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1.
Liver Transpl ; 28(6): 1039-1050, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34919762

RESUMO

Long-term humoral immunity and its protective role in liver transplantation (LT) patients have not been elucidated. We performed a prospective multicenter study to assess the persistence of immunoglobulin G (IgG) antibodies in LT recipients 12 months after coronavirus disease 2019 (COVID-19). A total of 65 LT recipients were matched with 65 nontransplanted patients by a propensity score including variables with recognized impact on COVID-19. LT recipients showed a lower prevalence of anti-nucleocapsid (27.7% versus 49.2%; P = 0.02) and anti-spike IgG antibodies (88.2% versus 100.0%; P = 0.02) at 12 months. Lower index values of anti-nucleocapsid IgG antibodies were also observed in transplantation patients 1 year after COVID-19 (median, 0.49 [interquartile range, 0.15-1.40] versus 1.36 [interquartile range, 0.53-2.91]; P < 0.001). Vaccinated LT recipients showed higher antibody levels compared with unvaccinated patients (P < 0.001); antibody levels reached after vaccination were comparable to those observed in nontransplanted individuals (P = 0.70). In LT patients, a longer interval since transplantation (odds ratio, 1.10; 95% confidence interval, 1.01-1.20) was independently associated with persistence of anti-nucleocapsid IgG antibodies 1 year after infection. In conclusion, compared with nontransplanted patients, LT recipients show a lower long-term persistence of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. However, SARS-CoV-2 vaccination after COVID-19 in LT patients achieves a significant increase in antibody levels, comparable to that of nontransplanted patients.


Assuntos
COVID-19 , Imunidade Humoral , Transplante de Fígado , Anticorpos Antivirais/sangue , COVID-19/imunologia , Vacinas contra COVID-19 , Humanos , Imunoglobulina G/sangue , Estudos Prospectivos , SARS-CoV-2
2.
Int J Mol Sci ; 23(22)2022 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-36430874

RESUMO

The nucleotide-binding domain leucine-rich repeat-receptor, pyrin domain-containing-3 (NLRP3) inflammasome contributes to the inflammatory response by activating caspase-1, which in turn participates in the maturation of interleukin (IL)-1ß and IL-18, which are mainly secreted via pyroptosis. Pyroptosis is a lytic type of cell death that is controlled by caspase-1 processing gasdermin D. The amino-terminal fragment of gasdermin D inserts into the plasma membrane, creating stable pores and enabling the release of several proinflammatory factors. The activation of NLRP3 inflammasome and pyroptosis has been involved in the progression of liver fibrosis and its end-stage cirrhosis, which is among the main etiologies for liver transplantation (LT). Moreover, the NLRP3 inflammasome is involved in ischemia-reperfusion injury and early inflammation and rejection after LT. In this review, we summarize the recent literature addressing the role of the NLRP3 inflammasome and pyroptosis in all stages involved in LT and argue the potential targeting of this pathway as a future therapeutic strategy to improve LT outcomes. Likewise, we also discuss the impact of graft quality influenced by donation after circulatory death and the expected role of machine perfusion technology to modify the injury response related to inflammasome activation.


Assuntos
Inflamassomos , Transplante de Fígado , Inflamassomos/metabolismo , Piroptose , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Caspase 1/metabolismo
3.
J Hepatol ; 74(1): 148-155, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32750442

RESUMO

BACKGROUND & AIMS: The incidence and outcomes of coronavirus disease 2019 (COVID-19) in immunocompromised patients are a matter of debate. METHODS: We performed a prospective nationwide study including a consecutive cohort of liver transplant patients with COVID-19 recruited during the Spanish outbreak from 28 February to 7 April, 2020. The primary outcome was severe COVID-19, defined as the need for mechanical ventilation, intensive care, and/or death. Age- and gender-standardised incidence and mortality ratios (SIR and SMR) were calculated using data from the Ministry of Health and the Spanish liver transplant registry. Independent predictors of severe COVID-19 among hospitalised patients were analysed using multivariate Cox regression. RESULTS: A total of 111 liver transplant patients were diagnosed with COVID-19 (SIR = 191.2 [95% CI 190.3-192.2]). The epidemiological curve and geographic distribution overlapped widely between the liver transplant and general populations. After a median follow-up of 23 days, 96 patients (86.5%) were admitted to hospital and 22 patients (19.8%) required respiratory support. A total of 12 patients were admitted to the ICU (10.8%). The mortality rate was 18%, which was lower than in the matched general population (SMR = 95.5 [95% CI 94.2-96.8]). Overall, 35 patients (31.5%) met criteria of severe COVID-19. Baseline immunosuppression containing mycophenolate was an independent predictor of severe COVID-19 (relative risk = 3.94; 95% CI 1.59-9.74; p = 0.003), particularly at doses higher than 1,000 mg/day (p = 0.003). This deleterious effect was not observed with calcineurin inhibitors or everolimus and complete immunosuppression withdrawal showed no benefit. CONCLUSIONS: Being chronically immunosuppressed, liver transplant patients have an increased risk of acquiring COVID-19 but their mortality rates are lower than the matched general population. Upon hospital admission, mycophenolate dose reduction or withdrawal could help in preventing severe COVID-19. However, complete immunosuppression withdrawal should be discouraged. LAY SUMMARY: In liver transplant patients, chronic immunosuppression increases the risk of acquiring COVID-19 but it could reduce disease severity. Complete immunosuppression withdrawal may not be justified. However, mycophenolate withdrawal or temporary conversion to calcineurin inhibitors or everolimus until disease resolution could be beneficial in hospitalised patients.


Assuntos
COVID-19/epidemiologia , Transplante de Fígado , Transplantados , Idoso , COVID-19/mortalidade , Inibidores de Calcineurina/uso terapêutico , Feminino , Hospitalização , Humanos , Terapia de Imunossupressão , Imunossupressores/uso terapêutico , Incidência , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Estudos Prospectivos , Espanha/epidemiologia
4.
Gastroenterol Hepatol ; 41(6): 406-421, 2018.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29866511

RESUMO

The goal of the Spanish Liver Transplantation Society (La Sociedad Española de Trasplante Hepático) is to promote and create consensus documents about current topics in liver transplantation with a multidisciplinary approach. To this end, on October 20, 2016, the 6th Consensus Document Meeting was held, with the participation of experts from the 24 authorized Spanish liver transplantation programs. This Edition discusses the following subjects, whose summary is offered below: 1) limits of simultaneous liver-kidney transplantation; 2) limits of elective liver re-transplantation; and 3) liver transplantation after resection and hepatocellular carcinoma with factors for a poor prognosis. The consensus conclusions for each of these topics is provided below.


Assuntos
Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Humanos
5.
Liver Transpl ; 23(7): 933-945, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28006867

RESUMO

Regulatory T cells (Tregs) play a potential role in operational tolerance in liver transplantation (LT) patients, and microRNAs (miRNAs) are known to be involved in immunological responses and tolerance. Thus, we analyzed the implication of different peripheral blood Treg subsets and miRNAs on LT tolerance in 24 tolerant (Tol) and 23 non-tolerant (non-Tol) LT recipients by cellular, genetic, and epigenetic approximation. Non-Tol patients had a lower demethylation rate of the forkhead box P3 (FOXP3) regulatory T cell-specific demethylated region (TSDR) than Tol patients that correlated with the frequency of circulating Tregs. Tol patients presented a different signature of Treg subset markers compared with non-Tol patients with increased expression of HELIOS and FOXP3 and a higher proportion of latency-associated peptide (LAP)+ Tregs and CD45RA- human leukocyte antigen D related (HLA-DR)+ activated effector-memory Tregs. The expression of miR95, miR24, miR31, miR146a, and miR155 was higher in Tol than in non-Tol patients and was positively correlated with activated Treg markers. In conclusion, these data suggest that activated effector-memory Tregs and a TSDR-demethylation state of Tregs may play a role in the complex system of regulation of LT tolerance. In addition, we describe a set of miRNAs differentially expressed in human LT Tol patients providing suggestive evidence that miRNAs are implied in the preservation of self-tolerance as mediated by Tregs. Liver Transplantation 23 933-945 2017 AASLD.


Assuntos
Transplante de Fígado , Ativação Linfocitária , MicroRNAs/análise , Linfócitos T Reguladores/imunologia , Tolerância ao Transplante , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise por Conglomerados , Desmetilação , Feminino , Fatores de Transcrição Forkhead/análise , Humanos , Masculino , MicroRNAs/fisiologia , Pessoa de Meia-Idade
6.
Transpl Int ; 30(10): 1041-1050, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28608619

RESUMO

Direct-acting antiviral agents (DAA) combining daclatasvir (DCV) have reported good outcomes in the recurrence of hepatitis C virus (HCV) infection after liver transplant (LT). However, its effect on the severe recurrence and the risk of death remains controversial. We evaluated the efficacy, predictors of survival, and safety of DAC-based regimens in a large real-world cohort. A total of 331 patients received DCV-based therapy. Duration of therapy and ribavirin use were at the investigator's discretion. The primary end point was sustained virological response (SVR) at week 12. A multivariate analysis of predictive factors of mortality was performed. Intention-to-treat (ITT) and per-protocol SVR were 93.05% and 96.9%. ITT-SVR was lower in cirrhosis (n = 163) (96.4% vs. 89.6% P = 0.017); the SVR in genotype 3 (n = 91) was similar, even in advanced fibrosis (96.7% vs. 88%, P = 0.2). Ten patients (3%) experienced virological failure. Therapy was stopped in 18 patients (5.44%), and ten died during treatment. A total of 22 patients (6.6%) died. Albumin (HR = 0.376; 95% CI 0.155-0.910) and baseline MELD (HR = 1.137; 95% CI: 1.061-1.218) were predictors of death. DCV-based DAA treatment is efficacious and safe in patients with HCV infection after LT. Baseline MELD score and serum albumin are predictors of survival irrespective of viral response.


Assuntos
Antivirais/uso terapêutico , Hepatite C/tratamento farmacológico , Imidazóis/uso terapêutico , Transplante de Fígado , Complicações Pós-Operatórias/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carbamatos , Feminino , Hepatite C/mortalidade , Hepatite C/virologia , Humanos , Terapia de Imunossupressão , Masculino , Pessoa de Meia-Idade , Pirrolidinas , Recidiva , Estudos Retrospectivos , Espanha/epidemiologia , Resposta Viral Sustentada , Valina/análogos & derivados
8.
Cir Esp ; 94(2): 77-85, 2016 Feb.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-26615737

RESUMO

BACKGROUND: Auxiliary heterotopic liver transplantation with portal vein arterialization (AHLT-PVA) is a model that has been hardly studied, despite its therapeutic potential. METHODS: Hemodynamic and biochemical characterization was carried out during graft implantation, in a pig-to-pig model (n=15 AHLT-PVA). Furthermore a histopathological study was performed to establish microscopic alterations due to PVA. RESULTS: Reperfusion of the arterialized graft produced an increase in heart rate (HR) vs. baseline (P=.004) and vs. inferior vena cava clamping phase (P=.004); and a decrease in systemic vascular resistance vs. cava clamping phase (P=.021). At the end of implantation, cardiac output remained elevated (P=.001), likewise HR remained increased vs. baseline phase (P=.002). Mean arterial pressure decreased with cava clamping, but was not affected by the reperfusion of the graft, nor the skin closure. The histopathological study at 3, 10, and 21 days post-PVA revealed that functional liver structure was maintained although it is common to find foci of perilobular necrosis on day 3 (P=.049), and perilobular connective tissue proliferation at day 10 (P=.007), vs. native liver. CONCLUSIONS: The described arterialized liver graft model minimizes the number of vascular anastomoses vs. previously described models. It is hemodynamically and metabolically well tolerated and the double arterial vascularization of the graft does not cause significant changes in liver histology.


Assuntos
Fígado/irrigação sanguínea , Animais , Hemodinâmica , Transplante de Fígado , Veia Porta , Suínos , Transplante Heterotópico
10.
Gastroenterol Hepatol ; 38(10): 600-18, 2015 Dec.
Artigo em Espanhol | MEDLINE | ID: mdl-26404045

RESUMO

With the aim to promote the elaboration of consensus documents on state of the art topics in liver transplantation with multidisciplinary management, the Spanish Society for Liver Transplantation (SETH) organized the V Consensus Meeting with the participation of experts from all the Spanish liver transplant programs. In this edition, the following topics were revised, and we present the summary: 1. High-risk receptors; 2. Immunosuppression scenarios; and 3. Management of the patient with hepatocarcinoma in the waiting list.


Assuntos
Doença Hepática Terminal/cirurgia , Transplante de Fígado , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/terapia , Terapia Combinada , Comorbidade , Rejeição de Enxerto/prevenção & controle , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Terapia de Imunossupressão/efeitos adversos , Terapia de Imunossupressão/métodos , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/terapia , Transplante de Fígado/métodos , Transplante de Fígado/normas , Obesidade/complicações , Seleção de Pacientes , Veia Porta , Cuidados Pré-Operatórios , Prognóstico , Risco , Sociedades Médicas , Espanha , Trombose Venosa/complicações , Listas de Espera
11.
Cir Esp ; 93(10): 619-37, 2015 Dec.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-26187597

RESUMO

With the aim to promote the elaboration of consensus documents on state of the art topics in liver transplantation with multidisciplinary management, the Spanish Society for Liver Transplantation (SETH) organized the V Consensus Meeting with the participation of experts from all the Spanish liver transplant programs. In this edition, the following topics were revised, and we present the summary: 1. High-risk receptors; 2. Immunosuppression scenarios; and 3. Management of the patient with hepatocarcinoma in the waiting list.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Consenso , Humanos , Listas de Espera
12.
Front Res Metr Anal ; 9: 1368534, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38550796

RESUMO

Background: Operational tolerance in liver transplantation (OT-LT), defined as the graft survival with normal function in absence of immunosuppression, has been a field of intense research since the 1980s. Thereafter, tens of clinical trials and hundreds of articles have been published, making it challenging for researchers to assimilate all the information, more so outside of their disciplines. The aim of the present study was to analyze the research in OT-LT through a new web tool (https://tolerance.imib.es). Methods: We have developed a web resource that allowed the identification of the present trends and potential research avenues in OL-LT, an overview biomedical terms that were most often cited, including which journals published the most articles, and an advanced search engine that exploited all the information in these publications. Results: A total of 734 studies were analyzed until November 2023, with a mean of 15 articles published per year, a total sum of 3,751 impact factor points and a total of 26,542 citations. The analysis of citations allowed us to establish a ranking of the most prolific countries, authors, journals and institutions, in addition to the most influential publications in OT-LT. Likewise, keyword and co-occurrence analyses answered which themes involving OT-LT are the most popular, whereas cooperation analysis showed that principal authors in OT-LT form a network, although the lack of international cooperation, especially with regard to clinical trials, appears to be one of the main challenges. Conclusion: Despite its limitations, our web tool will allow both OT-LT expert and novel researchers to be able to draw a comprehensive picture of the past, present and future of OT-LT research.

13.
Transplantation ; 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38578699

RESUMO

BACKGROUND: Liver transplantation (LT) is crucial for end-stage liver disease patients, but organ shortages persist. Donation after circulatory death (DCD) aims to broaden the donor pool but presents challenges. Complications like acute rejection, hepatic artery thrombosis, and biliary issues still impact posttransplant prognosis. Biomarkers, including extracellular vesicles (EVs) and microRNAs (miRNAs), show promise in understanding and monitoring posttransplant events. This study explores the role of EVs and their miRNA cargo in LT, including their potential as diagnostic tools. METHODS: EVs from intrahepatic end-ischemic organ preservation solution (eiOPS) in 79 donated livers were detected using different techniques (nanosight tracking analysis, transmission electron microscopy, and flow cytometry). EV-derived miRNAs were identified by quantitative real time-polymerase chain reaction. Bioinformatics analysis was performed using the R platform. RESULTS: Different-sized and origin-specific EVs were found in eiOPS, with significantly higher concentrations in DCD compared with donation after brain death organs. Additionally, several EV-associated miRNAs, including let-7d-5p, miR-28-5p, miR-200a-3p, miR-200b-3p, miR-200c-3p, and miR-429, were overexpressed in DCD-derived eiOPS. These miRNAs also exhibited differential expression patterns in liver tissue biopsies. Pathway analysis revealed enrichment in signaling pathways involved in extracellular matrix organization and various cellular processes. Moreover, specific EVs and miRNAs correlated with clinical outcomes, including survival and early allograft dysfunction. A predictive model combining biomarkers and clinical variables showed promise in acute rejection detection after LT. CONCLUSIONS: These findings provide new insights into the use of EVs and miRNAs as biomarkers and their possible influence on posttransplantation outcomes, potentially contributing to improved diagnostic approaches and personalized treatment strategies in LT.

14.
Liver Transpl ; 19(1): 69-77, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23008144

RESUMO

A sustained virological response (SVR) is achieved by 30% of naive liver transplantation (LT) recipients treated with pegylated interferon (PEG-IFN) and ribavirin (RBV). Almost no data are available about retreatment. The aim of this study was to assess the efficacy, tolerability, and SVR predictors of retreatment. Data were collected from 4 centers on the retreatment of prior nonresponders to standard therapy or PEG-IFN (with or without RBV) and relapsers. Seventy-nine of 301 treatment-experienced LT patients (26%), who had a median age of 59 years (range = 35-77 years) and were mostly male (72%) and infected with genotype 1 (87%), were retreated with PEG-IFN and RBV at a median of 6.9 years after LT. During the first course of therapy, 35% were treated with interferon, 49% received tacrolimus, 52% received steroids, and 49.5% were relapsers. Retreatment was started at a median of 1.9 years (range = 45 days to 8.2 years) after the end of the first course. The proportion of patients with cirrhosis increased from 10% to 37% (P < 0.001). In addition, in retreated patients, full initial RBV doses (P = 0.03), growth factors [erythropoietin (P < 0.001) and granulocyte colony-stimulating factor (P = 0.048)], and transfusions (P = 0.03) were used more frequently, and the treatment duration was longer (P = 0.03). An end-of-treatment response was achieved in 61%, whereas SVR, which was associated with improved survival, occurred in 28 (35%). The variables predicting SVR were age (P = 0.04), disease severity [fibrosis (50% with F0-F2 versus 26% with F3-4), P = 0.03; bilirubin, P = 0.006; platelet count, P = 0.03], adherence, and viral kinetics. None of the patients without an early virological response achieved SVR. There was a trend of prior relapsers achieving higher SVR rates than prior nonresponders. In conclusion, SVR, which was achieved by approximately one-third of the retreated patients, can be predicted with the same variables used for naive LT recipients (age, disease severity, adherence, and viral kinetics) and is associated with enhanced survival.


Assuntos
Hepatite C/tratamento farmacológico , Transplante de Fígado/efeitos adversos , Adulto , Idoso , Feminino , Hepatite C/mortalidade , Hepatite C/virologia , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/administração & dosagem , Proteínas Recombinantes/administração & dosagem , Ribavirina/administração & dosagem
15.
Biomedicines ; 11(9)2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37760846

RESUMO

Decompensated cirrhosis is the most common cause of ascites due to hemodynamic and renal alteration by continuous fluid leakage from the hepatic sinusoids and splanchnic capillaries into the interstitial space. Then, fluid leakage exceeds lymphatic return, leading to progressive fluid accumulation directly into the peritoneal cavity. Alcohol consumption is one of the main risks of developing alcoholic cirrhosis (AC), but not all AC patients develop ascites. Avoiding the development of ascites is crucial, given that it deteriorates prognosis and increases the patient mortality patient. The innate immune system plays a crucial role in cirrhosis through natural killer cells, which are abundant in the liver. The aim of this study was to analyze the KIR/HLA-C genetic profile in AC patients with and without ascites to understand this pathology and find predictive clinical susceptibility biomarkers that can help to establish risks and prevent the development of ascites in AC patients. A total of 281 AC patients with and without ascites were analyzed and compared with 319 healthy controls. Genomic DNA was extracted from peripheral blood in all groups. A PCR-SSO assay was performed for KIR/HLA genotyping analysis. A total of 16 activating and inhibitor KIR genes and their corresponding known ligands, epitopes of HLA-C, and their genotypes were analyzed. According to our analysis, C1 epitopes were statistically significantly decreased in AC patients with and without ascites. When comparing AC patients with ascites and healthy controls, a significant decrease in C1 epitope frequency was also observed. A statistically significant decrease was also found when comparing the C1C2 genotype in AC patients without ascites with controls. In conclusion, the absence of KIR2DL2 and KIR3DL1 genes may be a predisposing factor for the development of ascites in AC patients. The KIR2DS2/KIR2DL2 may could be involved in grade I ascites development, and the presence of the C1+ epitope and the homozygous C2C2 genotype may be protective genetic factors against ascites development in AC patients.

16.
Surgery ; 173(4): 1072-1078, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36549975

RESUMO

BACKGROUND: Postoperative complications of surgical incisions are frequent in liver transplantation. However, evidence justifying the use of incisional negative pressure wound therapy to improve surgical wound outcomes remains limited. METHODS: Participating patients were randomly assigned to receive incisional negative pressure wound therapy or standard surgical dressing on the closed surgical incision of the liver transplantation. The primary endpoint was surgical site infection incidence 30 days postoperatively. The secondary endpoints included surgical site events (ie, surgical site infection, dehiscence, hematoma, and seroma) and wound quality of life. RESULTS: Between December 2018 and September 2021, 108 patients (54 in the incisional negative pressure wound therapy group and 54 in the control group) were enrolled in this study. The incidence of surgical site infection at 30 days postoperatively was 7.4% in the treatment group and 13% in the control group (P = .34). The rate of surgical site events was similar in the treatment in the and control group (27.8% vs 29.6%, P = .83). In relation to wound quality of life, the mean score was 75.20 ± 7.27 in the incisional negative pressure wound therapy group and 72.82 ± 10.57 in the control group (P = .23). CONCLUSION: The prophylactic use of negative pressure wound therapy on primarily closed incisions did not significantly reduce incisional surgical site infection and surgical site event rates after liver transplantation compared with standard surgical dressings.


Assuntos
Transplante de Fígado , Tratamento de Ferimentos com Pressão Negativa , Ferida Cirúrgica , Humanos , Ferida Cirúrgica/terapia , Infecção da Ferida Cirúrgica/epidemiologia , Qualidade de Vida
17.
Cancers (Basel) ; 15(7)2023 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-37046783

RESUMO

BACKGROUND: Transarterial radioembolization in HCC for LT as downstaging/bridging has been increasing in recent years but some indication criteria are still unclear. METHODS: We conducted a systematic literature search of primary research publications conducted in PubMed, Scopus and ScienceDirect databases until November 2022. Relevant data about patient selection, HCC features and oncological outcomes after TARE for downstaging or bridging in LT were analyzed. RESULTS: A total of 14 studies were included (7 downstaging, 3 bridging and 4 mixed downstaging and bridging). The proportion of whole liver TARE was between 0 and 1.6%. Multiple TARE interventions were necessary for 16.7% up to 28% of the patients. A total of 55 of 204 patients across all included studies undergoing TARE for downstaging were finally transplanted. The only RCT included presents a higher tumor response with the downstaging rate for LT of TARE than TACE (9/32 vs. 4/34, respectively). Grade 3 or 4 adverse effects rate were detected between 15 and 30% of patients. CONCLUSIONS: TARE is a safe therapeutic option with potential advantages in its capacity to necrotize and reduce the size of the HCC for downstaging or bridging in LT.

18.
J Clin Invest ; 118(8): 2845-57, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18654667

RESUMO

A fraction of liver transplant recipients are able to discontinue all immunosuppressive therapies without rejecting their grafts and are said to be operationally tolerant to the transplant. However, accurate identification of these recipients remains a challenge. To design a clinically applicable molecular test of operational tolerance in liver transplantation, we studied transcriptional patterns in the peripheral blood of 80 liver transplant recipients and 16 nontransplanted healthy individuals by employing oligonucleotide microarrays and quantitative real-time PCR. This resulted in the discovery and validation of several gene signatures comprising a modest number of genes capable of identifying tolerant and nontolerant recipients with high accuracy. Multiple peripheral blood lymphocyte subsets contributed to the tolerance-associated transcriptional patterns, although NK and gammadeltaTCR+ T cells exerted the predominant influence. These data suggest that transcriptional profiling of peripheral blood can be employed to identify liver transplant recipients who can discontinue immunosuppressive therapy and that innate immune cells are likely to play a major role in the maintenance of operational tolerance in liver transplantation.


Assuntos
Perfilação da Expressão Gênica , Tolerância Imunológica , Transplante de Fígado/imunologia , Imunologia de Transplantes/genética , Tolerância ao Transplante/genética , Adulto , Idoso , Antígenos CD4/genética , Estudos de Casos e Controles , Estudos de Coortes , DNA/genética , DNA Viral/genética , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/genética , Rejeição de Enxerto/imunologia , Hepacivirus/genética , Hepacivirus/patogenicidade , Humanos , Imunofenotipagem , Imunossupressores/administração & dosagem , Células Matadoras Naturais/imunologia , Transplante de Fígado/patologia , Pessoa de Meia-Idade , Modelos Genéticos , Modelos Imunológicos , Análise de Sequência com Séries de Oligonucleotídeos , Valor Preditivo dos Testes , Receptores de Antígenos de Linfócitos T gama-delta/genética , Transcrição Gênica
19.
Gastroenterol Hepatol ; 34(3): 155-69, 2011 Mar.
Artigo em Espanhol | MEDLINE | ID: mdl-21376423

RESUMO

The liver is a privileged organ and has a lower incidence of rejection than other organs. However, immunosuppressive regimens are still required to control the alloreactive T-lymphocyte response after transplantation. These treatments may lead to severe complications, such as infectious diseases, cancers, cardiovascular diseases and chronic renal insufficiency. In clinical transplantation there is increasing evidence that some liver transplant recipients who cease taking immunosuppressive (IS) drugs maintain allograft function, suggesting that tolerance is already present. This strategy is feasible in 25-33% of liver transplant recipients. A series of experimental and clinical observations indicates that liver allografts can even provide "tolerogenic" properties for other organ grafts. In the clinical setting, clinical operational tolerance (COT) is defined as the absence of acute and chronic rejection and graft survival with normal function and histology in an IS-free, fully immunocompetent host, usually as an end result of a successful attempt at IS withdrawal. The exact mechanisms involved in achieving transplant tolerance remain unknown, although animal models suggest a possible role for regulatory T cells (Treg). Recent data have demonstrated an increase in the frequency of CD4+ CD25(high) T cells and FoxP3 transcripts during IS withdrawal in operationally tolerant liver transplant recipients. The data obtained from transcriptional profiling of the peripheral blood of IS-free liver transplant recipients suggest that there is a molecular signature of tolerance that could be employed to identify tolerant liver transplant recipients and that innate immune cells are likely to play a major role in the maintenance of COT after liver transplantation.


Assuntos
Tolerância Imunológica , Transplante de Fígado/imunologia , Animais , Apresentação de Antígeno , Biomarcadores , Bovinos , Células Dendríticas/classificação , Células Dendríticas/imunologia , Freemartinismo/imunologia , Perfilação da Expressão Gênica , Rejeição de Enxerto/genética , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/genética , Sobrevivência de Enxerto/imunologia , Humanos , Tolerância Imunológica/genética , Tolerância Imunológica/imunologia , Imunidade Inata , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Interleucinas/sangue , Camundongos , Especificidade de Órgãos , Seleção de Pacientes , Polimorfismo Genético , Ratos , Subpopulações de Linfócitos T/imunologia , Quimeras de Transplante/imunologia , Imunologia de Transplantes , Transplante Homólogo/imunologia
20.
Transplant Proc ; 53(9): 2659-2662, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34602295

RESUMO

BACKGROUND: Donation after circulatory death (DCD) is related to a warm ischemia time and more complications compared with traditional donors (donation after brain death [DBD]). METHODS: This study included biopsy samples retrospectively collected from November 2014 to December 2018 to compare histologic and biological markers of DCD and DBD liver grafts. The analysis includes marker of early apoptosis (p21), senescence (telomerase reverse transcriptase [TERT]), cell damage (caspase-3 active), endothelial damage (vascular endothelial growth factor), stem cell (CD90), hypoxia (HIF1A), inflammatory activation (COX-2), and cross-organ allograft rejection (CD44). A propensity score matching (PSM) was used to match patients receiving DCD livers to those receiving DBD livers. We analyzed the immunohistochemical initial liver damage-related warm ischemia time. RESULTS: Positive staining expression of liver damage biomarkers (COX-2, CD44, TERT, HIF1A, and CD90) was found, but no significant differences were found between DCD and DBD and with ischemic cholangiopathy. After PSM, there was a significant relationship between CD90 and male donors (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.07-0.91), TERT with donor sodium (OR, 1.11; 95% CI, 1.02-1.2), HIF1A with steatosis (OR, 0.33; 95% CI, 0.13-0.83), and CD44 with donor vasoactive drugs (OR, 0.36; 95% CI, 0.13-1) and glutamic oxaloacetic transaminase 1 week increase (OR, 1.01; 95% CI, 1-1.03). CONCLUSIONS: DCD immunohistochemical initial liver damage was found to behave similarly to DBD. The increase in complications and cholangiopathy associated with warm ischemia could be related to a different later phenomenon.


Assuntos
Morte Encefálica , Fator A de Crescimento do Endotélio Vascular , Biomarcadores , Sobrevivência de Enxerto , Humanos , Fígado , Masculino , Pontuação de Propensão , Estudos Retrospectivos
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