Faecal elastase 1 levels in premature and full term infants.

BACKGROUND: Determination of faecal elastase 1 (FE1) is a simple, relatively inexpensive, non-invasive, highly specific and sensitive test for determining pancreatic function. Secretion of pancreatic enzymes varies during infancy, but there are almost no specific data on the ontogeny of elastase 1 in human babies. AIM: To study FE1 levels in preterm and term babies, and to determine the possible effect of gestational and postconceptual age on these levels. METHODS: Serial stool samples were collected and tested for FE1 level from 77 premature and full term infants. FE1 levels were determined by a commercially available enzyme linked immunosorbent assay (ELISA) kit. RESULTS: A total of 232 stool samples were collected from 77 neonates. The FE1 level measured in the first stool sample (meconium) was below normal (200 micro g/g stool) in all samples regardless of gestational age. Sixty three neonates had at least two samples tested for FE1 level. The mean (SD) level of FE1 in sample 1 was 45.9 (51.1) micro g/g stool and was significantly (p < 0.001) lower than in sample 2 (243.0 (164.9) micro g/g stool). The lower the gestational age of the newborn, the more time it took for FE1 to reach normal levels. CONCLUSIONS: FE1 levels in meconium are low, and studies in meconium should be avoided if pancreatic sufficiency is to be determined. FE1 reaches normal levels by day 3 in term newborns and by 2 weeks in infants born before 28 weeks gestation. Normal levels are reached sooner in infants of more advanced gestational age who start enteral feeding earlier.

Primary hyperoxaluria type 1: improved outcome with timely liver transplantation: a single-center report of 36 children.

BACKGROUND: The appropriate use of liver transplantation in children with type-1 primary hyperoxaluria (PH-1) is not well established. We reviewed our experience with 36 children with PH-1, including 12 who underwent liver transplantation. PATIENTS AND METHODS: From 1989-1998, 36 children from 10 families in northern Israel were diagnosed with PH-1. Eight children presented with renal failure; seven of these eight had the severe infantile form of the disease. One child was treated with kidney transplantation alone. Combined liver-kidney transplantation has been performed in nine children and preemptive liver transplantation in three children. A review of the patients' charts for the following parameters was performed: age, clinical signs, and renal sonographic findings at diagnosis, age at onset of dialysis, and current status. Type of transplant, pre- and posttransplant urine oxalate excretion, current renal function, survival, and complications were recorded in liver recipients. RESULTS: Of the 23 nontransplanted children, 9 died of complications related to severe systemic oxalosis and 14 are alive (mean follow-up, 7.4 years), including 2 who are candidates for transplantation. The child who underwent only kidney transplantation died of unrelated causes. Of the 12 liver recipients, 2 died within the first 3 months posttransplant and another child underwent retransplantation due to hepatic arterial thrombosis. At intervals after transplant ranging from 6-54 months, 10 recipients are alive (7 of the 9 recipients of combined liver-kidney transplants and all 3 recipients of preemptive liver transplants). Mean GFR in the 10 survivors is 77 ml/min/m2. In 9 of these 10, daily urinary oxalate excretion normalized. Renal function has improved (mean GFR 86 vs. 58 ml/min/m2) but renal oxalate deposits remain in the three recipients of isolated liver grafts. CONCLUSIONS: Our decade-long experience with children with PH-1 supports strategies for early diagnosis and timely liver transplantation. Preemptive isolated liver transplantation should be considered in children who develop the disease during infancy or in those with slowly progressive disease when significant symptoms develop. Combined liver-kidney transplantation is suggested for children with end-stage renal disease.

Efficacy of lamivudine for the treatment of hepatitis B virus infection after liver transplantation in children.

BACKGROUND: There is at present very little information about hepatitis B virus (HBV) infection in children after liver transplantation. This is the first study to assess the safety and efficacy of lamivudine in this patient population. METHODS: We describe three children aged 5-14 years who underwent liver transplantation for fulminant hepatitis A, hyperoxaluria, and cystic fibrosis. Despite adequate immunoprophylaxis, two of the children who were serum hepatitis B surface antigen-positive before transplantation (HBV DNA-negative by hybridization) had a reactivation of the disease, and one had a de novo HBV infection, at 12-18 months after transplantation. Lamivudine 3 mg/kg was administered on a compassionate-use basis for 14-36 months. RESULTS: After 1 month of therapy, HBV DNA disappeared from the serum in all patients by hybridization and in two patients by polymerase chain reaction. In all three children, alanine transaminase levels normalized. One child developed lamivudine resistance after 22 months with no evidence of hepatic decompensation. Repeated liver histological studies revealed progression of hepatic fibrosis in one child. All children remained serum hepatitis B surface antigen- and hepatitis B e antigen-positive. No adverse effects of the drug were noted. CONCLUSION: Lamivudine is beneficial and well tolerated in children with HBV infection after liver transplantation.

Faecal occult blood in children with coeliac disease.

UNLABELLED: It has recently been suggested that in adults with coeliac disease, faecal blood loss may play a role in the development of iron deficiency. A group of 45 children diagnosed with coeliac disease during 1996 and 1997 were therefore prospectively evaluated for the presence of gluten in their diet, iron deficiency anaemia, and faecal occult blood. Sixty children admitted for elective surgery or asthma served as controls. Faecal occult blood was found in four iron deficient children on normal diet, of whom three were newly diagnosed. Occult blood loss disappeared in three of the four children when gluten was removed from their diet. Faecal occult blood was found in 26.7% of children on gluten-containing diet, but not in children on gluten-free diet (P = 0.01), or in control children (P = 0.001). CONCLUSION: Our data suggest that the incidence of occult blood loss in coeliac disease occurs mainly in newly diagnosed cases and responds to a gluten-free diet. Occult blood testing may not be warranted in the absence of iron deficiency anaemia nor in children with iron deficiency anaemia who are on a gluten-free diet.

Serum transferrin receptor in children and adolescents with inflammatory bowel disease.

UNLABELLED: Iron studies are difficult to interpret in patients with chronic inflammatory states such as inflammatory bowel disease (IBD). Serum transferrin receptor (TfR) has been reported to be a reliable tool for the diagnosis of iron deficiency in adults. Our aim was to evaluate the role of serum TfR in diagnosing iron deficiency in children and adolescents with IBD. A total of 63 consecutive patients with IBD, aged 9 to 22 years (median 15 years), were tested for serum haemoglobin level, mean corpuscular volume (MCV), and serum iron, transferrin, ferritin and serum TfR levels. Those found to be anaemic were compared with seven age-matched subjects with iron deficiency anaemia (IDA) and 24 age-matched children without signs of anaemia or inflammation. Of the 63 patients with IBD, 26 had anaemia. Based on ferritin levels and MCV indices, anaemia was classified as IDA in 11 patients and as anaemia of chronic disease (ACD) in 15 patients. Mean serum TfR level in normal controls was 3.5 mg/l (range 1.2-8.2 mg/l). Mean (+/-SD) serum TfR levels were significantly lower in the IBD patients with ACD (5.3 +/- 2.3 mg/l) than in the IBD patients with IDA (8.2 +/- 3.1 mg/l) (P < 0.05). Serum TfR levels above 5 mg/l identified 10/11 IBD patients with IDA. The calculated TfR/ferritin ratio was 84 (range 17-367) for controls and 133 (range 6.4-1840) for IBD patients. A cut-off level of 350 (91% sensitivity, 100% specificity, 100% positive predictive value, 98% negative predictive value) was established for the diagnosis of IDA in IBD. CONCLUSION: The results suggest that serum transferrin receptor is a useful parameter for the diagnosis of iron deficiency in inflammatory bowel disease, in particular, the transferrin receptor/ferritin ratio with a cut-off level > or = 350.

Liver enzyme abnormalities in gram-negative bacteremia of premature infants.

BACKGROUND: Hyperbilirubinemia and liver enzyme abnormalities are commonly observed in sepsis. However, the frequency in premature neonates and the specific relation to gram-negative bacteria are not known. PATIENTS AND METHODS: Charts of all preterm infants who had positive blood cultures for either gram-negative bacteria or coagulase-negative staphylococci were reviewed. Neonates with gram-negative bacteremia (n = 54) were compared with neonates with coagulase-negative staphylococcal bacteremia (n = 31). In addition infants with gram-negative bacteremia and elevated liver enzymes (n = 25) were compared with infants with gram-negative bacteremia and normal liver enzymes (n = 29). RESULTS: Liver enzyme abnormalities accompanied 46.3% (25 of 54) of gram-negative bacteremia and 12.9% (4 of 31) of episodes of coagulase-negative staphylococcal bacteremia (P = 0.002). Serum concentrations of liver enzymes were significantly higher in infants with gram-negative bacteremia than in those with coagulase-negative staphylococcal bacteremia (P < 0.0001), but no difference in alkaline phosphatase serum values was observed. Infants with gram-negative bacteremia and elevated liver enzymes were not fed for a longer period than infants with gram-negative bacteremia and normal liver enzymes (7.3 +/- 6.3 days vs. 4.0 +/- 4.3 days, P = 0.03), and this was accompanied by significant conjugated hyperbilirubinemia (P < 0.0001). Ventilation, total parenteral nutrition and medications were not responsible for the observed differences. Klebsiella pneumoniae bacteremia was commonly associated with elevated liver enzymes (12 of 18), whereas none of the infants with Pseudomonas aeruginosa bacteremia had elevated liver enzymes. CONCLUSIONS: Gram-negative bacteremia is commonly associated with cholestasis in premature neonates. Liver enzyme abnormalities are more common than elevated conjugated bilirubin, not all gram-negative bacteria have the same effect and the lack of enteral feeding seems to play a more significant role than the administration of parenteral nutrition.

Thiamine deficiency in children with congenital heart disease before and after corrective surgery.

BACKGROUND: Malnutrition is common in children with congenital heart disease, while thiamine deficiency (TD) is common in malnutrition, in critically ill children, and in adults with congestive heart failure treated with loop diuretics. Our goal was to determine whether children with congenital heart disease had TD and whether treatment with loop diuretics is related to TD in these patients. METHODS: Twelve children with ventricular septal defect (VSD) treated with furosemide, and 10 children with tetralogy of Fallot (TOF) referred for corrective surgery were consecutively enrolled into a prospective study. Data were collected 24 hours before surgery and 5 days after surgery for nutrition evaluation, medications used, anthropometric measurements, and laboratory markers of malnutrition. Thiamine and pyridoxine deficiencies were evaluated using activated enzyme assays. RESULTS: Seven children (32% of patients) did not meet the recommended daily allowance (RDA) for calories and 18% of patients did not meet the RDA for thiamine intake. Anthropometric measurements were low in both groups, more so in those with VSD, although the difference did not reach statistical significance. Overall, 18% (1/12 with VSD and 3/10 with TOF) of children with congenital heart disease had thiamine deficiency before surgery. Three of the four children with TD had adequate intake of thiamine. Six children (27%) had TD 5 days postsurgery (3 children with VSD and 3 children with TOF). CONCLUSIONS: TD is common in children with congenital heart disease (CHD) referred for corrective surgery both before and after surgery. Our results suggest that neither diuretic treatment nor malnutrition can fully explain the development of TD in these children.

The effect of cisapride on total parenteral nutrition-associated cholestasis in rats.

BACKGROUND: Cholestasis is a frequent problem in patients on total parenteral nutrition. Cisapride has a prokinetic effect on the biliary system, but its effect on hepatic excretory function is unknown. OBJECTIVES: To study the effect of cisapride on TPN-induced cholestasis in a rat model. METHODS: Bile flow and bile salt secretion rate were measured in rats given TPN. There were four groups of 8 to 13 animals each. After a one hour baseline period during which all four groups received i.v. saline infusion, two groups received a TPN solution for another 2 hours, while saline was infused in the two control groups. At the beginning of the second hour, 2 mg/kg cisapride was injected i.v. as a bolus into one experimental and one control group. Bile was collected from the common bile duct. RESULTS: At the end of the third hour, TPN caused a significant reduction in bile flow (P < 0.02) and bile salt secretion rate (P < 0.001) (61.24 vs. 50.74 microliters/min/kg, and 1.173 vs. 0.799 mumol/min/kg, respectively). Addition of cisapride abolished the cholestatic effect of TPN. CONCLUSIONS: Cisapride has a protective effect against TPN-associated cholestasis. This may have clinical significance, and further studies are warranted.

The role of Helicobacter pylori and gastritis in children with recurrent abdominal pain.

BACKGROUND: Recurrent abdominal pain is a common pediatric diagnostic problem. Endoscopy is sometimes performed as part of the evaluation. Although gastritis and/or Helicobacter pylori infection is often present, it is not known if they contribute to the symptomatology. OBJECTIVES: To evaluate the role of either gastritis or H. pylori infection in the symptomatology of children with RAP. PATIENTS AND METHODS: We retrospectively studied two groups of patients, 70 children in each, who had undergone endoscopy. One group was evaluated endoscopically for RAP and the other was a heterogeneous group that underwent endoscopy for indications other than RAP. Biopsies were taken during endoscopy and Giemsa staining was performed for the presence of H. pylori. Triple therapy was given as indicated, and the children were followed for an average of 6 months. RESULTS: Microscopic gastritis was diagnosed in 39 patients (55.7%) of the RAP group and in 31 of the heterogeneous group (44.2%) (NS), and H. pylori was found in 32 patients of the RAP group and in 16 of the heterogeneous group (45.7% vs. 22.8%, P < 0.01). All children with H. pylori, except one in the heterogeneous group, had accompanying gastritis. On the other hand, gastritis without H. pylori infection was seen in 7 children in the RAP group and in 15 of the other. Endoscopy revealed macroscopic abnormalities in 52 of the 70 children with microscopic gastritis. There was a clinical improvement after triple therapy in 28 of 33 children with H. pylori-associated gastritis (84.85%), in 4 of 8 children with gastritis unassociated with H. pylori (50%), and in 8 of 15 without gastritis or H. pylori (53.3%) (P < 0.01 between the H. pylori-associated gastritis and each of the other groups). CONCLUSIONS: H. pylori infection and gastritis may be associated with RAP in a selected subgroup of children. We recommend a complete work-up, including endoscopy and invasive or non-invasive diagnostic modalities for H. pylori, and treatment of the infection.

Chronic hepatitis B virus in children in Israel: clinical and epidemiological characteristics and response to interferon therapy.

OBJECTIVE: To describe the clinical and epidemiological features of hepatitis B virus infection in Israeli children, and to evaluate their response and compliance to therapy. METHODS: We retrospectively studied 51 patients (34 males, 17 females), aged 2-18 years, from several medical centers in Israel. RESULTS: Of the 51 patients, 38 with elevated transaminase, positive hepatitis B e antigen and/or HBV DNA, and histologic evidence of liver inflammation were treated. Interferon was administered by subcutaneous injections three times a week for 3-12 months (dosage range 3-6 MU/m2). Only 16% were native Israelis, while 78% of the children were of USSR origin. A family history of HBV infection was recorded in 25 of the 51 patients (9 mothers, 16 fathers or siblings). Five children had a history of blood transfusion. The histological findings were normal in 3 patients, 24 had chronic persistent hepatitis, 14 had chronic active hepatitis and 2 had chronic lobular hepatitis. Five children also had anti-hepatitis D virus antibodies. Twelve of the 38 treated patients (31.5%) responded to IFN completely, with normalization of the transaminase levels and disappearance of HBeAg and HBV DNA. In no patient was there a loss of hepatitis B surface antigen. The main side effects of IFN were fever in 20 children, weakness in 10, headaches in 9, and anorexia in 6; nausea, abdominal pain, and leukopenia were present in 3 cases each. The response rate was not affected by age, country of origin, alanine/aspartate aminotransferase levels, or histological findings. However, a history of blood transfusion was a predictor of good response, 60% vs 27% (P < 0.05). CONCLUSIONS: We found IFN to be a safe and adequate mode of treatment in children with chronic HBV infection, regardless of their liver histology and transaminase levels. Therefore, in view of the transient side effects associated with this drug, we recommend considering its use in all children with chronic hepatitis B.

Parenteral nutrition-associated cholestasis in preterm neonates: evaluation of ursodeoxycholic acid treatment.

BACKGROUND/OBJECTIVE: Parenteral nutrition is an integral part of the care of premature infants. Cholestatic liver disease is a frequent complication of prolonged parenteral nutrition, especially in premature infants. It has been suggested that ursodeoxycholic acid may alter the course of parenteral nutrition-associated cholestasis in children and adults. We attempted to determine the efficacy of ursodeoxycholic acid in premature infants with parenteral nutrition-associated cholestasis. METHODS: Retrospective chart review of all infants receiving ursodeoxycholic acid for parenteral nutrition-associated cholestasis in a 40 bed neonatal intensive care unit. Efficacy of ursodeoxycholic acid was evaluated by response of bilirubin, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase over a treatment period of at least 1 month. RESULTS: Six infants with parenteral nutrition-associated cholestasis who had received ursodeoxycholic acid for one month were identified. Doses of ursodeoxycholic acid ranged from 15-30 mg/kg/day. Cholestasis appeared at a mean age of 47 +/- 17 (mean +/- SD) days after a mean of 42 +/- 15 days of parenteral nutrition. Transaminase levels decreased in three, and either increased or did not change in the other three infants. Bilirubin levels decreased in all infants. Alkaline phosphatase showed a non significant trend to decreased levels. Consistent improvement in all infants was noted only after 10 days of full enteral nutrition. No toxicity was found during ursodeoxycholic acid treatment. CONCLUSIONS: Ursodeoxycholic acid treatment in premature infants appears to be safe, and leads to an early sustained decrease in bilirubin levels by two weeks of therapy. The response of transaminase levels was not sustained in our small cohort.

Effect of parenteral nutrition on oral intake.

Oral intake following a high density oral supplement (preload) is lower than that after a low density preload. We studied a similar effect of parenteral nutrition on oral intake. Twelve neurologically intact children (8-16 yr) with orthopedic problems and no concurrent illness were included in the study. As part of the inclusion criteria, all patients had documented energy intake for breakfast of +/- 10% on 3 consecutive days. On the fourth day parenteral nutrition equal to 50% of the mean energy intake for breakfast was provided for 4 hours before breakfast and energy intake measured. The composition of the parenteral energy was matched with that of the oral intake. The mean oral energy intake without (470 +/- 90 kcal) and with (458 +/- 64 kcal) parenteral nutrition preload was comparable (p > 0.05). Our conclusion is that parenteral nutrition does not affect oral intake in patients without underlying gastrointestinal disease.

Hepatic artery thrombosis in pediatric liver transplantation: graft salvage after thrombectomy.

Hepatic artery thrombosis (HAT) is a devastating complication that may occur after orthotopic liver transplantation (OLT). A higher incidence has been reported in children. Salvage of the graft by thrombectomy has been suggested as an alternative to re-transplantation. In this study we report the outcome of three children who underwent thrombectomy for HAT. Between January 1992 and June 1998, 14 children (< 17 yrs of age) underwent liver transplantation. Three developed HAT (one a whole-liver graft recipient, age 17; two living-related graft recipients, ages 4 and 4.5 yr). In the first patient, thrombosis of the hepatic artery was associated with scattered areas of parenchymal necrosis on computed tomography. In the two living-related patients, HAT was found incidentally during re-exploration for bleeding (day 2 and day 10). Thrombectomy was performed in all three patients. At 18-24 months after thrombectomy, all three children had normal graft function. In the first patient, complete regeneration of the liver has been documented by computed tomography and a late asymptomatic recurrent thrombosis is suggested by absence of arterial flow on Doppler examination. The hepatic artery is patent in the two living-related recipients. One of these living-related recipients developed ischemic bile duct stricture and underwent successful percutaneous balloon dilatation. We conclude that long-term normal graft function can be achieved by thrombectomy in pediatric liver recipients with HAT, even in the presence of limited parenchymal damage.

Cirrhosis in a child with hypothalamic syndrome and central precocious puberty treated with cyproterone acetate.

UNLABELLED: Before the advent of gonadotropin-releasing-hormone analogues, cyproterone acetate (CPA) had been widely prescribed for the treatment of precocious puberty. Although it is usually well tolerated, liver toxicity has been recognized as a complication of its long-term use. We report the occurrence of cirrhosis in a 10-year-old boy with hypothalamic syndrome and precocious puberty who was treated with CPA for over 50 months. Despite discontinuation of the medication, the liver disease progressed. The patient died of sepsis and multiorgan failure at the age of 14 years. This is the first paediatric report of substantial liver damage and liver toxicity progressing to cirrhosis associated with CPA treatment. CONCLUSION: Prolonged cyproterone acetate treatment may induce cirrhosis. Monitoring of liver function both during treatment and for several months after discontinuation of therapy is recommended.