janvier 1970
Cheng, Xingxing S.; Stedman, Margaret R.; Chertow, Glenn M.; Kim, W. Ray; Tan, Jane C.
Utility in Treating Kidney Failure in End-Stage Liver Disease With Simultaneous Liver-Kidney Transplantation
Background: Simultaneous liver-kidney (SLK) transplantation plays an important role in treating kidney failure in patients with end-stage liver disease. It used 5% of deceased donor kidney transplanted in 2015. We evaluated the utility, defined as posttransplant kidney allograft lifespan, of this practice.
Methods: Using data from the Scientific Registry of Transplant Recipients, we compared outcomes for all SLK transplants between January 1, 1995, and December 3, 2014, to their donor-matched kidney used in kidney-alone (Ki) or simultaneous pancreas kidney (SPK) transplants. Primary outcome was kidney allograft lifespan, defined as the time free from death or allograft failure. Secondary outcomes included death and death-censored allograft failure. We adjusted all analyses for donor, transplant, and recipient factors.
Results: The adjusted 10-year mean kidney allograft lifespan was higher in Ki/SPK compared with SLK transplants by 0.99 years in the Model for End-stage Liver Disease era and 1.71 years in the pre-Model for End-stage Liver Disease era. Death was higher in SLK recipients relative to Ki/SPK recipients: 10-year cumulative incidences 0.36 (95% confident interval 0.33-0.38) versus 0.19 (95% confident interval 0.17-0.21).
Conclusions: SLK transplantation exemplifies the trade-off between the principles of utility and medical urgency. With each SLK transplantation, about 1 year of allograft lifespan is traded so that sicker patients, that is, SLK transplant recipients, are afforded access to the organ. These data provide a basis against which benefits derived from urgency-based allocation can be measured.
Date de mise en ligne : Jeudi 01 janvier 1970
Kamoun, Malek; McCullough, Keith P.; Maiers, Martin; Fernandez Vina, Marcelo A.; Li, Hongzhe; Teal, Valerie; Leichtman, Alan B.; Merion, Robert M.
HLA Amino Acid Polymorphisms and Kidney Allograft Survival
Background: The association of HLA mismatching with kidney allograft survival has been well established. We examined whether amino acid (AA) mismatches (MMs) at the antigen recognition site of HLA molecules represent independent and incremental risk factors for kidney graft failure (GF) beyond those MMs assessed at the antigenic (2-digit) specificity.
Methods: Data on 240 024 kidney transplants performed between 1987 and 2009 were obtained from the Scientific Registry of Transplant Recipients. We imputed HLA-A, -B, and -DRB1 alleles and corresponding AA polymorphisms from antigenic specificity through the application of statistical and population genetics inferences. GF risk was evaluated using Cox proportional-hazards regression models adjusted for covariates including patient and donor risk factors and HLA antigen MMs.
Results: We show that estimated AA MMs at particular positions in the peptide-binding pockets of HLA-DRB1 molecule account for a significant incremental risk that was independent of the well-known association of HLA antigen MMs with graft survival. A statistically significant linear relationship between the estimated number of AA MMs and risk of GF was observed for HLA-DRB1 in deceased donor and living donor transplants. This relationship was strongest during the first 12 months after transplantation (hazard ratio, 1.30 per 15 DRB1 AA MM; P < 0.0001).
Conclusions: This study shows that independent of the well-known association of HLA antigen (2-digit specificity) MMs with kidney graft survival, estimated AA MMs at peptide-binding sites of the HLA-DRB1 molecule account for an important incremental risk of GF.
Date de mise en ligne : Jeudi 01 janvier 1970
Kozakowski, Nicolas; Eskandary, Farsad; Herkner, Harald; Bond, Gregor; Oberbauer, Rainer; Regele, Heinz; Böhmig, Georg A.; Kikic, Željko
Diffuse Extent of Peritubular Capillaritis in Late Antibody-Mediated Rejection: Associations With Levels of Donor-Specific Antibodies and Chronic Allograft Injury
Background: Recently, diffuse peritubular capillaritis (ptc) has been suggested to independently predict chronic transplant injury and loss, and although the ptc score is a diagnostic criterion for antibody-mediated rejection, the utility of diffuse ptc is under debate.
Methods: We evaluated the diagnostic value of ptc characteristics in this cross-sectional study including 85 biopsies of patients with donor-specific antibodies (DSA). Biopsies were reevaluated for the extent (diffuse vs focal), score and leukocytic composition in relation to DSA binding strength (mean fluorescence intensity [MFI]_max). Chronic allograft injury (transplant chronic glomerulopathy [cg] or chronic lesion score CLS]) were associated with ptc features.
Results: Peritubular capillaritis was detected in 50% (76% mononuclear ptc). Peritubular capillaritis scores 1, 2, and 3 were present in 36%, 55%, and 9%, and focal or diffuse ptc in 36% or 64%. Diffuse ptc was associated with DSA MFI_max (median: 4407 vs 2419 [focal ptc; P = 0.04] or 1946 [no ptc; P = 0.004]), cg (58% vs no ptc 24% [P = 0.02]), and higher CLS (mean: 6.81 vs 4.67 [focal ptc, P = 0.01] or 5.18 [no ptc, P = 0.001]), respectively. The association of ptc score of 2 or greater with cg was slightly better than with diffuse ptc. Diffuse ptc and ptc score of 2 or greater remained independently related to cg after adjusting for DSA_MFI_max, C4d, or previous rejection episodes, however lost their independent relation after adjusting for total microcirculation scores. Diffuse ptc was the only ptc characteristic independently related to CLS.
Conclusions: Our results emphasize the clinical relevance of reporting diffuse ptc, which may relate to DSA binding strength and potentially to chronic graft injury.
Date de mise en ligne : Jeudi 01 janvier 1970
Hutchinson, James A.; Riquelme, Paloma; Bach, Christian; Kekarainen, Tuija; Fändrich, Fred; Geissler, Edward K.; Ahrens, Norbert
Donor-specific Anti-HLA Antibodies Present in Pooled Human Serum Do Not Prevent Development of Human Mreg_UKR From Monocytes in Culture
No abstract available
Date de mise en ligne : Jeudi 01 janvier 1970
Sönnerborg, Isabella V.; Höglund, Petter; Nordström, Johan; Wikman, Agneta; Wennberg, Lars; Nowak, Greg
Severe Transplantation-Mediated Alloimmune Thrombocytopenia in 2 Recipients of Organs From the Same Donor
No abstract available
Date de mise en ligne : Jeudi 01 janvier 1970
Singh, Neeraj; Dies, David; Samant, Hrishikesh
Hepatitis C–Positive Kidney Transplant Recipients—When Is The Best Time to Treat With Direct-Acting Antiviral Agents?
No abstract available
Date de mise en ligne : Jeudi 01 janvier 1970
Early Introduction of Subcutaneous Hepatitis B Immunoglobulin Following Liver Transplantation for Hepatitis B Virus Infection: A Prospective, Multicenter Study: Erratum
No abstract available