RESUMO
BACKGROUND: As modern medicine is advancing, younger, small, and more complex children are becoming multi-organ transplant candidates. This brings up new challenges in all aspects of their care. METHODS: We describe the first report of a small child receiving a simultaneous liver and kidney transplant and abdominal rectus sheath fascia transplant on the background of Williams syndrome and methylmalonic acidaemia. At the time of transplantation, the child was 3 years old, weighed 14.0 kg, had chronic kidney disease stage V, and had not yet started any other form of kidney replacement therapy. RESULTS: There were many anaesthetic, medical, metabolic, and surgical challenges to consider in this case. A long general anaesthetic time increased the risk of cardiac complications and metabolic decompensation. Additionally, the small size of the patient and the organ size mis-match meant that primary abdominal closure was not possible. The patient's recovery was further complicated by sepsis, transient CNI toxicity, and de novo DSAs. CONCLUSIONS: Through a multidisciplinary approach between 9 specialties in 4 hospitals across England and Wales, and detailed pre-operative planning, a good outcome was achieved for this child. An hour by hour management protocol was drafted to facilitate transplant and included five domains: 1. management at the time of organ offer; 2. before the admission; 3. at admission and before theatre time; 4. intra-operative management; and 5. post-operative management in the first 24 h. Importantly, gaining a clear and in depth understanding of the metabolic state of the patient pre- and peri-operatively was crucial in avoiding metabolic decompensation. Furthermore, an abdominal rectus sheath fascia transplant was required to achieve abdominal closure, which to our knowledge, had never been done before for this indication. Using our experience of this complex case, as well as our experience in transplanting other children with MMA, and through a literature review, we propose a new perioperative management pathway for this complex cohort of transplant recipients.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos , Falência Renal Crônica , Transplante de Rim , Transplante de Fígado , Criança , Humanos , Pré-Escolar , Transplante de Fígado/efeitos adversos , Transplante de Fígado/métodos , Erros Inatos do Metabolismo dos Aminoácidos/complicações , Falência Renal Crônica/complicações , Fígado , Transplante de Rim/efeitos adversos , Transplante de Rim/métodosRESUMO
BACKGROUND: The Risk Estimation of Tumor Recurrence After Transplant (RETREAT) score as a prognostic index for recurrence has been reported previously and has not been validated outside the USA. Our study has validated the score in a single center UK cohort of patients being transplanted for HCC. METHODS: LT for HCC between 2008 and 2018 at our center were analyzed. Recurrence-free survival (RFS) was compared by the RETREAT score and validated using Net Reclassification Improvement (NRI) by comparing it to Milan criteria. RESULTS: 346 adult HCC patients were transplanted of whom 313 were included. 28 (8.9%) had a recurrence. Summation of largest diameter and total number of viable tumors (HR = 1.19, p < 0.001), micro-/macro-vascular invasion (HR = 3.74, p = 0.002) and AFP>20 ng/ml (HR = 3.03, p = 0.005) were associated with recurrence on multivariate analysis. RFS decreased with increasing RETREAT score (log-rank p = 0.016). RETREAT performed better than Milan with significant NRI at 1- and 2-years post-transplant (0.43 (p = 0.004) and 0.38 (p = 0.03) respectively). CONCLUSION: LT outcomes using the revised UK criteria are equivalent to Milan criteria. Further, RETREAT score was validated as a prognostic index for the first time in a UK cohort and may assist risk stratification, selection for adjuvant therapies and guide surveillance.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Adulto , Humanos , Transplante de Fígado/efeitos adversos , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Reino Unido , alfa-FetoproteínasRESUMO
BACKGROUND: Severe HPS increases morbidity and mortality after LT in children. We reviewed the combined experience of LT for HPS in children from two LT centers in Europe and Asia. METHODS: All children with "proven" HPS as per ERS Task Force criteria (detailed in manuscript) who underwent LT were categorized into M (PaO2 ≥80 mmHg), Mo (PaO2 = 60-79 mmHg), S (50-59 mmHg), and VS (PaO2 <50 mmHg) HPS, based on room air PaO2 . RESULTS: Twenty-four children with HPS underwent 25 LT (one re-transplantation) at a median age of 8 years (IQR, 5-12), after a median duration of 8 (4-12) months following HPS diagnosis. Mechanical ventilation was required for a median of 3 (1.5-27) days after LT. Ten children had "S" post-operative hypoxemia, requiring iNO for a median of 5 (6-27) days. "VS" category patients had significantly prolonged invasive ventilation (median 35 vs. 3 and 1.5 days; p = .008), ICU stay (median 39 vs. 8 and 8 days; p = .007), and hospital stay (64 vs. 26.5 and 23 days; p < .001) when compared to "S" and "M/Mo" groups, respectively. The need for pre-transplant home oxygen therapy was the only factor predicting need for re-intubation. Patient and graft survival at 32 (17-98) months were 100% and 95.8%. All children ultimately had complete resolution of HPS. CONCLUSIONS: VS HPS is associated with longer duration of mechanical ventilation and hospital stay, which emphasizes the need for early LT in these children.
Assuntos
Síndrome Hepatopulmonar/mortalidade , Síndrome Hepatopulmonar/cirurgia , Transplante de Fígado , Adolescente , Criança , Pré-Escolar , Feminino , Sobrevivência de Enxerto , Humanos , Lactente , Londres/epidemiologia , Masculino , Estudos Retrospectivos , Análise de SobrevidaRESUMO
Liver transplantation (LT) for patients with propionic acidemia (PA) is an emerging therapeutic option. We present a retrospective review of patients with PA who underwent LT at a tertiary liver center between 1995 and 2015. A total of 14 children were identified (8 males) with median age at initial presentation of 3 days (range, 0-77 days). Pretransplant median protein restriction was 1 g/kg/day (range, 0.63-1.75 g/kg/day), 71% required supportive feeding, and 86% had developmental delay. Frequent metabolic decompensations (MDs) were the main indication for LT with a median age at transplantation of 2.4 years (range, 0.8-7.1 years). Only 1 graft was from a living donor, and 13 were from deceased donors (4 auxiliary). The 2-year patient survival was 86%, and overall study and graft survival was 79% and 69%, respectively. Three patients died after LT: at 43 days (biliary peritonitis), 225 days (acute-on-chronic rejection with multiorgan failure), and 13.5 years (posttransplant lymphoproliferative disease). Plasma glycine and propionylcarnitine remained elevated but reduced after transplant. Of 11 survivors, 5 had at least 1 episode of acute cellular rejection, 2 sustained a metabolic stroke (with full recovery), and 3 developed mild cardiomyopathy after LT. All have liberalized protein intake, and 9 had no further MDs: median episodes before transplant, 4 (range, 1-30); and median episodes after transplant, 0 (range, 0-5). All survivors made some developmental progress after LT, and none worsened at a median follow-up of 5.8 years (range, 2-23 years). LT in PA significantly reduces the frequency of MDs, can liberalize protein intake and improve quality of life, and should continue to be considered in selected cases.
Assuntos
Transplante de Fígado , Acidemia Propiônica , Criança , Pré-Escolar , Humanos , Lactente , Transplante de Fígado/efeitos adversos , Doadores Vivos , Masculino , Acidemia Propiônica/diagnóstico , Acidemia Propiônica/cirurgia , Qualidade de Vida , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: We report our experience of treating anastomotic strictures using a novel type of fully covered metal stent (FCSEMS). This stent, known as the Kaffes Stent, is short-length with an antimigration waist and is easily removable due to long retrieval wires deployed within the duodenum. METHODS: Sixty-two patients underwent ERCP and Kaffes stent insertion for post-transplant anastomotic strictures following confirmation of a stricture on MRCP. These patients were retrospectively analysed for immediate and long-term stricture resolution, improvement in symptoms and liver function tests (LFTs), stricture recurrence and complication rates. RESULTS: Of the 56 patients who had their stent removed at the time of analysis, 54 (96%) had immediate stricture resolution and 42 continued to have long-term resolution (mean follow-up period was 548 days). Of the 16 patients with symptoms of biliary obstruction, 13 had resolution of their symptoms. Overall, there was a significant improvement in LFTs after stent removal compared to before stent insertion. Complication rates were 15% with only one patient requiring biliary reconstruction. CONCLUSIONS: The Kaffes stent is effective and safe at resolving post liver transplant biliary anastomotic strictures.
Assuntos
Transplante de Fígado , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Constrição Patológica/etiologia , Constrição Patológica/cirurgia , Humanos , Transplante de Fígado/efeitos adversos , Estudos Retrospectivos , Stents , Resultado do TratamentoRESUMO
Liver transplantation (LT) for small infants remains challenging because of the demands related to graft selection, surgical technique, and perioperative management. The aim of this study was to evaluate the short-term and longterm outcomes of LT regarding vascular/biliary complications, renal function, growth, and patient/graft survival in infants ≤3 months compared with those of an age between >3 and 6 months at a single transplant center. A total of 64 infants ≤6 months underwent LT and were divided into 2 groups according to age at LT: those of age ≤3 months (range, 6-118 days; XS group, n = 37) and those of age >3 to ≤6 months (range, 124-179 days; S group, n = 27) between 1989 and 2014. Acute liver failure was the main indication for LT in the XS group (n = 31, 84%) versus S (n = 7, 26%). The overall incidence of hepatic artery thrombosis and portal vein thrombosis/stricture were 5.4% and 10.8% in the XS group and 7.4% and 11.1% in the S group, respectively (not significant). The overall incidence of biliary stricture and leakage were 5.4% and 2.7% in the XS group and 3.7% and 3.7% in the S group, respectively (not significant). There was no significant difference between the 2 groups in terms of renal function. No significant difference was found between the 2 groups for each year after LT in terms of height and weight z score. The 1-, 5-, and 10-year patient survival rates were 70.3%, 70.3%, and 70.3% in the XS group compared with 92.6%, 88.9%, and 88.9% in the S group, respectively (not significant). In conclusion, LT for smaller infants has acceptable outcomes despite the challenges of surgical technique, including vascular reconstruction and graft preparation, and perioperative management.
Assuntos
Sobrevivência de Enxerto , Falência Hepática Aguda/cirurgia , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Fatores Etários , Feminino , Humanos , Incidência , Lactente , Falência Hepática Aguda/mortalidade , Masculino , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Primary abdominal wall closure after intestinal and multivisceral transplantation may not be possible because of loss of abdominal domain and/or graft size/abdominal cavity mismatch. Traditional closure techniques for the open abdomen may not be valid in these circumstances because of severe scarring of the abdominal wall from multiple previous surgeries in this particular group of patients. We present our initial experience with the use of non-vascularized abdominal rectus muscle fascia in two patients who underwent deceased donation and living-related combined liver and small bowel transplantation, respectively, and who could not be closed primarily. The donor fascia was attached to the recipient fascia in both patients. In either case, there was not enough skin cover for closure, the wound was left open, and a negative pressure dressing was applied. In both cases, over a period of 6 months after placement of the non-vascularized abdominal rectus muscle fascia, the wound contracted, granulation tissue gradually covered the wound, and healing occurred, giving an intact abdominal wall. The abdominal rectus muscle fascia from a deceased donor can be used in a definite procedure for closure of the abdominal wall either at the time of transplant or later when a suitable rectus muscle fascia graft becomes available.
Assuntos
Parede Abdominal/cirurgia , Fasciotomia , Intestinos/transplante , Técnicas de Fechamento de Ferimentos , Criança , Feminino , Humanos , MasculinoRESUMO
The following is a short report on the use of a heterozygous (PiMZ) alpha 1 antitrypsin (α1AT) living related donor liver in a homozygous (PiZ) child that was complicated by massive ascites early after transplant. This clinical report is then followed by a brief summary of present knowledge on the α1 AT protein and management of massive ascites in the pediatric liver transplant recipient.
Assuntos
Ascite/etiologia , Transplante de Fígado , Complicações Pós-Operatórias/etiologia , Deficiência de alfa 1-Antitripsina/complicações , Adulto , Ascite/diagnóstico , Evolução Fatal , Feminino , Heterozigoto , Homozigoto , Humanos , Lactente , Doadores Vivos , Complicações Pós-Operatórias/diagnóstico , Deficiência de alfa 1-Antitripsina/diagnóstico , Deficiência de alfa 1-Antitripsina/genéticaRESUMO
Citrullinemia or ASS deficiency in its classical form presents in the neonatal period with poor feeding, hyperammonemia, encephalopathy, seizures, and if untreated can be fatal. Despite advances in medical therapy, neurocognitive outcomes remain suboptimal. LT has emerged as a potential management option. A retrospective single-center review identified 7 children with a median age of 1.1 years (range, 0.6-5.8) at referral. Five children presented clinically, and 2 were treated prospectively from birth due to positive family history. All patients received standard medical and dietary therapy prior to LT. The indications for LT were frequent metabolic decompensations in 4, elective in 2, and ALF in 1. The median age at LT was 2.4 years (range, 1.3-6.5). Five patients received 6 left lateral segment grafts, one a live unrelated donor left lateral segment as an APOLT graft, and one a cadaveric whole liver graft as APOLT. One child required retransplantation due to hepatic artery thrombosis. Graft and patient survival were 86% and 100%, respectively. Median follow-up is 3.1 years (range, 0.1-4.1), and the median age at follow-up is 5.5 years (range, 4.0-9.8). There have been no metabolic decompensations in 6 children, while 1 patient (with APOLT) developed asymptomatic hyperammonemia with no clinical or histological signs of liver injury, requiring additional medical therapy. Our medium-term experience following LT in citrullinemia is favorable, demonstrating a positive transformation of the clinical phenotype.
Assuntos
Citrulinemia/cirurgia , Transplante de Fígado , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
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 FerimentosRESUMO
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 TratamentoRESUMO
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 TratamentoRESUMO
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 , LactenteAssuntos
Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Neoplasias Pancreáticas/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Cisplatino/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Terapia Neoadjuvante , Pancreatectomia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/secundárioRESUMO
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 TratamentoRESUMO
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 ÓrgãosRESUMO
The objective of this study was to identify peritransplant predictors of early graft survival and posttransplant parameters that could be used to predict early graft outcomes after pediatric liver transplantation (PLT). The response of children to liver dysfunction after liver transplantation (LT) is poor. No data have been reported for early predictors of poor graft survival, which would potentially be valuable for rescuing children at risk after LT. A retrospective cohort study of 422 PLT procedures performed from 2000 to 2010 at a single center was conducted. Multiple peritransplant variables were analyzed. Univariate and multivariate analyses using receiver operating characteristic curves were performed to identify predictors of early graft loss (ie, at 30, 60, and 90 days). The number needed to treat (NNT) was calculated when the risk factors were identified. Comparisons with the Olthoff criteria for early graft dysfunction in adults were performed. The overall 30-, 60-, and 90-day graft survival rates were 93.6%, 92.6%, and 90.7%, respectively. A recipient age of 0 to 2 or 6 to 16 years, acute liver failure, and a posttransplant day 7 serum bilirubin level > 200 µmol/L were risk factors for graft loss in the 3-strata Cox models. The product of the peak aspartate aminotransferase (AST) level, day 2 international normalized ratio (INR) value, and day 7 bilirubin level [with 30-, 60-, and 90-day areas under the receiver operating characteristic curve (AUROCs) of 0.774, 0.752, and 0.715, respectively] and a day 7 bilirubin level > 200 µmol/L (with 30-, 60-, and 90-day AUROCs of 0.754, 0.661, and 0.635, respectively) provided excellent prediction rates for early graft loss (30-days for Day-7-bilirubin level > 200) in the pediatric population (sensitivity = 72.7%, specificity = 96.6%, positive predictive value = 95.5%, negative predictive value = 78%). The NNT with early retransplantation when the day 7 bilirubin level was >200 µmol/L was 2.17 (unadjusted) or 2.76 (adjusted for graft survival). In conclusion, 2 scores-the product of the peak AST level, day 2 INR value, and day 7 bilirubin level and a posttransplant day 7 bilirubin level > 200 µmol/L-have been identified as clinically valuable tools with high accuracy for predicting early graft loss. A more aggressive attitude to considering early retransplantation in this group may further improve survival after LT.
Assuntos
Sobrevivência de Enxerto , Falência Hepática/terapia , Transplante de Fígado/métodos , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Análise Multivariada , Pediatria/métodos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Risco , Fatores de Tempo , Resultado do TratamentoAssuntos
Encefalopatia Hepática/terapia , Falência Hepática Aguda/cirurgia , Transplante de Fígado/métodos , Fígado/irrigação sanguínea , Derivação Portocava Cirúrgica/métodos , Acetaminofen/intoxicação , Adolescente , Adulto , Aloenxertos/irrigação sanguínea , Aloenxertos/diagnóstico por imagem , Aloenxertos/imunologia , Amônia/sangue , Analgésicos não Narcóticos/intoxicação , Biópsia , Feminino , Rejeição de Enxerto/prevenção & controle , Hepatectomia/métodos , Artéria Hepática/cirurgia , Encefalopatia Hepática/sangue , Encefalopatia Hepática/diagnóstico por imagem , Encefalopatia Hepática/etiologia , Humanos , Terapia de Imunossupressão/métodos , Imunossupressores/uso terapêutico , Fígado/diagnóstico por imagem , Fígado/patologia , Fígado/cirurgia , Falência Hepática Aguda/sangue , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/complicações , Veia Porta/diagnóstico por imagem , Veia Porta/cirurgia , Prednisolona/uso terapêutico , Tacrolimo/uso terapêutico , Tomografia Computadorizada por Raios X , Transplante Homólogo/métodos , Ultrassonografia Doppler , Veia Cava Inferior/diagnóstico por imagem , Veia Cava Inferior/cirurgiaAssuntos
Oxigenação por Membrana Extracorpórea/métodos , Transplante de Fígado/métodos , Adolescente , Anticoagulantes/administração & dosagem , Encefalopatias/cirurgia , Criança , Tomada de Decisões , Feminino , Rejeição de Enxerto , Hepatoblastoma/cirurgia , Humanos , Período Intraoperatório , Icterícia/cirurgia , Falência Hepática/cirurgia , Masculino , Recidiva , Estudos Retrospectivos , RiscoRESUMO
Bile flow restoration is a crucial step in the recovery process post transplantation of the liver. Here, metabolic trajectories based on changes in bile secretion - a known marker of functionality - have been utilised as an approach for discovering bile fluxes during transplantation. A total of ten liver transplants were monitored and from these 68 bile samples from both donors and recipients were collected and analysed using ultra-performance LC-MS in combination with multivariate statistical analysis. Based on the principal component scores constructed from the total bile fingerprint, differentiation of the bile acid concentrations before and after transplantation was detected. A trend was also observed, by constructing metabolic trajectories, whereby the post-transplant profiles approached the position of pre-transplant profiles within 30-60 min of the restoration of bile secretion function. The ten major conjugated bile acid salts were measured and a significant increase in concentrations of taurocholic acid and taurochenodeoxycholic acid were seen after transplantation. In addition, the ratios of secondary bile acids detected in gall bladder and hepatic bile were measured before and after transplantation. This study suggests that bile acid ratios in the donor liver at the pre-transplant and post-transplant stage may be important and that profiling of secreted bile after transplantation may aid clinical assessment and progress post-transplantation.