British paediatric surveillance unit study of biliary atresia: outcome at 13 years.

BACKGROUND: Little information is available on contemporary, prospectively collected data on the long-term outcome of national cohorts of children with biliary atresia. OBJECTIVE: This study aimed to describe the current outcome of a national cohort of children with biliary atresia. PATIENTS AND METHODS: All 93 cases of biliary atresia in the United Kingdom and Ireland diagnosed between March 1993 and February 1995 were followed up prospectively. RESULTS: A total of 91 children underwent Kasai portoenterostomy in 15 individual centres. Only 2 centres treated more than 5 children annually. Median age at last follow-up was 12 years (range 0.25-14). Fifteen children (16%) have died: 10 after unsuccessful portoenterostomy, 1 of sepsis after successful portoenterostomy, and 4 after liver transplantation. Forty-two (45%) underwent liver transplantation at a median age of 1 year (range 0.5-9), with 90% survival. All 41 children with failed portoenterostomy (and 2 without portoenterostomy) died or underwent liver transplantation at a median age of 0.8 years (range 0.25-6.5). When the portoenterostomy was successful, 40 of 50 patients (80%) are alive without liver transplantation. The 13-year actuarial survival without liver transplantation is 43.8% overall and is better in children treated at centres that treat more than 5 cases yearly (54% vs 27.3%, P = 0.005). CONCLUSIONS: If the portoenterostomy is successful, then few children with biliary atresia will need transplantation before adolescence. Children with biliary atresia should be treated in experienced centres to maximize the chance of successful surgery.

Isoenzyme characterization in isolated elevation of alkaline phosphatase after liver transplantation in children.

BACKGROUND: Isolated transient elevation of alkaline phosphatase (ALP) in the absence of bone or liver disease has been reported in children including liver transplant patients. Specific isoenzyme patterns have been associated with this phenomenon in healthy children but have not been reported after liver transplantation. The discovery of the isoenzyme pattern associated with benign transient hyperphosphatasemia in one child prompted a study of all our posttransplant patients. METHODS: Retrospective analysis of ALP isoenzymes by polyacrylamide gel electrophoresis on banked serum samples. RESULTS: The incidence of isolated transient hyperphosphatasemia was 4.3%. All 11 children demonstrated the isoenzyme pattern associated with benign transient hyperphosphatasemia. In one child, the hyperphosphatasemia occurred on a background of chronic cholangiopathy and in a second, shortly after an episode of probable cytomegalovirus hepatitis. CONCLUSIONS: Isolated elevation of serum ALP after liver transplantation in children is common. Analysis of ALP isoenzymes, looking for the pattern of benign transient hyperphosphatasemia, can assist in the management of these children.

Diaphragmatic dysfunction after pediatric orthotopic liver transplantation.

BACKGROUND: Pediatric orthotopic liver transplantation (OLT) has a low mortality. Some children, however, have an adverse outcome defined as a prolonged ventilatory support requirement and protracted pediatric intensive care unit (PICU) stay. The aim of this study was to determine if that adverse outcome related to the child's condition pre-OLT and/or the development of a pleural effusion or diaphragmatic dysfunction. METHODS: The study included 210 children with a median age at transplantation of 45.5 months (range 0.2-252 months). Fourteen had undergone retransplantation. The duration of ventilatory support (intermittent positive pressure ventilation [IPPV]) and PICU admission and development of a pleural effusion and/or diaphragmatic dysfunction were documented for each child. The patients were divided into three groups according to whether they had acute liver failure (ALF), chronic liver disease at home (CHOM), or chronic liver failure sufficiently ill to be in the hospital awaiting transplantation (CHOSP). RESULTS: The 36 children with ALF were of similar age to the 138 CHOM and 36 CHOSP children but required longer IPPV (P<0.0001) and PICU stay (P<0.0001). Overall, 17 children developed diaphragmatic dysfunction and 138 pleural effusions; affected children required longer IPPV and PICU stay (P<0.01). Regression analysis demonstrated that diaphragmatic dysfunction, but not pleural effusion development, was associated with prolonged ventilation (P<0.01) and protracted PICU stay (P<0.05). Other risk factors were ALF (P<0.01), retransplantation (P<0.01), and young age (P<0.05). CONCLUSION: Diaphragmatic dysfunction adversely influences PICU morbidity after OLT. Early assessment of diaphragmatic function, and if necessary aggressive management, might improve outcome.

Bone mineral density and height gain in children with chronic cholestatic liver disease undergoing transplantation.

BACKGROUND: Osteodystrophy is a well-described complication of chronic liver disease. Previous reports in adults and children undergoing liver transplantation (LT) were discordant, with the former showing no improvement of bone disease in the first year after transplantation and the latter demonstrating remarkable benefit from it. Our aim was to perform a pilot study on osteodystrophy in children undergoing LT and evaluate the contribution of growth on bone mineral density (BMD) changes. METHODS: We studied six patients (two male), with a median age at transplantation of 8.8 (range 3.8-16.6) years. Indications for transplantation were biliary atresia and progressive familial intrahepatic cholestasis (three patients each). BMD was studied with dual-energy x-ray absorptiometry and biochemical markers of liver and bone function in patients before and at 3, 6, and 12 months after LT. RESULTS: Median L2-L4 spinal BMD was 0.54 g/cm2 (range 0.29-0.87) before LT, and 0.58 g/cm2 (0.27-0.86) at 3 months, 0.66 g/cm2 (0.36-1.00) at 6 months, and 0.76 g/cm2 (0.44-1.02) at 12 months after LT (P=0.005). Median height was 133 (range 93-167) cm before LT, and 134 (93-167) at 3 months, 136 (97-167) at 6 months, and 139 (102-167) at 12 months after LT. There was direct correlation between height gain and total body BMD improvement (r=0.929, P=0.007). CONCLUSION: BMD in children with chronic cholestatic liver disease improves remarkably by 12 months after LT. Catch-up growth in children can account for the different effect of LT on bone density between adult and pediatric populations in the first year after surgery.

Liver dysfunction induced by bile duct ligation and galactosamine injection alters cardiac protein synthesis.

Liver disease has been shown to affect the cardiovascular system and may influence cardiac protein metabolism. This hypothesis was tested by measuring rates of cardiac protein synthesis in 2 models of liver disease in rats. The study consisted of 5 groups--group 1: control, injected with saline and fed ad libitum; group 2: acute liver injury, by dosage with 400 mg/kg galactosamine; group 3: injected with saline and pair-fed to group 2; group 4: chronic liver disease, using bile duct ligation; and group 5: sham-operated and pair-fed to group 4. Rates of cardiac protein synthesis were measured using the flooding dose technique. After 1 week, galactosamine injection caused the following cardiac changes, i.e. group (2) versus (3): an increased RNA content, RNA/DNA ratio, and RNA/protein ratio. However, there was no change in DNA or protein content, or protein/DNA ratio. There was an increase in the fractional rate of protein synthesis, and the absolute synthesis rate. Cellular efficiency was increased, but RNA activity remained unchanged. Comparison of groups 4 and 5 showed that bile duct ligation caused no change in any parameters measured. Although comparison of the ad libitum-fed group 1 with the bile duct ligation group 4 showed reduced cardiac weight, protein, and RNA content, with decreased right ventricular absolute synthesis rates; this was also seen in the pair-fed group 5, suggesting that these effects were due solely to reduced oral intake. Thus, although galactosamine-induced acute liver injury caused marked changes in cardiac biochemistry, bile duct ligation per se did not. This study also illustrates the importance of including a pair-fed group.

Can energy expenditure be predicted in critically ill children?.

OBJECTIVE: To determine whether critically ill children are hypermetabolic and to calculate whether predictive equations are appropriate for critically ill children. DESIGN: Prospective, clinical study. SETTING: Pediatric intensive care unit. PATIENTS: A total of 57 children (39 boys) aged 9 months to 15.8 yrs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The median resting energy expenditure measurement measured by indirect calorimetry was 37.2 (range, 11.9-66.6) kcal x kg(-1) x day(-1). This was significantly lower than would be predicted using either the Schofield (42.7 [26.9-65.4] kcal x kg(-1) x day(-1)) or Fleisch equations (42.8 [20.9-66.2] kcalx kg(-1)-1 x day(-1), p < .001) but significantly higher than the White equation developed specifically for pediatric intensive care units (26.2 [8.5-70.1] kcal x kg(-1),day(-1), p < .0001). Methods comparison analysis showed the limits of agreement were -484 to 300, -461 to 319, and -3.2 to 854 kcal/day, respectively. Multivariate analysis indicated the following factors contribute to hypometabolism and hypermetabolism: age (p = .006), sex (p = .034), time spent in the pediatric intensive care unit (p = .001), diagnosis (p = .015), weight (p = .009), temperature (p = .04), continuous infusion for sedation (p = .04), and neuromuscular blockade (p = .03). CONCLUSION: Children do not become hypermetabolic during critical illness. These data suggest that agreement between resting energy expenditure and the predictive equations are so broad that they are inappropriate for use in critically ill children.

Neonatal herpes simplex virus infection presenting as acute liver failure: prevalent role of herpes simplex virus type I.

BACKGROUND: Acute liver failure (ALF) in neonates is rare but carries a high mortality without liver transplantation. Herpes simplex virus (HSV) is one of the microbes that more commonly causes ALF and is potentially treatable; hence, early diagnosis and treatment are important to avoid progression to liver failure. PATIENTS AND RESULTS: We have analysed retrospectively the case notes of 11 patients with HSV-induced ALF. A history of possible herpes infection was elicited in 5 parents, but HSV had not been suspected clinically. All patients were asymptomatic when discharged from postnatal units and were presented with nonspecific symptoms of poor feeding and lethargy within 2 weeks from birth. Seven of the 11 patients had HSV-1 infection, 4 HSV-2. Only 2 patients who received early treatment with intravenous acyclovir survived. CONCLUSIONS: HSV-related ALF in the neonatal period carries high morbidity and mortality and needs a high index of suspicion so that life-saving treatment can be started promptly. Both HSV-1 and HSV-2 can cause severe neonatal infection. It is important to recognise HSV infection in women of childbearing age and their sexual partners.

VPS33B mutation with ichthyosis, cholestasis, and renal dysfunction but without arthrogryposis: incomplete ARC syndrome phenotype.

Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome is a rare multisystem disorder first described in 1979 and recently ascribed to mutation in VPS33B, whose product acts in intracellular trafficking. Arthrogryposis, spillage of various substances in the urine, and conjugated hyperbilirubinemia define an ARC core phenotype, in some patients associated with ichthyosis, central nervous system malformation, deafness, and platelet abnormalities. We describe a patient with cholestasis, aminoaciduria, ichthyosis, partial callosal agenesis, and sensorineural deafness who, although homozygous for the novel VPS33B mutation 971delA/K324fs, predicted to abolish VPS33B function, did not exhibit arthrogryposis. The phenotypes associated with VPS33B mutation may include incomplete ARC.