{"title":"Thank You to our reviewers","authors":"","doi":"10.1016/j.ajt.2024.12.003","DOIUrl":"https://doi.org/10.1016/j.ajt.2024.12.003","url":null,"abstract":"","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"25 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142990224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Assessing clinical benefits of live-attenuated vaccination in post-liver transplant patients: Analysis of breakthrough infections and natural boosters.","authors":"Masayoshi Shinjoh, Munehiro Furuichi, Yohei Yamada, Takuma Ohnishi, Mizuki Yaginuma, Ken Hoshino, Tetsuo Nakayama","doi":"10.1016/j.ajt.2024.07.005","DOIUrl":"10.1016/j.ajt.2024.07.005","url":null,"abstract":"<p><p>Recently, live-attenuated measles, rubella, varicella, and mumps vaccines have been administered to carefully selected post-liver transplant patients. Although attention has been focused on post-vaccination antibody titers and adverse events, the real-life clinical benefits remain unclear. A comprehensive analysis of breakthrough infections and natural boosters (asymptomatic cases with significant elevation in virus antibody titers) following immunization post-liver transplantation was conducted from 2002-2023, exploring the timing, frequency, correlation with domestic outbreaks, and degree of antibody elevation. During the median 10-year observation period among 68 post-liver transplant patients, breakthrough infections occurred only in chickenpox, with 7 mild cases (1 episode/64 person-years). A total of 59 natural booster episodes (1, 5, 20, and 33 for measles, rubella, chickenpox, and mumps, respectively) were observed, with incidence rates of 1 per 569, 110, 22, and 17 person-years, respectively. The timing of natural boosters closely correlated with domestic outbreaks (P < .05 in chickenpox and mumps), influenced by local vaccine coverage. The degree of antibody elevation was significantly higher in individuals with breakthrough infections than in those with natural boosters (P < .05). These findings suggest that immunization with live-attenuated vaccines for post-liver transplant patients has demonstrated clinical benefits. Furthermore, mass vaccination has a positive impact on post-transplant patient outcomes.</p>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":" ","pages":"189-197"},"PeriodicalIF":8.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141618763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Laure F Pittet, Renato Gualtieri, Charlotte M Verolet, Arnaud G L'Huillier, Barbara E Wildhaber, Valérie A McLin, Klara M Posfay-Barbe
{"title":"Long-term persistence of seroprotection against measles following measles-mumps-rubella vaccination administered before and after pediatric liver transplantation.","authors":"Laure F Pittet, Renato Gualtieri, Charlotte M Verolet, Arnaud G L'Huillier, Barbara E Wildhaber, Valérie A McLin, Klara M Posfay-Barbe","doi":"10.1016/j.ajt.2024.07.017","DOIUrl":"10.1016/j.ajt.2024.07.017","url":null,"abstract":"<p><p>Liver transplantation (LT) recipients are susceptible to infections, including measles. Concerns about the safety and efficacy of live-attenuated vaccines, such as the measles-mumps-rubella (MMR) vaccine, have led to hesitancy among providers in administering them to immunocompromised patients. This 9-year interventional study assessed seroprotection against measles following MMR vaccination in pediatric LT recipients. Of 119 participants enrolled, 60 (50%) were seroprotected against measles after transplantation. Among the 59 nonseroprotected participants, 56 fulfilled safety criteria and received MMR vaccination with a seroprotection rate of 90% (95% confidence interval [CI], 73%-98%) after a first dose, 95% (95% CI, 85%-99%) after primary vaccination with 1 to 3 doses, comparable to nonimmunocompromized populations. However, measles antibodies declined over time, suggesting the need for regular monitoring, and booster doses. Half of the vaccinees (26/53, 49%) subsequently lost seroprotection. Among them, 23 received additional doses of MMR, with a high seroconversion rate. At their last follow-up (median, 6.1 years; interquartile range, 3.0-8.1 after inclusion), 63% (95% CI, 49%-75%) of all vaccinees were seroprotected against measles. In conclusion, MMR vaccination in pediatric LT recipients offers seroprotection against measles, but long-term immunity should be monitored closely.</p>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":" ","pages":"170-180"},"PeriodicalIF":8.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141726523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hye-Mee Kwon, Jae Hwan Kim, Sung-Hoon Kim, In-Gu Jun, Jun-Gol Song, Deok-Bog Moon, Gyu-Sam Hwang
{"title":"Benefits of liver transplant in critically ill patients with acute-on-chronic liver failure: Implementation of an urgent living-donor program.","authors":"Hye-Mee Kwon, Jae Hwan Kim, Sung-Hoon Kim, In-Gu Jun, Jun-Gol Song, Deok-Bog Moon, Gyu-Sam Hwang","doi":"10.1016/j.ajt.2024.08.008","DOIUrl":"10.1016/j.ajt.2024.08.008","url":null,"abstract":"<p><p>We evaluated the liver transplantation (LT) criteria in acute-on-chronic liver failure (ACLF), incorporating an urgent living-donor LT (LDLT) program. Critically ill patients with a Chronic Liver Failure Consortium (CLIF-C) ACLF score (CLIF-C_ACLF_score) ≥65, previously considered unsuitable for LT, were included to explore the excess mortality threshold of the CLIF-C_ACLF_score (CLIF-C_ACLF_score_threshold). We followed 854 consecutive patients with ACLF (276 ACLF grade 2 and 215 ACLF grade 3) over 10 years among 4432 LT recipients between 2008 and 2019. For advanced ACLF patients without immediate deceased-donor (DD) allocation, an urgent LDLT program was expedited. The CLIF-C_ACLF_score_threshold was determined by the metrics of transplant survival benefit: >60% 1-year and >50% 5-year survival rate. In predicting post-LT mortality, the CLIF-C_ACLF_score outperformed the (model for end-stage liver disease-sodium) MELD-Na and (model for end-stage liver disease) MELD-3.0 scores but was comparable to the Sundaram ACLF-LT-mortality score. A CLIF-C_ACLF_score ≥65 (n = 54) demonstrated posttransplant survival benefits, with 1-year and 5-year survival rates of 66.7% and 50.4% (P < .001), respectively. Novel CLIF-C_ACLF_score_threshold for 1-year and 5-year mortalities was 70 and 69, respectively. A CLIF-C_ACLF_score-based nomogram for predicting survival probabilities, integrating cardiovascular disease, diabetes, and donor type (LDLT vs DDLT), was generated. This study suggests reconsidering the criteria for unsuitable LT with a CLIF-C_ACLF_score ≥65. Implementing a timely salvage LT strategy, and incorporating urgent LDLT, can enhance survival rates.</p>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":" ","pages":"150-163"},"PeriodicalIF":8.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141998930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Victoria Gorbacheva, Ran Fan, Brian Gaudette, William M Baldwin, Robert L Fairchild, Anna Valujskikh
{"title":"Marginal zone B cells are required for optimal humoral responses to allograft.","authors":"Victoria Gorbacheva, Ran Fan, Brian Gaudette, William M Baldwin, Robert L Fairchild, Anna Valujskikh","doi":"10.1016/j.ajt.2024.09.004","DOIUrl":"10.1016/j.ajt.2024.09.004","url":null,"abstract":"<p><p>Antibody-mediated rejection (AMR) is among the leading causes of graft failure in solid organ transplantation. However, AMR treatment options are limited by an incomplete understanding of the mechanisms underlying de novo donor-specific antibody (DSA) generation. The development of pathogenic isotype-switched DSA in response to transplanted allografts is typically attributed to follicular B cells undergoing germinal center reaction whereas the contribution of other B cell subsets has not been previously addressed. The current study investigated the role of recipient marginal zone B cells (MZ B cells) in DSA responses using mouse models of heart and renal allotransplantation. MZ B cells rapidly differentiate into antibody-secreting cells in response to allotransplantation. Despite the selective depletion of follicular B cells in heart allograft recipients, MZ B cells are sufficient for T-dependent IgM and early IgG DSA production. Furthermore, the presence of intact MZ B cell subset is required to support the generation of pathogenic isotype-switched DSA in renal allograft recipients containing donor-reactive memory helper T cells. These findings are the first demonstration of the role of MZ B cells in humoral alloimmune responses following solid organ transplantation and identify MZ B cells as a potential therapeutic target for minimizing de novo DSA production and AMR in transplant recipients.</p>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":" ","pages":"48-59"},"PeriodicalIF":8.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11734443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sarah Kemme, Jennifer D Canniff, Krystle M Garth, Shaobing Li, Krupa Mysore, Adriana Weinberg, Amy G Feldman
{"title":"Detection of viral RNA and DNA and immune response following administration of live attenuated measles and varicella vaccines in children with chronic liver disease.","authors":"Sarah Kemme, Jennifer D Canniff, Krystle M Garth, Shaobing Li, Krupa Mysore, Adriana Weinberg, Amy G Feldman","doi":"10.1016/j.ajt.2024.06.011","DOIUrl":"10.1016/j.ajt.2024.06.011","url":null,"abstract":"<p><p>Infections preventable by live virus vaccines are surging in the setting of decreased herd immunity. Many children with chronic liver diseases (CLDs) are unimmunized and at increased risk for infection due to guidelines recommending against live vaccines within 4 weeks pretransplant. This prospective study of 21 children with CLD and 13 healthy controls defined the timing of measles virus and varicella-zoster virus (VZV) RNA- and DNA-emia following vaccination and compared immune responses to measles and varicella vaccines in both groups. Measles virus RNA and VZV DNA real-time PCR were measured weekly following vaccination; measles virus RNA was undetectable in all by 14 days postvaccination, but VZV DNA, which can be managed with antivirals, was detected in 1 child in the CLD group at 21 days and 1 control at 28 days postvaccination. Humoral or cell-mediated vaccine response was 100% to measles virus and 94% to VZV in the CLD group postvaccination, whereas it was 100% to both vaccines in controls. Our pilot study suggests that both live vaccines can be safely and effectively administered up to 14 days prior to transplantation in children with CLD. We anticipate this will improve vaccination rates and thus decrease rates of vaccine-preventable infections in vulnerable children with CLD.</p>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":" ","pages":"181-188"},"PeriodicalIF":8.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141430916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mark Ly, Ngee-Soon Lau, Claude Dennis, Jinbiao Chen, Charles Risbey, Sarah Tan, Renfen Chen, Chuanmin Wang, Mark D Gorrell, Catriona McKenzie, James G Kench, Ken Liu, Geoffrey W McCaughan, Michael Crawford, Carlo Pulitano
{"title":"Long-term ex situ normothermic machine perfusion allows regeneration of human livers with severe bile duct injury.","authors":"Mark Ly, Ngee-Soon Lau, Claude Dennis, Jinbiao Chen, Charles Risbey, Sarah Tan, Renfen Chen, Chuanmin Wang, Mark D Gorrell, Catriona McKenzie, James G Kench, Ken Liu, Geoffrey W McCaughan, Michael Crawford, Carlo Pulitano","doi":"10.1016/j.ajt.2024.07.019","DOIUrl":"10.1016/j.ajt.2024.07.019","url":null,"abstract":"<p><p>Bile duct regeneration is hypothesized to prevent biliary strictures, a leading cause of morbidity after liver transplantation. Assessing the capacity for biliary regeneration may identify grafts as suitable for transplantation that are currently declined, but this has been unfeasible until now. This study used long-term ex situ normothermic machine perfusion (LT-NMP) to assess biliary regeneration. Human livers that were declined for transplantation were perfused at 36 °C for up to 13.5 days. Bile duct biopsies, bile, and perfusate were collected throughout perfusion, which were examined for features of injury and regeneration. Biliary regeneration was defined as new Ki-67-positive biliary epithelium following severe injury. Ten livers were perfused for a median duration of 7.5 days. Severe bile duct injury occurred in all grafts, and biliary regeneration occurred in 70% of grafts. Traditional biomarkers of biliary viability such as bile glucose improved during perfusion but this was not associated with biliary regeneration (P > .05). In contrast, the maintenance of interleukin-6 and vascular endothelial growth factor-A levels in bile was associated with biliary regeneration (P = .017 for both cytokines). This is the first study to demonstrate biliary regeneration during LT-NMP and identify a cytokine signature in bile as a novel biomarker for biliary regeneration during LT-NMP.</p>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":" ","pages":"60-71"},"PeriodicalIF":8.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141764573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alba Torija, Marie Matignon, Flavio Vincenti, Franc Casanova-Ferrer, Caroline Pilon, Anat R Tambur, Laura Donadeu, Elena Crespo, Delphine Kervella, Maria Meneghini, Irina B Torres, Florianne Hafkamp, Anna Martinez-Lacalle, Claudia Carrera, José Zúñiga, Amarpali Brar, Josep Cruzado, A Osama Gaber, Helen Lee, Robert A Montgomery, Mark Stegall, Maryvonnick Carmagnat, Cédric Usureau, Francesc Moreso, Philippe Grimbert, Oriol Bestard
{"title":"Anti-HLA serologic response to CD38-targeting desensitization therapy is challenged by peripheral memory B cells in highly sensitized kidney transplant candidates.","authors":"Alba Torija, Marie Matignon, Flavio Vincenti, Franc Casanova-Ferrer, Caroline Pilon, Anat R Tambur, Laura Donadeu, Elena Crespo, Delphine Kervella, Maria Meneghini, Irina B Torres, Florianne Hafkamp, Anna Martinez-Lacalle, Claudia Carrera, José Zúñiga, Amarpali Brar, Josep Cruzado, A Osama Gaber, Helen Lee, Robert A Montgomery, Mark Stegall, Maryvonnick Carmagnat, Cédric Usureau, Francesc Moreso, Philippe Grimbert, Oriol Bestard","doi":"10.1016/j.ajt.2024.08.004","DOIUrl":"10.1016/j.ajt.2024.08.004","url":null,"abstract":"<p><p>High human leukocyte antigen (HLA) sensitization limits access to compatible transplantation. New CD38-targeting agents have been shown to reduce anti-HLA antibodies, although with important interpatient variability. Thus, pretreatment identification of responder and nonresponder (NR) patients is needed for treatment decision-making. We analyzed 26 highly sensitized (HS) patients from 2 desensitization trials using anti-CD38 monoclonal antibodies. Hierarchical clustering identified 3 serologic responder groups: high responders, low responders, and NR. Spectral flow cytometry and functional HLA-specific memory B cell (mBC) assessment were first conducted on peripheral blood mononuclear cells and bone marrow samples from 16 patients treated with isatuximab (NCT04294459). Isatuximab effectively depleted bone marrow plasma cells, peripheral CD38-expressing plasmablasts, plasma cells, transitional B cells, and class-switch mBCs, ultimately reducing frequencies of HLA-specific immunoglobulin G (IgG)-producing mBCs. Multidimensional spectral flow cytometry with partial least squares discriminant analysis revealed that pretreatment abundance of specific circulating mBC phenotypes, especially CD38neg class-switch mBCs, accurately distinguished between high serologic responders and low responders or NR (AUC 0.958, 0.860-1.000, P = .009), who also displayed significantly lower frequencies of HLA-specific IgG-producing mBCs (P < .0001). This phenotypical mBC signature predicting response to therapy was validated in an external HS patient cohort (n = 10) receiving daratumumab (NCT04204980). This study identifies critical circulating mBC subset phenotypes that distinguish HS patients with successful serologic responses to CD38-targeting desensitization therapies, potentially guiding treatment decision-making.</p>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":" ","pages":"88-101"},"PeriodicalIF":8.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jesse D Schold, Timothy L Pruett, Elizabeth A Pomfret, Ty B Dunn
{"title":"The dangerous precedent of censoring scientific dissemination.","authors":"Jesse D Schold, Timothy L Pruett, Elizabeth A Pomfret, Ty B Dunn","doi":"10.1016/j.ajt.2024.09.002","DOIUrl":"10.1016/j.ajt.2024.09.002","url":null,"abstract":"<p><p>The American Transplant Congress (ATC) is the largest national transplant meeting in the United States jointly sponsored by the American Society of Transplantation and the American Society of Transplant Surgeons. The 2024 ATC was held in Philadelphia, Pennsylvania during which a number of peer-reviewed scientific abstracts were censored from the program by the Health Resources and Services Administration. These abstract presentations were redacted from the program for perceived conflict with current government policy effectively restricting dissemination of highly rated findings and discussion in a scientific forum. In this viewpoint, we describe the content of the abstracts that were withdrawn from the annual ATC meeting and the implications of this censorship by the Health Resources and Services Administration. We further consider the ramifications of this action for the prospective evaluation of government policy and the relationship of the contract agency with the transplant community in the context of ongoing discussions of modernizing the transplant system which has previously been critiqued for lack of transparency.</p>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":" ","pages":"27-31"},"PeriodicalIF":8.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Honoring the 20th anniversary of the first face transplant.","authors":"Lara C Pullen","doi":"10.1016/j.ajt.2024.11.010","DOIUrl":"10.1016/j.ajt.2024.11.010","url":null,"abstract":"","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":" ","pages":"2-4"},"PeriodicalIF":8.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}