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1.
Liver Int ; 40(8): 1972-1976, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32471013

RESUMO

Coronavirus disease 2019 (COVID-19) caused by a novel coronavirus called severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is driving a present day global pandemic. Immunosuppressed patients are regarded as a high-risk cohort. The following is a short report on COVID-19 in liver transplant recipients (n = 5) from a high volume UK liver transplant unit with a large follow-up cohort (n = 4500). Based on this limited data, liver transplant recipients appear to have a low incidence of COVID-19, with less severe symptoms than expected, when compared with the general population and other solid organ recipients. This possibly could be related to self-isolation adherence and/or the 'ideal' level of immunosuppression that favourably modulates the immune response to COVID-19.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Transplante de Fígado , Pneumonia Viral/epidemiologia , Adulto , COVID-19 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Prevalência , SARS-CoV-2
2.
Liver Transpl ; 23(3): 352-360, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28027602

RESUMO

The aim was to determine the factors associated with the use of delayed abdominal closure in pediatric liver transplantation (LT) and whether this affected outcome. From a prospectively maintained database, transplants performed in children (≤18 years) were identified (October 2010 to March 2015). Primary abdominal closure was defined as mass closure performed at time of transplant. Delayed abdominal closure was defined as mass closure not initially performed at the same time as transplant; 230 children underwent LT. Of these, 176 (76.5%) had primary closure. Age was similar between the primary and delayed groups (5.0 ± 4.9 versus 3.9 ± 5.0 years; P = 0.13). There was no difference in the graft-to-recipient weight ratio (GRWR) in the primary and delayed groups (3.4 ± 2.8 versus 4.1 ± 2.1; P = 0.12). Children with acute liver failure (ALF) were more likely to experience delayed closure then those with chronic liver disease (CLD; P < 0.001). GRWR was similar between the ALF and CLD (3.4 ± 2.4 versus 3.6 ± 2.7; P = 0.68). Primary closure children had a shorter hospital stay (P < 0.001), spent fewer days in pediatric intensive care unit (PICU; P = 0.001), and required a shorter duration of ventilation (P < 0.001). Vascular complications (arterial and venous) were similar (primary 8.2% versus delayed 5.6%; P = 0.52). Graft (P = 0.42) and child survival (P = 0.65) in the primary and delayed groups were similar. Considering timing of mass closure after transplant, patients in the early delayed closure group (<6 weeks) were found to experience a shorter time of ventilation (P = 0.03) and in PICU (P = 0.003). In conclusion, ALF was the main determinant of delayed abdominal closure rather than GRWR. The optimal time for delayed closure is within 6 weeks. The use of delayed abdominal closure does not adversely affect graft/child survival. Liver Transplantation 23 352-360 2017 AASLD.


Assuntos
Aloenxertos/anatomia & histologia , Sobrevivência de Enxerto , Falência Hepática Aguda/cirurgia , Transplante de Fígado/efeitos adversos , Fígado/anatomia & histologia , Complicações Pós-Operatórias/epidemiologia , Abdome , Fatores Etários , Peso Corporal , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Tempo de Internação , Falência Hepática Aguda/mortalidade , Masculino , Tamanho do Órgão , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Técnicas de Fechamento de Ferimentos
3.
Pediatr Transplant ; 20(4): 523-9, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27061278

RESUMO

Primary hyperoxaluria type 1 (PH1) is an inherited metabolic disease that culminates in ESRF. Pre-emptive liver transplantation (pLTx) treats the metabolic defect and avoids the need for kidney transplantation (KTx). An institutional experience of pediatric PH1 LTx is reported and compared to the literature. Between 2004 and 2015, eight children underwent pLTx for PH1. Three underwent pLTx with a median GFR of 40 (30-46) mL/min/1.73 m(2) and five underwent sequential combined liver-kidney transplantation (cLKTx); all were on RRT at the time of cLKTx. In one case of pLTx, KTx was required eight and a half yr later. pLTx was performed in older (median 8 vs. 2 yr) and larger children (median 27 vs. 7.75 kg) that had a milder PH1 phenotype. In pediatric PH1, pLTx, ideally, should be performed before renal and extrarenal systemic oxalosis complications have occurred, and pLTx can be used "early" or "late." Early is when renal function is preserved with the aim to avoid renal replacement. However, in late (GFR < 30 mL/min/1.73 m(2) ), the aim is to stabilize renal function and delay the need for KTx. Ultimately, transplant strategy depends on PH1 phenotype, disease stage, child size, and organ availability.


Assuntos
Hiperoxalúria Primária/cirurgia , Falência Renal Crônica/prevenção & controle , Transplante de Fígado , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Hiperoxalúria Primária/complicações , Lactente , Falência Renal Crônica/etiologia , Transplante de Rim , Masculino , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
4.
Liver Transpl ; 21(7): 914-21, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25907399

RESUMO

Early hepatic venous outflow obstruction (HVOO) can be a devastating complication leading to graft loss after liver transplantation (LT). A retrospective study on 777 adult LT recipients over a 5-year period (August 2007 to August 2012) was undertaken to determine the incidence of early HVOO presenting within 3 months of transplant, its clinical features and management, and potential technical risk factors related to the implanting technique. Cases of early HVOO were screened for by identifying recipients with problematic ascites within 3 months of transplant. Definitive diagnosis for HVOO was based on a wedge pressure of >12 mm Hg. Considering only whole livers, the incidence of early problematic ascites was 3% (20/695) of which more than one-third (35%, 7/20) were then confirmed to have HVOO. Overall, the incidence of early HVOO was 1% (7/695). Two hepatic veins (HVs) with extension piggybacks (PBs; n = 423) were the dominant implanting technique in the time period of study rather than the 3 HV PB (n = 182) and caval replacement techniques (n = 82). Considering the implantation technique, all cases of HVOO occurred after 2 HVs when extension PBs had been used with an incidence of 1.7% (7/423). Institutionally, early HVOO was mainly managed surgically by either cavoplasty within a month of transplant (n = 4) or retransplant (n = 1), and the remainder (n = 2) were medically managed with diuretics. In conclusion, early HVOO is rare, and there is no evidence from this study that a given implantation technique is at a higher risk of developing HVOO (2 HV with extension versus 3 HV and caval replacement; P = 0.11). However, early revisional surgery for HVOO can preserve graft function with retransplantation being reserved for when surgical cavoplasty or radiological stenting is technically not possible.


Assuntos
Síndrome de Budd-Chiari/diagnóstico , Síndrome de Budd-Chiari/terapia , Veias Hepáticas/cirurgia , Transplante de Fígado/métodos , Adulto , Idoso , Ascite/diagnóstico , Biópsia , Síndrome de Budd-Chiari/etiologia , Feminino , Sobrevivência de Enxerto , Humanos , Incidência , Fígado/irrigação sanguínea , Fígado/cirurgia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Resultado do Tratamento
5.
Pediatr Transplant ; 19(6): E139-41, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26103057

RESUMO

The following is the first report of a pediatric organ donor with caval agenesis and the subsequent use of this liver for transplantation. Caval embryology and potential implications of utilizing a donor liver with caval agenesis are reviewed.


Assuntos
Atresia Biliar/cirurgia , Transplante de Fígado , Doadores de Tecidos , Veia Cava Inferior/anormalidades , Feminino , Humanos , Lactente
6.
Liver Transpl ; 20(6): 698-704, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24604782

RESUMO

Donation after cardiac death (DCD) livers are considered to be marginal organs for solid organ and cell transplantation. Low energy charge (EC) and low purine quantity within the liver parenchyma has been associated with poor outcome after liver transplantation. The aim of this work was to assess the effect of anterograde persufflation (A-PSF) using an electrochemical concentrator on DCD liver energy status and hepatocyte function. Organs utilized for research were DCD livers considered not suitable for transplant. Each liver was formally split, and the control non-persufflated (non-PSF) section was stored in University of Wisconsin (UW) solution at 4°C. The A-PSF liver section was immersed in UW solution on ice, and A-PSF was performed via the portal vein with 40% oxygen. Tissue samples were taken 2 hours after A-PSF from the A-PSF and control non-PSF liver sections for snap freezing. Purine analysis was performed with photodiode array detection. Hepatocytes were isolated from A-PSF and control non-PSF liver sections using a standard organs utilized for research were DCD livers considered not suitable for transplant collagenase perfusion technique. Hepatocyte function was assessed using mitochondrial dehydrogenase activity {3-[4,5-dimethylthiazol-2-y1]-2,5-diphenyl tetrazolium bromide (MTT)} and the sulforhodamine B (SRB) assay for cell attachment. In DCD livers with <30% steatosis (n = 6), A-PSF increased EC from 0.197 ± 0.025 to 0.23 ± 0.035 (P = 0.04). In DCD livers with >30% steatosis (n = 4), A-PSF had no beneficial effect. After isolation (n=4, <30% steatosis), A-PSF was found to increase MTT from 0.92 ± 0.045 to 1.19 ± 0.55 (P < 0.001) and SRB from 2.53 ± 0.12 to 3.2 ± 0.95 (P < 0.001). In conclusion, A-PSF can improve the EC and function of isolated hepatocytes from DCD livers with <30% steatosis.


Assuntos
Metabolismo Energético , Fígado Gorduroso/metabolismo , Cardiopatias/mortalidade , Hepatócitos/efeitos dos fármacos , Preservação de Órgãos/métodos , Oxigênio/farmacologia , Perfusão/métodos , Doadores de Tecidos/provisão & distribuição , Adenosina/farmacologia , Idoso , Alopurinol/farmacologia , Temperatura Baixa , Seleção do Doador , Fígado Gorduroso/patologia , Gases , Glutationa/farmacologia , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Insulina/farmacologia , Pessoa de Meia-Idade , Soluções para Preservação de Órgãos/farmacologia , Purinas/metabolismo , Rafinose/farmacologia , Índice de Gravidade de Doença , Fatores de Tempo , Coleta de Tecidos e Órgãos
7.
Liver Transpl ; 20(12): 1429-35, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25124299

RESUMO

A diaphragmatic hernia (DH) is a rare complication of pediatric liver transplantation (LT), with multiple factors implicated in the pathophysiology. It is a potentially life-threatening condition in the absence of early recognition and surgical treatment. A DH after LT has been reported in 16 patients in 7 case series. We report 10 cases from our institution and review the published literature to understand the underlying pathophysiology. The study sample included all children (<18 years of age) who underwent LT from October 1989 to August 2013 at our center and subsequently presented with a DH. Among 4433 LT procedures performed in this time period, 1032 were for children. Ten DH cases were recognized, and risk factors were assessed. The mean age at diagnosis was 4.9 years, all patients with a DH received left lateral segment split grafts, and the mean graft weight was 248 ± 41 g with a mean graft-to-recipient body weight ratio (GBWR) of 3% ± 1.22% (range = 1.7%-5.0%). The mean cold ischemia time was 510.7 ± 307.6 minutes (range = 60-900 minutes). Six patients had a primary abdominal muscle closure, 3 had a temporary Silastic mesh closure, and 1 had a skin closure only. Postoperative ascites and pleural effusion did not appear to be significant risk factors. All 10 children presented with a right posterolateral DH, with 1 also having a left DH. The small bowel was herniated in the majority. All patients underwent prompt surgical intervention without complications. An early age, a split graft, and a high GBWR may be risk factors for a DH. A high index of suspicion and prompt surgical intervention minimize complications.


Assuntos
Hérnia Diafragmática/etiologia , Transplante de Fígado/efeitos adversos , Adolescente , Ascite/patologia , Peso Corporal , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Doadores Vivos , Masculino , Duração da Cirurgia , Complicações Pós-Operatórias/etiologia , Qualidade de Vida , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X , Resultado do Tratamento
8.
Front Bioeng Biotechnol ; 10: 1010824, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36237208

RESUMO

Background: Interest has revived in the use of hepatic arterial infusion chemotherapy (HAIC) for intermediate-advanced hepatocellular carcinoma (HCC) while transarterial chemoembolization (TACE) has been a longstanding loco-regional therapy. Aim: We conducted a systematic review and meta-analysis of patients with unresectable HCC treated with HAIC or TACE to look for differences in survival, adverse events, mortality and downstaging. Methods: All studies published before 29 July 2022 were identified by searching PubMed, Embase, Web of Science and Cochrane Library databases for patients with unresectable HCC and received HAIC or TACE as initial treatment. Data extracted from studies was statistically analysed using RevMan5.3 software. Results: A total of one randomized controlled trial (RCT) and 7 cohort studies (5 retrospective, 2 prospective) including 1,060 (TACE group: 534, HAIC group: 526) patients were screened. Compared with the TACE group, patients who received HAIC as initial therapy had better overall survival (OS) (HR = 0.53, 95%CI [0.40, 0.69]) and progression-free survival (PFS) (HR = 0.54, 95%CI [0.40, 0.72]). Further subgroup analysis revealed that HAIC showed priority over TACE on prognosis outcome regardless of tumour stage, especially in patients with advanced portal vein tumour thrombus (PVTT). Utilization of port system will not boost the efficacy of HAIC whereas using a replaced-microcatheter for each procedure could better reduce the progressive disease (PD) rate (RR = 0.55, 95%CI [0.40, 0.76]). The pooled RR favoured the HAIC group with regard to partial response (PR) (RR = 2.87, 95%CI [2.18, 3.78]) and this was validated by both GRADE summary and trial sequential analysis. The rate of resection after treatment was higher in the HAIC group (RR = 2.37, 95%CI [1.54, 3.66]), whilst no difference was found with procedure-related mortality (RR = 0.56, 95%CI [0.13, 2.38]) between two groups. Compared with the traditional chemotherapy regimen (fluorouracil/leucovorin/oxaliplatin) FOLFOX-HAIC appears to be better in improving the treatment efficacy. Conclusion: Patients with unresectable HCC could potentially benefit more from HAIC rather than standard TACE treatment. A re-evaluation of HAIC as a treatment option in intermediate and advanced HCC is warranted.

9.
Ann Surg ; 254(5): 716-22; discussion 722-3, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22042467

RESUMO

OBJECTIVE: To assess the incidence and impact of biliary complications in recipients transplanted from donors after cardiac death (DCD) at one single large institution. BACKGROUND: Shortage of available cadaveric organs is a significant limiting factor in liver transplantation (LT). The use of DCD offers the potential to increase the organ pool. However, early results with DCD liver grafts were associated with a greater incidence of ischemic cholangiopathy (IC), leading to several programs to abandoning this source of organs. METHODS: A retrospective analysis of a prospective database from April 2001 to 2010 focused on 167 consecutive DCD-LT. Each DCD transplant was matched with 2 brain death donors (DBD) grafts (n = 333) according to the period of transplantation. Primary outcome measures were biliary complications including the severity of complications, graft survival and patient survival. Minimum follow-up was 3 months. RESULTS: Anastomotic stricture was the most common biliary complication (DCD = 30, 19% vs. DBD = 41, 13%). Most were treated endocoscopically (grade IIIa = 72%), whereas hepatico-jejunostomy (grade IIIb) was performed in 22%. Primary IC occurred in 4 (2.5%) recipients from the DCD group and was absent in the DBD group (P = 0.005). However, none of these patients required retransplantation. Patient and graft survival at 1, 3, and 5 years were similar between DCD and DBD groups (P = 0.106, P = 0.138, P = 0.113, respectively). CONCLUSIONS: The encouraging results with DCD-LT are probably due to the selection of DCD grafts and clear definition of warm ischemia.


Assuntos
Doenças Biliares/epidemiologia , Transplante de Fígado , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , Pré-Escolar , Morte , Feminino , Sobrevivência de Enxerto , Humanos , Lactente , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Doadores de Tecidos , Adulto Jovem
10.
Cancer Res ; 81(22): 5765-5776, 2021 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-34551960

RESUMO

Cholangiocarcinoma is a form of hepatobiliary cancer with an abysmal prognosis. Despite advances in our understanding of cholangiocarcinoma pathophysiology and its genomic landscape, targeted therapies have not yet made a significant impact on its clinical management. The low response rates of targeted therapies in cholangiocarcinoma suggest that patient heterogeneity contributes to poor clinical outcome. Here we used mass spectrometry-based phosphoproteomics and computational methods to identify patient-specific drug targets in patient tumors and cholangiocarcinoma-derived cell lines. We analyzed 13 primary tumors of patients with cholangiocarcinoma with matched nonmalignant tissue and 7 different cholangiocarcinoma cell lines, leading to the identification and quantification of more than 13,000 phosphorylation sites. The phosphoproteomes of cholangiocarcinoma cell lines and patient tumors were significantly correlated. MEK1, KIT, ERK1/2, and several cyclin-dependent kinases were among the protein kinases most frequently showing increased activity in cholangiocarcinoma relative to nonmalignant tissue. Application of the Drug Ranking Using Machine Learning (DRUML) algorithm selected inhibitors of histone deacetylase (HDAC; belinostat and CAY10603) and PI3K pathway members as high-ranking therapies to use in primary cholangiocarcinoma. The accuracy of the computational drug rankings based on predicted responses was confirmed in cell-line models of cholangiocarcinoma. Together, this study uncovers frequently activated biochemical pathways in cholangiocarcinoma and provides a proof of concept for the application of computational methodology to rank drugs based on efficacy in individual patients. SIGNIFICANCE: Phosphoproteomic and computational analyses identify patient-specific drug targets in cholangiocarcinoma, supporting the potential of a machine learning method to predict personalized therapies.


Assuntos
Antineoplásicos/farmacologia , Colangiocarcinoma/metabolismo , Biologia Computacional/métodos , Fosfoproteínas/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Proteínas Quinases/química , Proteoma/metabolismo , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/metabolismo , Neoplasias dos Ductos Biliares/patologia , Biomarcadores Tumorais/antagonistas & inibidores , Biomarcadores Tumorais/metabolismo , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/patologia , Descoberta de Drogas , Humanos , Fosfoproteínas/análise , Fosfoproteínas/antagonistas & inibidores , Proteoma/análise , Células Tumorais Cultivadas
11.
Front Oncol ; 11: 738841, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34660300

RESUMO

INTRODUCTION: Hepatocellular carcinoma (HCC) is the most common primary liver cancer with a low 5-year survival rate. The heterogeneity of HCC makes monotherapy unlikely. The development of diagnostic programs and new treatments targeting common genetic events in the carcinogenic process are providing further insights into the management of HCC. The aim of this study was firstly to validate key genes that are involved in promoting HCC development and as biomarkers for early diagnosis and, secondly, to define their links with antitumor immunity including inhibitory checkpoints. METHODS: Multiple databases including Gene Expression Omnibus (GEO), Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier Plotter, UALCAN, and Oncomine were used for target gene screening and establishment of a co-expression network. Clinical data and RNAseq of 367 HCC patients were downloaded from the Cancer Genome Atlas (TCGA) database. The diagnostic and prognostic value of screened genes were tested by receiver operating characteristic (ROC) curve and correlation analysis. The links with the key genes in HCC and antitumor immunity were defined using both blood and liver tissue collected prospectively from HCC patients in our center. RESULTS: Upregulation of CCNB1, CDC20, and CENPF was commonly observed in HCC and are involved in the p53 signal pathway. The hepatic mRNA expression levels of these three genes were strongly associated with patients' prognosis and expressed high value of area under the ROC curve (AUC). Further analysis revealed that these three genes were positively correlated with the gene expression levels of IFN-γ, TNF-α, and IL-17 in peripheral blood. In addition, the expression of CENPF showed positive correlation with the percentage of CD8pos T cells and negative correlation with the percentage of CD4pos T cells in the peripheral blood. In the HCC microenvironment, the transcript levels of these three genes and inhibitory checkpoint molecules including PD-1, CTLA-4, and TIM-3 were positively correlated. CONCLUSION: The upregulation of CCNB1, CDC20, and CENPF genes was a common event in hepatocarcinogenesis. Expression levels of CCNB1, CDC20, and CENPF showed potential for early diagnosis and prediction of prognosis in HCC patients. There is a close association between three genes and Th1/Th17 cytokines as well as the count of CD4pos and CD8pos T cells. The positive correlation between the three genes and inhibitory checkpoint genes, PD-1, CTLA-4, and TIM-3, indicates that these genes are linked with weakened antitumor immunity in HCC. Our findings may provide further insights into developing novel therapies for HCC.

12.
Transplant Proc ; 53(10): 2939-2944, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34740449

RESUMO

BACKGROUND: Advancements based on artificial intelligence have emerged in all areas of medicine. Many decisions in organ transplantation can now potentially be addressed in a more precise manner with the aid of artificial intelligence. METHOD/RESULTS: All elements of liver transplantation consist of a set of input variables and a set of output variables. Artificial intelligence identifies relationships between the input variables; that is, how they select the data groups to train patterns and how they can predict the potential outcomes of the output variables. The most widely used classifiers to address the different aspects of liver transplantation are artificial neural networks, decision tree classifiers, random forest, and naïve Bayes classification models. Artificial intelligence applications are being evaluated in liver transplantation, especially in organ allocation, donor-recipient matching, survival prediction analysis, and transplant oncology. CONCLUSION: In the years to come, deep learning-based models will be used by liver transplant experts to support their decisions, especially in areas where securing equitability in the transplant process needs to be optimized.


Assuntos
Inteligência Artificial , Transplante de Fígado , Teorema de Bayes , Humanos , Redes Neurais de Computação , Doadores de Tecidos
15.
Sci Rep ; 8(1): 3105, 2018 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-29449571

RESUMO

Mitochondria have their own genomic, transcriptomic and proteomic machinery but are unable to be autonomous, needing both nuclear and mitochondrial genomes. The aim of this work was to use computational biology to explore the involvement of Mitochondrial microRNAs (MitomiRs) and their interactions with the mitochondrial proteome in a clinical model of primary non function (PNF) of the donor after cardiac death (DCD) liver. Archival array data on the differential expression of miRNA in DCD PNF was re-analyzed using a number of publically available computational algorithms. 10 MitomiRs were identified of importance in DCD PNF, 7 with predicted interaction of their seed sequence with the mitochondrial transcriptome that included both coding, and non coding areas of the hypervariability region 1 (HVR1) and control region. Considering miRNA regulation of the nuclear encoded mitochondrial proteome, 7 hypothetical small proteins were identified with homolog function that ranged from co-factor for formation of ATP Synthase, REDOX balance and an importin/exportin protein. In silico, unconventional seed interactions, both non canonical and alternative seed sites, appear to be of greater importance in MitomiR regulation of the mitochondrial genome. Additionally, a number of novel small proteins of relevance in transplantation have been identified which need further characterization.


Assuntos
Genoma Mitocondrial/genética , MicroRNAs/genética , Mitocôndrias/genética , Biologia Computacional/métodos , Simulação por Computador , Genômica/métodos , Humanos , Fígado/metabolismo , Transplante de Fígado/métodos , MicroRNAs/metabolismo , Mitocôndrias/metabolismo , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Proteoma/genética , Proteômica/métodos , Transcriptoma/genética
16.
Ann Transplant ; 22: 611-621, 2017 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-29026064

RESUMO

BACKGROUND This is the largest UK-based study on the effect of recipient body mass index (BMI) and its extremes (BMI <18.5 and BMI ≥35 kg/m²) on liver transplant (LT) outcomes. Its purpose was to analyze the BMI effect on post-LT mortality, graft loss, primary non-function (PNF), and graft vascular and biliary complications. MATERIAL AND METHODS Data were retrieved from a single-center LT database of 2,115 consecutive patients receiving first LT during period February 2004 to September 2015. Survivals were compared across the BMI groups; the effects of recipient BMI on survival, PNF, and graft vascular and biliary complications were analyzed via regression. RESULTS Autoimmune disease and nonalcoholic steatohepatitis were prevalent among underweight and morbidly obese adults, respectively. Graft survival was similar across BMI classes at 30 days and in 1, 2, 5, and 10 years (p=0.75) and on obese versus non-obese (p=0.33). BMI <35 kg/m² versus BMI ≥35 kg/m² mean graft survival was similar (p=0.84). BMI <18.5 kg/m² recipients tended to have inferior mean graft and patient survivals; however, the difference was non-significant (p=0.09 and p=0.1 respectively). BMI <18.5 kg/m² recipients were at higher risk of hepatic artery thrombosis (HR, 1.73, 95% CI 1.73-3, p<0.05). Adult underweight status was an independent HAT risk factor (HR 3, 95% CI 1-8.6, p=0.046). BMI class did not affect ischemic cholangiopathy risk (p=0.84). However, the overall biliary complication risk increased by 3% for every 1 kg/m² BMI rise. CONCLUSIONS Post-LT survival is independent of recipient BMI. Underweight status is linked to higher HAT risk. Biliary complication risk increases with rising recipient BMI. After appropriate recipient selection, recipient BMI extremes are not a contraindication for LT.


Assuntos
Índice de Massa Corporal , Doença Hepática Terminal/cirurgia , Sobrevivência de Enxerto/fisiologia , Transplante de Fígado/mortalidade , Transplantados , Adolescente , Adulto , Idoso , Criança , Doença Hepática Terminal/complicações , Feminino , Humanos , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/complicações , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Taxa de Sobrevida , Magreza/complicações , Resultado do Tratamento , Adulto Jovem
17.
World J Transplant ; 7(3): 203-212, 2017 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-28698837

RESUMO

AIM: To identify objective predictive factors for donor after cardiac death (DCD) graft loss and using those factors, develop a donor recipient stratification risk predictive model that could be used to calculate a DCD risk index (DCD-RI) to help in prospective decision making on organ use. METHODS: The model included objective data from a single institute DCD database (2005-2013, n = 261). Univariate survival analysis was followed by adjusted Cox-regressional hazard model. Covariates selected via univariate regression were added to the model via forward selection, significance level P = 0.3. The warm ischemic threshold was clinically set at 30 min. Points were given to each predictor in proportion to their hazard ratio. Using this model, the DCD-RI was calculated. The cohort was stratified to predict graft loss risk and respective graft survival calculated. RESULTS: DCD graft survival predictors were primary indication for transplant (P = 0.066), retransplantation (P = 0.176), MELD > 25 (P = 0.05), cold ischemia > 10 h (P = 0.292) and donor hepatectomy time > 60 min (P = 0.028). According to the calculated DCD-RI score three risk classes could be defined of low (DCD-RI < 1), standard (DCD-RI 2-4) and high risk (DCD-RI > 5) with a 5 years graft survival of 86%, 78% and 34%, respectively. CONCLUSION: The DCD-RI score independently predicted graft loss (P < 0.001) and the DCD-RI class predicted graft survival (P < 0.001).

18.
Artigo em Inglês | MEDLINE | ID: mdl-28138592

RESUMO

The introduction of liver transplant listing criteria for hepatocellular cancer (HCC) has significantly improved oncological outcomes and survival. But despite this HCC recurrence is still problematic. There is emerging evidence that the choice of immunosuppression (IS) after transplant for HCC can influence oncological survival and HCC recurrence. The following is a short summary of what has been published on HCC recurrence with the different classes of immunosuppressive agents in present use, concluding with the possible rationalization of the use of these immunosuppressive agents in the post-transplant patient at high risk of recurrence.

19.
Transplantation ; 100(9): 1916-24, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26982954

RESUMO

BACKGROUND: Hepatocellular cancer (HCC) is an established indication for liver transplantation. This group is often allocated a donor after cardiac death (DCD) liver as a solution for waiting times. There are concerns that this approach may oncologically disadvantage HCC recipients. The aim of this study was to determine whether DCD transplantation was associated with poorer cancer-related survival in HCC. METHODS: Study population was from a single institute (2001-2014) with an HCC listing diagnosis. Variables related to recipient, tumor, and graft were analyzed to determine association with HCC death. RESULTS: There were 347 recipients listed for HCC of which 91 received a DCD. Donor after cardiac death and donor after brain stem death (DBD) had equivalent 1-, 3-, and 5-year overall (P = 0.115) and cancer-specific survival (P = 0.7). On univariate analysis recipient age, sex, model for end stage liver disease, viral etiology had no bearing on the risk of HCC death. Neither did the graft variables of type (DCD vs DBD), donor age, steatosis, cold ischemic time, peak aspartate transaminase, day 5 bilirubin or international normalized ratio after transplant. Only tumor variables of alpha-fetoprotein, number, total diameter, microvascular invasion, and differentiation were predictors of HCC death. On multivariate analysis, predictors of HCC death remained tumor number (P = 0.002), total diameter of tumor(s) (P < 0.001), microvascular invasion (P = 0.025), and poor differentiation (P = 0.021). CONCLUSIONS: Donor liver quality in terms of graft type (DCD) has no influence on cancer related survival in transplant for HCC (hazards ratio, 1.143; 95% confidence interval, 0.528-2.423; P = 0.752).


Assuntos
Carcinoma Hepatocelular/cirurgia , Cardiopatias/mortalidade , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/métodos , Doadores de Tecidos/provisão & distribuição , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Causas de Morte , Diferenciação Celular , Distribuição de Qui-Quadrado , Bases de Dados Factuais , Seleção do Doador , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Londres , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral , Listas de Espera
20.
PLoS One ; 10(5): e0127073, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25978529

RESUMO

Donation after cardiac death (DCD) livers are marginal organs for transplant and their use is associated with a higher risk of primary non function (PNF) or early graft dysfunction (EGD). The aim was to determine if microRNA (miRNA) was able to discriminate between DCD livers of varying clinical outcome. DCD groups were categorized as PNF retransplanted within a week (n=7), good functional outcome (n=7) peak aspartate transaminase (AST) ≤ 1000 IU/L and EGD (n=9) peak AST ≥ 2500 IU/L. miRNA was extracted from archival formalin fixed post-perfusion tru-cut liver biopsies. High throughput expression analysis was performed using miRNA arrays. Bioinformatics for expression data analysis was performed and validated with real time quantitative PCR (RT-qPCR). The function of miRNA of interest was investigated using computational biology prediction algorithms. From the array analysis 16 miRNAs were identified as significantly different (p<0.05). On RT-qPCR miR-155 and miR-940 had the highest expression across all three DCD clinical groups. Only one miRNA, miR-22, was validated with marginal significance, to have differential expression between the three groups (p=0.049). From computational biology miR-22 was predicted to affect signalling pathways that impact protein turnover, metabolism and apoptosis/cell cycle. In conclusion, microRNA expression patterns have a low diagnostic potential clinically in discriminating DCD liver quality and outcome.


Assuntos
Fígado/metabolismo , MicroRNAs/genética , Transcriptoma/genética , Adulto , Aspartato Aminotransferases/sangue , Morte , Humanos , Transplante de Fígado/métodos , Pessoa de Meia-Idade , Doadores de Tecidos , Obtenção de Tecidos e Órgãos/métodos
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