RESUMEN
To determine growth patterns in a large cohort of unselected children undergoing liver transplantation, the outcomes of 294 orthotopic liver transplantations performed in 221 children at The University of Chicago between October 1984 and October 1992 were retrospectively reviewed; 66% were alive at the time of this analysis. The mean age at transplantation was 4.1 +/- 5.0 years; 44% of the children were male and 16% of the transplants were from living-related donors. The mean height z score at the time of transplantation was -1.6 +/- 1.8, and 39% of children had height z scores of < -2.0 at transplantation. When children with growth retardation at the time of transplantation (height z scores of < -2. 0) were compared with children with more normal growth, there were no significant differences in gender or re-transplantation rates, although children with growth retardation at transplantation were significantly younger than those with more appropriate growth (2.8 +/- 4.1 years vs 4.7 +/- 5.1 years, P <.05). The height z score of all children with biliary atresia at the time of transplantation was -1.9 +/- 1.7 compared with -1.2 +/- 2.0 in those children with underlying diseases other than biliary atresia. Catch-up growth was seen in 37% to 47% of children at any given time point after transplantation. Children with evidence of catch-up growth (growth velocity z score >0) 2 years after transplantation were more likely to be first-time transplant recipients, had more growth retardation at the time of transplantation, and were receiving lower doses of prednisone at 2 years after transplantation. Younger children were most likely to demonstrate catch-up growth after transplantation. In summary, a large proportion of children have growth retardation at the time of liver transplantation. This growth retardation is inversely correlated with age. Before transplantation, children with biliary atresia grow less well than children with other forms of liver disease. Up to one half of children demonstrate catch-up growth after liver transplantation. Growth after transplantation is proportional to the degree of growth retardation at transplantation and inversely correlated to age at transplantation. Children with poor growth after transplantation are more likely to be receiving higher doses of corticosteroid.
Asunto(s)
Trastornos del Crecimiento/fisiopatología , Crecimiento/fisiología , Trasplante de Hígado , Estatura , Preescolar , Estudios de Cohortes , Femenino , Humanos , Terapia de Inmunosupresión , Inmunosupresores/uso terapéutico , Lactante , Masculino , Estudios Retrospectivos , Factores de TiempoRESUMEN
OBJECTIVE: Langerhans cell histiocytosis (LCH) is an unusual indication for orthotopic liver transplantation in children. Data from limited case reports suggest that orthotopic liver transplantation for LCH is associated with excellent survival rates and a low incidence of disease recurrence. However, in our experience, children who have transplantation for LCH appeared to experience a high incidence of refractory rejection and posttransplant lymphoproliferative disease (PTLD). STUDY DESIGN: Data from 398 liver transplants performed in 298 children younger than 16 years of age were reviewed to determine the presence of risk factors for PTLD in patients with LCH and other causes of liver failure. RESULTS: The incidence of PTLD was significantly higher in children who received transplants for LCH compared with all indications (p < 0.001) and specific indications that were associated with the development of PTLD (p < 0.002). Among patients in whom PTLD developed, there was no significant difference in the incidence of primary Epstein-Barr virus infections in patients who receive transplantation for LCH (4/4, 100%) versus all other indications (12/14, 86%). Children who had transplantation for LCH were older than those who had transplantation for other indications (LCH median age 3.1 years, other indications 1 year). The incidence of rejection, especially refractory rejection, was greater in patients who had transplantation for LCH (100% and 50%, respectively) compared with those who had transplantation for other indications (70% and 10%, p < 0.02 for refractory rejection). CONCLUSIONS: Patients who had transplantation for liver disease related to LCH experienced a 67% long-term survival (median follow up 5.8 years, range 2.1 to 7.5 years). Recurrent LCH occurred in only 33% of patients and was easily managed. However, PTLD developed in two thirds of these patients, perhaps in part because of the high incidence of refractory rejection. This series therefore demonstrates an association between a primary disease process and the development of PTLD. Although the data indicate that children with LCH-induced liver failure benefit from transplantation, special care must be exercised in screening for and preemptive treatment of PTLD.
Asunto(s)
Rechazo de Injerto/etiología , Histiocitosis de Células de Langerhans/cirugía , Trasplante de Hígado , Trastornos Linfoproliferativos/etiología , Adolescente , Factores de Edad , Antivirales/uso terapéutico , Azatioprina/uso terapéutico , Niño , Preescolar , Ciclosporina/uso terapéutico , Estudios de Seguimiento , Ganciclovir/uso terapéutico , Glucocorticoides/uso terapéutico , Infecciones por Herpesviridae/complicaciones , Herpesvirus Humano 4 , Histiocitosis de Células de Langerhans/complicaciones , Humanos , Inmunosupresores/uso terapéutico , Incidencia , Fallo Hepático/complicaciones , Fallo Hepático/cirugía , Trasplante de Hígado/efectos adversos , Metilprednisolona/uso terapéutico , Muromonab-CD3/uso terapéutico , Prednisona/uso terapéutico , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Tacrolimus/uso terapéutico , Infecciones Tumorales por Virus/complicacionesRESUMEN
OBJECTIVE: To describe fulminant hepatic failure (FHF) in children in the United States with clinical and histopathologic features distinctly different from those typical of FHF. PATIENTS: Seven young children were seen in early 1994 with encephalopathy, coagulopathy, and elevated aminotransferase levels. Liver failure was preceded by a prodromal viral illness that resulted in a period of fasting without dehydration. Unlike the majority of children with FHF, these patients had serum bilirubin levels < 171 mumol/L (10 mg/dl). All children had received therapeutic doses of acetaminophen during the prodromal illness. HISTOPATHOLOGIC FINDINGS: Histologic findings included zonal necrosis of hepatocytes in a centrilobular distribution, which is characteristic of toxic liver injury but is atypical for viral hepatitis and sporadic non-A non-B hepatitis. OUTCOME: Six patients recovered spontaneously, and one died of complications of liver failure and fungal sepsis. The cause of this disorder remains unknown, but we postulate a viral or environmental insult that preferentially damages zone 3 hepatocytes. The potential for this injury may have been augmented by ingestion of therapeutic doses of acetaminophen while patients were in a fasted state. The prognosis was good compared with typical FHF in children and correlated with the degree of liver necrosis on histologic examination.
Asunto(s)
Encefalopatía Hepática/diagnóstico , Hígado/patología , Acetaminofén/efectos adversos , Acetaminofén/sangre , Acetaminofén/uso terapéutico , Preescolar , Femenino , Fiebre/tratamiento farmacológico , Encefalopatía Hepática/sangre , Humanos , Lactante , Hígado/efectos de los fármacos , Masculino , Necrosis/etiología , Necrosis/patología , Índice de Severidad de la EnfermedadRESUMEN
Neonatal liver failure was evaluated in two infants. Neither infant had evidence of congenital infection, galactosemia, alpha 1-antitrypsin deficiency, tyrosinemia, Zellweger syndrome, or hemophagocytic lymphohistiocytosis. Abnormal levels of iron were detected in the minor salivary glands of the first infant and in the explanted liver of the second. Analyses of urinary bile salts by fast-atom bombardment ionization mass spectrometry and gas chromatography-mass spectrometry revealed a paucity of primary bile acids and a predominance of 7 alpha-hydroxy-3-oxo-4-cholenoic and 7 alpha,12 alpha-dihydroxy-3-oxo-4-cholenoic acids. These findings are consistent with delta 4-3-oxosteroid 5 beta-reductase deficiency, a primary genetic defect in bile acid synthesis. Postmortem evaluation of the first infant revealed significant iron deposition in the liver, pancreas, thyroid, adrenal glands, myocardium, stomach, and submucosal glands of the respiratory tract. In both infants examination of the liver revealed extensive loss of hepatic parenchyma. These cases expand the clinical spectrum of bile acid metabolism defects to include neonatal liver failure with associated hemochromatosis.
Asunto(s)
Hemocromatosis/etiología , Fallo Hepático/etiología , Oxidorreductasas/deficiencia , Ácidos y Sales Biliares/orina , Hemocromatosis/patología , Hemocromatosis/orina , Humanos , Lactante , Recién Nacido , Hígado/patología , Fallo Hepático/patología , Fallo Hepático/orina , MasculinoRESUMEN
The effect of primary measles vaccination after orthotopic liver transplantation was evaluated in 18 children. Immunity developed in seven children by serologic criteria. There were no complications directly attributable to the vaccine. These preliminary observations suggest that further study of measles vaccination in this group is warranted.
Asunto(s)
Trasplante de Hígado/inmunología , Vacuna Antisarampión/inmunología , Anticuerpos Antivirales/sangre , Preescolar , Femenino , Humanos , Inmunoglobulina G/sangre , Terapia de Inmunosupresión , Lactante , Masculino , Virus del Sarampión/inmunología , Periodo Posoperatorio , Factores de TiempoRESUMEN
To test the hypothesis that enhanced intestinal absorption of bilirubin may contribute to prolonged nonconjugated hyperbilirubinemia in human milk-fed infants, we studied a cross-section of 36 healthy infants and mothers. Milk from mothers and serum from infants were collected at 16.3 +/- 2.4 days. Milk was studied for its effect on the absorption of bilirubin labeled with carbon 14 in rats and compared with buffer and iron-fortified infant formula (Similac With Iron). The percentage of a 1 mg bilirubin dose absorbed by the rat was 25.29 +/- 4.0% when it was administered into the duodenum with buffer, 4.67 +/- 2.4% with Similac formula, and 7.7 +/- 2.9% with human milk. Linear regression analysis, using the infant's serum nonconjugated bilirubin level as the dependent variable and the percentage of (14C)bilirubin absorbed by the rat with the corresponding mother's milk as the independent variable, revealed a significant correlation (r = 0.40; p = 0.016). Inspection of the data suggested that absorptive permissiveness correlated closely with infant serum bilirubin values greater than 24 mumol/L (1.4 mg/dl) (r = 0.55; p = 0.007), whereas in those with bilirubin values less than or equal to 24 mumol/L, there was no apparent correlation. Milk was also analyzed for beta-glucuronidase, nonesterified fatty acids, and the ability to inhibit glucuronosyltransferase activity of rat liver microsomes in vitro, none of which correlated with the infant's serum bilirubin. These data support the theory that enhanced intestinal absorption of bilirubin contributes to the jaundice associated with breast-feeding.
Asunto(s)
Bilirrubina/farmacocinética , Duodeno/metabolismo , Absorción Intestinal , Leche Humana/metabolismo , Animales , Bilis/química , Bilirrubina/análisis , Bilirrubina/sangre , Radioisótopos de Carbono , Ácidos Grasos no Esterificados/análisis , Femenino , Glucuronidasa/antagonistas & inhibidores , Glucuronidasa/metabolismo , Humanos , Alimentos Infantiles , Recién Nacido , Masculino , Leche Humana/química , Leche Humana/enzimología , Ratas , Ratas EndogámicasRESUMEN
Fourteen infants requiring long-term total parenteral nutrition but able to tolerate small quantities of enteral feedings were randomized into carnitine treatment and placebo control groups. All infants had received nutritional support devoid of carnitine. Plasma carnitine levels and observed plasma lipid indices were not different before supplementation. Under standardized, steady-state conditions, 0.5 g/kg fat emulsion (intralipid) was administered intravenously over 2 hours both before and after infants received 7 days of continuous nasogastric or gastric tube L-carnitine (50 mumol/kg/day) or placebo. Plasma triglyceride, free fatty acid, acetoacetate, beta-hydroxybutyrate, and carnitine concentrations were observed at 0 (start of lipid infusion), 2, and 4 hours for pre- and post-treatment periods, and in addition at 6 and 8 hours after carnitine supplementation. Infants receiving carnitine had significantly greater beta-hydroxybutyrate plasma concentrations (P less than 0.05) and carnitine (P less than 0.001) at 0, 2, 4, 6, and 8 hours, and greater plasma acetoacetate concentrations (P less than 0.05) at 2, 4, 6, and 8 hours, compared with controls. Twenty-four-hour urinary carnitine excretion was very low for both groups before supplementation; after supplementation, excretion was higher (P less than 0.05) in the carnitine group. No significant differences were found between groups for plasma triglyceride or free fatty acid concentrations at any observation period. This study demonstrated enhanced fatty acid oxidation, as evidenced by increased ketogenesis, with L-carnitine supplementation in infants receiving long-term total parenteral nutrition.
Asunto(s)
Carnitina/administración & dosificación , Metabolismo de los Lípidos , Nutrición Parenteral Total , Ácido 3-Hidroxibutírico , Administración Oral , Carnitina/sangre , Carnitina/orina , Ensayos Clínicos como Asunto , Ácidos Grasos no Esterificados/sangre , Femenino , Humanos , Hidroxibutiratos/sangre , Lactante , Masculino , Distribución Aleatoria , Factores de Tiempo , Triglicéridos/sangreRESUMEN
A controlled, prospective comparison of the use of the infant seat versus prone, head-elevated positioning in a harness was undertaken in 15 infants with gastroesophageal reflux. pH monitoring of the distal esophagus demonstrated less reflux in the harness than in the seat (P less than 0.001) during 19 pairs of two-hour postprandial trials. This difference was the result of both fewer episodes (P less than 0.001) and briefer episodes (P less than 0.05). Prone-elevated positioning in the harness described is superior to positioning in an infant seat in the treatment of gastroesophageal reflux in infants younger than 6 months.
Asunto(s)
Reflujo Gastroesofágico/prevención & control , Postura , Unión Esofagogástrica/fisiopatología , Reflujo Gastroesofágico/fisiopatología , Humanos , Concentración de Iones de Hidrógeno , Lactante , Recién Nacido , Manometría , Estudios Prospectivos , Restricción Física/instrumentación , Factores de TiempoRESUMEN
Six infants are reported who developed an inflammatory proctocolitis in the first month of life while being breast fed exclusively. All has been born at term and had normal perinatal courses. None had growth failure or constitutional symptoms other than bloody diarrhea. No toxic, bacterial, viral, or parasitic cause was established. Rectal inflammation was suggested by the presence of fecal leukocytes and was confirmed by sigmoidoscopic observation of focal ulcerations, edema, and increased friability. Rectal biopsies demonstrated a wide spectrum of acute and chronic inflammatory changes. All infants responded clinically to initiation of feeding with either a hydrolyzed casein or a soy protein-based formula. Breast-feeding was subsequently resumed in five of the six infants; all experienced immediate recurrence of symptoms. Elimination of cow milk protein from the maternal diet led to tolerance of breast-feeding in two infants but there was no change in the other three. We believe that dietary protein-induced enterocolitis, previously reported in formula-fed infants, occurs occasionally in the exclusively breast-fed infant as well.
Asunto(s)
Lactancia Materna , Colitis/etiología , Proteínas en la Dieta/efectos adversos , Enfermedades del Recién Nacido/etiología , Colitis/patología , Dieta , Femenino , Humanos , Recién Nacido , Leche Humana , Recto/patologíaRESUMEN
Twenty-one infants who were candidates for TPN because of respiratory disease were randomized into experimental (TPN) and control (glucose-electrolyte) groups. Serum GOT, GPT, GGTP, 5' nucleotidase, total, direct, and conjugated (ethyl anthranilate-reactive) bilirubin, and bile salt concentrations were determined at entry into the study and at one week. One week of TPN caused significant elevations of GGTP, 5'-N and EA bilirubin values, whereas SGOT, SGPT, SBS, and total and direct bilirubin were unaffected. Addition of a lipid infusion to TPN did not alter these differences. These data are interpreted as showing: (1) amino acid infusion has an early effect on hepatic function which is independent of the many diseases for which this therapy is used and of the concomitant use of lipid; (2) the initial effect appears to be on the canalicular membrane; and (3) the sinusoidal membrane is apparently unaffected by one week of TPN.
Asunto(s)
Aminoácidos/efectos adversos , Hígado/efectos de los fármacos , Nutrición Parenteral Total/efectos adversos , Nutrición Parenteral/efectos adversos , Ácidos y Sales Biliares/análisis , Bilirrubina/análisis , Fluidoterapia , Humanos , Recién Nacido , Estudios Prospectivos , Distribución Aleatoria , Transaminasas/análisis , gamma-Glutamiltransferasa/análisisRESUMEN
The etiology of recurrent aspiration pneumonitis after the successful repair of esophageal atresia has not been defined. In order to explain this occurrence, we performed esophageal manometric examinations on eight patients who had undergone repair of EA and tracheoesophageal fistula. Two patients who had had recurrent pneumonia had subnormal pressure of the lower esophageal sphincter; they also had a history of severe regurgitation, and a barium esophagram demonstrated free gastroesophageal reflux. The LES incompetence in these patients was apparently corrected by administration of bethanechol.