RESUMO
OBJECTIVES: To review recent evaluations of pediatric patients with intestinal failure (IF) for intestinal transplantation (ITx), waiting list decisions, and outcomes of patients listed and not listed for ITx at our center. METHODS: Retrospective chart review of 97 patients evaluated for ITx from January 2014 to December 2021 including data from referring institutions and protocol laboratory testing, body imaging, endoscopy, and liver biopsy in selected cases. Survival analysis used Kaplan-Meier estimates and Cox proportional hazards regression. RESULTS: Patients were referred almost entirely from outside institutions, one-third because of intestinal failure-associated liver disease (IFALD), two-thirds because of repeated infective and non-IFALD complications under minimally successful intestinal rehabilitation, and a single patient because of lost central vein access. The majority had short bowel syndrome (SBS). Waiting list placement was offered to 67 (69%) patients, 40 of whom for IFALD. The IFALD group was generally younger and more likely to have SBS, have received more parenteral nutrition, have demonstrated more evidence of chronic inflammation and have inferior kidney function compared to those offered ITx for non-IFALD complications and those not listed. ITx was performed in 53 patients. Superior postevaluation survival was independently associated with higher serum creatinine (hazard ratio [HR] 15.410, p = 014), whereas inferior postevaluation survival was associated with ITx (HR 0.515, p = 0.035) and higher serum fibrinogen (HR 0.994, p = 0.005). CONCLUSIONS: Despite recent improvements in IF management, IFALD remains a prominent reason for ITx referral. Complications of IF inherent to ITx candidacy influence postevaluation and post-ITx survival.
Assuntos
Intestinos , Listas de Espera , Humanos , Estudos Retrospectivos , Masculino , Feminino , Criança , Pré-Escolar , Lactente , Intestinos/transplante , Adolescente , Insuficiência Intestinal , Síndrome do Intestino Curto/cirurgia , Hepatopatias/cirurgiaRESUMO
Management of unresectable pediatric hepatoblastoma (HB) and hepatocellular carcinoma (HCC) remains challenging. The Society of Pediatric Liver Transplantation (SPLIT) database was used to study survival predictors in pediatric liver transplantation (LT) for HB and HCC. Event-free survival (EFS), associated risk factors, and postoperative complications were studied in children requiring LT for HB/HCC at 16 SPLIT centers. Three-year EFS was 81% for HB (n = 157) and 62% for HCC (n = 18) transplants. Of HB transplants, 6.9% were PRETEXT II and 15.3% were POST-TEXT I/II. Tumor extent did not impact survival (p = NS). Salvage (n = 13) and primary HB transplants had similar 3-year EFS (62% versus 78%, p = NS). Among HCC transplants, 3-year EFS was poorer in older patients (38% in ≥8-year-olds vs 86% <8-year-olds) and those with larger tumors (48% for those beyond versus 83% within Milan criteria, p = NS). Risk of infection (HR 1.5, 95% CI 1.1-2.2, p = .02) and renal injury (HR 2.4, 95% CI 1.7-3.3, p < .001) were higher in malignant versus nonmalignant LT. Survival is favorable for pediatric HB and HCC LT, including outcomes after salvage transplant. Unexpected numbers of LTs occurred in PRE/POST-TEXT I/II tumors. Judicious patient selection is critical to distinguish tumors that are potentially resectable; simultaneously, we must advocate for patients with unresectable malignancies to receive organs.
Assuntos
Carcinoma Hepatocelular , Hepatoblastoma , Neoplasias Hepáticas , Transplante de Fígado , Idoso , Carcinoma Hepatocelular/patologia , Criança , Hepatoblastoma/patologia , Hepatoblastoma/cirurgia , Humanos , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia , Estudos RetrospectivosRESUMO
BACKGROUND AND AIMS: Recurrent primary sclerosing cholangitis (rPSC) following liver transplant (LT) has a negative impact on graft and patient survival; little is known about risk factors for rPSC or disease course in children. APPROACH AND RESULTS: We retrospectively evaluated risk factors for rPSC in 140 children from the Pediatric PSC Consortium, a multicenter international registry. Recipients underwent LT for PSC and had >90 days of follow-up. The primary outcome, rPSC, was defined using Graziadei criteria. Median follow-up after LT was 3 years (interquartile range 1.1-6.1). rPSC occurred in 36 children, representing 10% and 27% of the subjects at 2 years and 5 years following LT, respectively. Subjects with rPSC were younger at LT (12.9 vs. 16.2 years), had faster progression from PSC diagnosis to LT (2.5 vs. 4.1 years), and had higher alanine aminotransferase (112 vs. 66 IU/L) at LT (all P < 0.01). Inflammatory bowel disease was more prevalent in the rPSC group (86% vs. 66%; P = 0.025). After LT, rPSC subjects had more episodes of biopsy-proved acute rejection (mean 3 vs. 1; P < 0.001), and higher prevalence of steroid-refractory rejection (41% vs. 20%; P = 0.04). In those with rPSC, 43% developed complications of portal hypertension, were relisted for LT, or died within 2 years of the diagnosis. Mortality was higher in the rPSC group (11.1% vs. 2.9%; P = 0.05). CONCLUSIONS: The incidence of rPSC in this cohort was higher than previously reported, and was associated with increased morbidity and mortality. Patients with rPSC appeared to have a more aggressive, immune-reactive phenotype. These findings underscore the need to understand the immune mechanisms of rPSC, to lay the foundation for developing new therapies and improve outcomes in this challenging population.
Assuntos
Colangite Esclerosante/cirurgia , Rejeição de Enxerto/epidemiologia , Hipertensão Portal/epidemiologia , Transplante de Fígado , Adolescente , Fatores Etários , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Criança , Colangite Esclerosante/sangue , Colangite Esclerosante/epidemiologia , Progressão da Doença , Resistência a Medicamentos , Feminino , Glucocorticoides/uso terapêutico , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto , Humanos , Hipertensão Portal/fisiopatologia , Doenças Inflamatórias Intestinais/epidemiologia , Internacionalidade , Masculino , Recidiva , Sistema de Registros , Fatores de Risco , Fatores de Tempo , gama-Glutamiltransferase/sangueRESUMO
BACKGROUND: Variation in IS exists among pediatric liver transplant centers. While individual centers may publish their practice paradigms, current data on practices as a whole are lacking. This study sought to ascertain the IS protocols of pediatric liver transplant centers within the SPLIT to better understand variability and similarities among peer institutions. METHODS: A 27-item questionnaire was developed within the SPLIT Quality Improvement and Clinical Care Committee. The survey collected data regarding center demographics, IS practices, and treatment of acute cellular rejection. RESULTS: Twenty-eight (64%) SPLIT centers responded with 22 (79%) centers performing more than 10 transplants per year and 17 (61%) following more than 100 post-transplant recipients. All centers use a written protocol, and 25 (89%) have a dedicated transplant pharmacist/PharmD. Twenty-five (89%) centers use steroids for induction alone or in combination with thymoglobulin/interleukin-2 antibodies. All centers use tacrolimus for initial maintenance therapy. Most centers have specialized protocols for ABO-incompatible transplants, recipients with renal dysfunction, autoimmune liver diseases, and liver tumors. Treatment of rejection varied but was associated with escalation in IS. CONCLUSION: IS practices among pediatric liver transplant centers are similar including the use of written protocols, pharmacy involvement, steroids for induction, tacrolimus as initial IS, tacrolimus reduction/delay for renal dysfunction, and escalation of IS with rejection severity. However, other IS practices show wide variability including treatment for ABO-incompatible grafts and presumed rejection. This study serves as a foundation to guide prospective research linking IS practice to outcomes to determine best practice.
Assuntos
Rejeição de Enxerto/prevenção & controle , Disparidades em Assistência à Saúde/estatística & dados numéricos , Terapia de Imunossupressão/métodos , Imunossupressores/uso terapêutico , Transplante de Fígado , Padrões de Prática Médica/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Quimioterapia Combinada , Rejeição de Enxerto/terapia , Pesquisas sobre Atenção à Saúde , Humanos , Terapia de Imunossupressão/normas , Terapia de Imunossupressão/estatística & dados numéricos , Quimioterapia de Indução/métodos , Quimioterapia de Indução/normas , Quimioterapia de Indução/estatística & dados numéricos , Lactente , Recém-Nascido , Quimioterapia de Manutenção/métodos , Quimioterapia de Manutenção/normas , Quimioterapia de Manutenção/estatística & dados numéricos , Padrões de Prática Médica/normas , Melhoria de Qualidade , Sociedades Médicas , Estados UnidosRESUMO
OBJECTIVE: To determine the association among nonalcoholic fatty liver disease (NAFLD), metabolic function, and cardiac function in obese adolescents. STUDY DESIGN: Intrahepatic triglyceride (IHTG) content (magnetic resonance spectroscopy), insulin sensitivity and ß-cell function (5-hour oral glucose tolerance test with mathematical modeling), and left ventricular function (speckle tracking echocardiography) were determined in 3 groups of age, sex, and Tanner matched adolescents: (1) lean (n=14, body mass index [BMI]=20±2 kg/m2); (2) obese with normal (2.5%) IHTG content (n=15, BMI=35±3 kg/m2); and (3) obese with increased (8.7%) IHTG content (n=15, BMI=37±6 kg/m2). RESULTS: The disposition index (ß-cell function) and insulin sensitivity index were â¼45% and â¼70% lower, respectively, and whole body insulin resistance, calculated by homeostasis model of assessment-insulin resistance (HOMA-IR), was â¼60% greater, in obese than in lean subjects, and â¼30% and â¼50% lower and â¼150% greater, respectively, in obese subjects with NAFLD than those without NAFLD (P<.05 for all). Left ventricular global longitudinal systolic strain and early diastolic strain rates were significantly decreased in obese than in lean subjects, and in obese subjects with NAFLD than those without NAFLD (P<.05 for all), and were independently associated with HOMA-IR (ß=0.634). IHTG content was the only significant independent determinant of insulin sensitivity index (ß=-0.770), disposition index (ß=-0.651), and HOMA-IR (ß=0.738). CONCLUSIONS: These findings demonstrate that the presence of NAFLD in otherwise asymptomatic obese adolescents is an early marker of cardiac dysfunction.
Assuntos
Fígado Gorduroso/fisiopatologia , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Fígado/fisiopatologia , Obesidade/complicações , Adolescente , Índice de Massa Corporal , Estudos Transversais , Fígado Gorduroso/metabolismo , Feminino , Humanos , Resistência à Insulina , Fígado/metabolismo , Espectroscopia de Ressonância Magnética , Masculino , Hepatopatia Gordurosa não Alcoólica , Obesidade/metabolismo , Obesidade/fisiopatologia , Triglicerídeos/metabolismoRESUMO
Neonatal acute liver failure (NALF) is a rare disease with a few known primary causes: gestational alloimmune liver disease (GALD), viral infections, metabolic diseases, and ischemic injury. Many cases still do not have a known cause. Laboratory evaluation may suggest a diagnosis. Most of the known causes have disease-specific treatments that improve outcomes. Survival is improving with better knowledge about and treatment options for GALD; however, overall mortality for NALF is still 24%. Liver transplant remains an important option for neonates with an indeterminate cause of NALF and those who do not respond to established treatments.
Assuntos
Falência Hepática Aguda/congênito , Doenças Raras/congênito , Humanos , Recém-Nascido , Falência Hepática Aguda/etiologia , Falência Hepática Aguda/mortalidade , Falência Hepática Aguda/terapia , Triagem Neonatal , Prognóstico , Doenças Raras/etiologia , Doenças Raras/mortalidade , Doenças Raras/terapiaRESUMO
INTRODUCTION: Biliary complications after pediatric orthotopic liver transplantation remain causes of significant patient morbidity. Staged operative approach in complex hepatobiliary surgery has improved postoperative outcomes but has not been evaluated in pediatric orthotopic liver transplantation. We sought to analyze the outcomes of staged biliary reconstruction after orthotopic liver transplantation in high acuity patients. METHODS: A retrospective analysis of 43 pediatric orthotopic liver transplantations at our center (January 2013 through December 2017). Median follow-up was 25 months. Variables were compared for group I: 1-stage orthotopic liver transplantation with biliary anastomosis (nâ¯=â¯6) versus group II: staged biliary reconstruction orthotopic liver transplantation (nâ¯=â¯37). RESULTS: Comparing groups I and II, median age (7.3 vs 4.8 years), weight (27 vs 19 kg), proportion of urgent orthotopic liver transplantation (50% vs 65%), partial graft orthotopic liver transplantation (33% vs 35%), and intraoperative red blood cell transfusion volume (11 vs 21 mL/kg) were comparable. Roux-en-Y hepaticojejunostomy was performed in 67% (group I) and 49% (group II). There was no biliary complication in both groups. For groups I and II, 3-year survival rates for graft (100% vs 92%, Pâ¯=â¯.477) and patient (100% vs 97%, Pâ¯=â¯.679) were comparable. CONCLUSION: Our study showed excellent outcomes with staged biliary reconstruction orthotopic liver transplantation in high acuity pediatric transplant recipients. This is the first report showing clinical applicability of staged biliary reconstruction orthotopic liver transplantation in children.
Assuntos
Anastomose em-Y de Roux , Ductos Biliares/cirurgia , Coledocostomia , Jejunostomia , Transplante de Fígado , Temperatura Corporal , Criança , Pré-Escolar , Transfusão de Eritrócitos , Feminino , Sobrevivência de Enxerto , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Estudos Retrospectivos , StentsRESUMO
Among infants, almost half of acute liver failure cases are classified as indeterminate, whereas only a small number of cases show a documented viral infection. We present the first reported case of isolated acute hepatic failure in an infant in the setting of a human parechovirus (HPeV) infection. HPeV also may have been contributory to the posttransplant complication of 2 intussusceptions. This is a 10-month-old girl who presented with only symptoms of fussiness and was noted to have progressive decline in synthetic liver function as well as worsening coagulopathy requiring a liver transplant. The acute liver failure was in the setting of a positive serum RNA HPeV, subtype 3 (HPeV-3), after extensive diagnostic testing with genetic, autoimmune, and infectious causes otherwise negative. After liver transplantation, the postoperative course was complicated by both an ileal-ileal intussusception as well as a jejunal intussusception. Viral testing in pediatric acute liver failure is often performed, but the workup is frequently incomplete. This case report would support more extensive viral testing in this population of patients. In the setting of HPeV, clinicians could be alerted to the possibility of delayed gastrointestinal pathology in the posttransplant phase. Wider use of routine HPeV testing may more clearly define the variable clinical presentations and outcomes.
Assuntos
Falência Hepática Aguda/virologia , Infecções por Picornaviridae/complicações , Feminino , Humanos , Doenças do Íleo/etiologia , Doenças do Íleo/cirurgia , Lactente , Intussuscepção/etiologia , Intussuscepção/cirurgia , Doenças do Jejuno/etiologia , Doenças do Jejuno/cirurgia , Falência Hepática Aguda/cirurgia , Transplante de Fígado , Parechovirus/isolamento & purificação , Infecções por Picornaviridae/diagnóstico , Complicações Pós-Operatórias , RNA Viral/sangueRESUMO
OBJECTIVE: It has been hypothesized that excessive fatty acid availability contributes to steatosis and the metabolic abnormalities associated with nonalcoholic fatty liver disease (NAFLD). The purpose of this study was to evaluate whether adipose tissue lipolytic activity and the rate of fatty acid release into plasma are increased in obese adolescents with NAFLD. METHODS: Palmitate kinetics were determined in obese adolescents with normal (n = 9; BMI = 37 +/- 2 kg/m(2); intrahepatic triglyceride (IHTG)
Assuntos
Fígado/metabolismo , Obesidade/metabolismo , Ácido Palmítico/metabolismo , Triglicerídeos/metabolismo , Abdome , Tecido Adiposo/anatomia & histologia , Adolescente , Composição Corporal , Índice de Massa Corporal , Fígado Gorduroso/metabolismo , Feminino , Técnica Clamp de Glucose , Humanos , Hiperinsulinismo , Imageamento por Ressonância Magnética , Masculino , Ácido Palmítico/sangue , PeleRESUMO
Obesity in adolescents is associated with metabolic risk factors for type 2 diabetes, particularly insulin resistance and excessive accumulation of intrahepatic triglyceride (IHTG). The purpose of this study was to evaluate the effect of moderate weight loss on IHTG content and insulin sensitivity in obese adolescents who had normal oral glucose tolerance. Insulin sensitivity, assessed by using the hyperinsulinemic-euglycemic clamp technique in conjunction with stable isotopically labeled tracer infusion, and IHTG content, assessed by using magnetic resonance spectroscopy, were evaluated in eight obese adolescents (BMI >or=95th percentile for age and sex; age 15.3 +/- 0.6 years) before and after moderate diet-induced weight loss (8.2 +/- 2.0% of initial body weight). Weight loss caused a 61.6 +/- 8.5% decrease in IHTG content (P = 0.01), and improved both hepatic (56 +/- 18% increase in hepatic insulin sensitivity index, P = 0.01) and skeletal muscle (97 +/- 45% increase in insulin-mediated glucose disposal, P = 0.01) insulin sensitivity. Moderate diet-induced weight loss decreases IHTG content and improves insulin sensitivity in the liver and skeletal muscle in obese adolescents who have normal glucose tolerance. These results support the benefits of weight loss therapy in obese adolescents who do not have evidence of obesity-related metabolic complications during a standard medical evaluation.
Assuntos
Comportamento do Adolescente , Terapia Comportamental , Resistência à Insulina , Fígado/metabolismo , Músculo Esquelético/metabolismo , Obesidade/terapia , Comportamento de Redução do Risco , Redução de Peso , Adolescente , Glicemia/metabolismo , Ingestão de Energia , Exercício Físico , Feminino , Técnica Clamp de Glucose , Teste de Tolerância a Glucose , Humanos , Insulina/metabolismo , Cinética , Fígado/fisiopatologia , Espectroscopia de Ressonância Magnética , Masculino , Músculo Esquelético/fisiopatologia , Obesidade/metabolismo , Obesidade/fisiopatologia , Resultado do Tratamento , Triglicerídeos/metabolismoRESUMO
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) and insulin resistance are common in overweight adolescents. OBJECTIVE: The purpose of this study was to determine the relation between NAFLD and insulin sensitivity in liver and skeletal muscle by studying overweight adolescents with a normal or high intrahepatic triglyceride (IHTG) content, who were matched for age, sex, body mass index (BMI; in kg/m(2)), and Tanner stage. DESIGN: Stable-isotope-labeled tracer infusion and the hyperinsulinemic-euglycemic clamp procedure were used to assess skeletal muscle and hepatic insulin sensitivity, and magnetic resonance spectroscopy was used to assess the IHTG content in 10 overweight (BMI = 35.9 +/- 1.3) adolescents with NAFLD (IHTG = 28.4 +/- 3.4%) and 10 overweight (BMI = 36.6 +/- 1.5) adolescents with a normal IHTG content (3.3 +/- 0.5%). RESULTS: The baseline plasma glucose concentration and the rate of appearance of glucose in plasma were the same in subjects with a normal (87.1 +/- 1.2 mg/dL, 16.2 +/- 1.1 micromol . kg fat-free mass(-1) . min(-1)) or high (89.2 +/- 2.5 mg/dL, 16.3 +/- 1.2 micromol . kg fat-free mass(-1) . min(-1)) IHTG content. However, compared with subjects who had a normal IHTG content, subjects with NAFLD had a lower hepatic insulin sensitivity index, based on baseline glucose kinetics and insulin concentrations (4.0 +/- 0.5 compared with 2.4 +/- 0.4; P < 0.05) and an impaired increase in glucose uptake during insulin infusion (169 +/- 28.1% compared with 67 +/- 9.6% above baseline; P < 0.01). In addition, the plasma triglyceride concentration was greater and the plasma HDL-cholesterol concentration was lower in subjects with NAFLD than in those with a normal IHTG content. CONCLUSION: An elevated IHTG content in overweight adolescents is associated with dyslipidemia and with insulin-resistant glucose metabolism in both liver and skeletal muscle.