The outcome of primary liver transplantation from deceased donors in children with body weight < or =10 kg.

Between November 1982 and March 2006, 67 children with body weight < or =10 kg had a primary liver transplantation from deceased donors in our unit. The aim of this study was to analyze the outcome in terms of patient and graft survival and to search for factors affecting this outcome. Overall, one-, three-, five-, and 10-yr primary patient and graft survival rates were 73%, 71%, 66%, 63% and 59%, 56%, 53%, 48%, respectively. Twenty-four of 67 (36%) children died and in the remaining 22 (33%), the first grafts failed and they were retransplanted. Cox regression analysis revealed that a need for retransplantation and urgent transplantation were important predictors for patient survival (p = 0.04 and p = 0.001, respectively). To assess whether the need for retransplantation can be influenced, all study variables were compared between surviving grafts and failed grafts. Cox regression analysis showed that only donor/recipient (D/R) weight ratio proved to be independent predictor for graft survival (p = 0.004). After comparison of graft survival with the long rank test according to different D/R weight ratios (3.0-7.0), the cut-off point for significantly different graft survival approached 4.0. The one-, three-, five-, and 10-yr graft survival for technical variant grafts with a D/R weight ratio <4.0 was 85%, 68%, 68%, and 68% compared with a D/R weight ratio >4.0 was 44%, 38%, 38%, and 30%, respectively (p = 0.02). In summary, patient survival in children with body weight < or =10 kg is determined by urgent transplantation and the need for retransplantation. Graft loss and retransplantation in small children can be prevented by adequate size matching of donor and recipient whereby a D/R weight ratio <4.0 seems to offer the favorable outcome.

Obesity in asylum seekers' children in The Netherlands--the use of national reference charts.

BACKGROUND: Growth assessment can be used to monitor health at individual and population level. For asylum seekers' children with different geographic backgrounds, growth reference values are frequently not available. We assessed nutritional condition and growth of asylum seekers' children upon arrival and follow-up in The Netherlands, using national growth charts, and related these parameters to geographic origin. METHODS: Height and weight of 135 children originating from Africa (n=47), Central Asia (n=41), and Eastern Europe (n=47), were assessed longitudinally (median follow-up 3 years, range 1-8 years). Body-mass-index (BMI) was calculated, and overweight and obesity were defined according the international BMI cut-off values for age and gender. RESULTS: Upon arrival at a median age of 4.5 years (range 0-11.5 years), 13% of the children were small for age (below -2 SD of the Dutch height for age reference), which decreased to 5% during follow-up (P<0.05). During follow-up, 90% of the height measurements in boys and 85% in girls were within the normal range (+/-2 SD) of the Dutch references. The proportion of children with overweight including obesity increased from 15% at arrival to 21% during follow-up (P<0.05). Irrespective of age, children originating from Africa were taller than children from Central Asia or Eastern Europe at follow up (P<0.05). Overweight and obesity was most prominent among children of Eastern Europe. CONCLUSION: Dutch national reference values allow monitoring growth and the development of overweight or obesity in asylum seekers' children in The Netherlands. Prevention strategies to reduce the development of overweight and obesity among these children seem warranted.

Vitamin D levels in children of asylum seekers in The Netherlands in relation to season and dietary intake.

Low dietary intake and limited sun exposure during Dutch winters, in particular when combined with highly pigmented skin, could compromise the vitamin D status of asylum seekers' children in The Netherlands. We determined the vitamin D status of children living in The Netherlands, but originating from Africa, Central Asia, or Eastern Europe. In a subgroup, we reassessed the vitamin D status after the summer, during which the children had been assigned at random to remain unsupplemented or to receive vitamin D supplementation. In total 112 children (median age 7.1 yr, range 2-12 yr) were assessed for serum concentrations of 25-Hydroxyvitamin D [25(OH)D], intact parathyroid hormone (I-PTH) and plasma alkaline phosphatase (ALP). Vitamin D deficiency (VDD) and hypovitaminosis D were defined as 25(OH)D below 30 or 50 nmol/L, respectively. Dietary intake of vitamin D and calcium was estimated using a 24 h recall interview. In mid-spring, 13% of the children had VDD, and 42% had hypovitaminosis D. I-PTH and ALP levels were significantly higher in children with VDD. The dietary intake of vitamin D was below 80% of the recommended daily allowances (RDA) in 94% of the children, but the dietary calcium intake was not significantly related to the s-25(OH)D levels found. After the summer, median s-25(OH)D increased with +35 nmol/L (+85%) and +19 nmol/L (+42%) in children with or without supplementation, respectively. The effect of supplementation was most prominent among African children. VDD and hypovitaminosis D are highly prevalent in mid-spring among asylum seekers' children in The Netherlands. Although 25(OH)D levels increase in African children during Dutch summer months, this does not completely correct the compromised vitamin D status. Our data indicate that children from African origin would benefit from vitamin D supplementation.

Cyclosporine A withdrawal during follow-up after pediatric liver transplantation.

It is unclear whether cyclosporine A (CsA) can be withdrawn safely during follow-up after pediatric liver transplantation. In our transplant program we have been using a strict protocol to withdraw CsA. The aim of this study was to retrospectively assess the effects of CsA withdrawal after pediatric liver transplantation on the incidence of rejection and renal function. Between 1986 and 2001, 91 children received CsA for at least 2 yr after liver transplantation. Specific criteria for eligibility to withdraw CsA were set. In 53 of the 91 children CsA was withdrawn. In 35 patients (66%) withdrawal of CsA did not cause rejection. In these patients the renal function improved compared with baseline values (glomerular filtration rate (GFR) at 1 yr, +16 mL/minute/1.73 m3, P < 0.001; at 2 yr, +10 mL/minute/1.73 m3, P < 0.05). After CsA withdrawal, 18 patients developed rejection (34%), which could be effectively treated by methylprednisolone and restarting CsA. Failure to withdraw CsA was not associated with increased incidence of graft loss. A body weight below 10 kg at the time of transplantation correlated significantly with successful withdrawal of CsA (<10 kg, 85% vs. > 10 kg, 60%; P < 0.05). In conclusion CsA can successfully be withdrawn in a major proportion of selected pediatric liver transplantation patients during follow-up. The success rate is the highest in children with a body weight below 10 kg at the time of transplantation. Successful withdrawal improves renal function, whereas failure to withdraw is not associated with graft loss or persisting morbidity.

The effect of HLA mismatches, shared cross-reactive antigen groups, and shared HLA-DR antigens on the outcome after pediatric liver transplantation.

The aim of this study was to analyze the effect of human leukocyte antigen (HLA) class I and HLA-DR mismatching, sharing cross-reactive antigen groups (CREGs), and sharing HLA-DR antigens on the outcome after pediatric liver transplantation. Outcome parameters were graft survival, acute rejection, and portal fibrosis. A distinction was made between full-size (FSLTx) and technical-variant liver transplantation (TVLTx). A total of 136 primary transplants were analyzed. The effect of HLA on the outcome parameters was analyzed by adjusted multivariate logistic and Cox regression analysis. HLA mismatches, shared CREGs, and shared HLA-DR antigens affected neither overall graft survival nor survival after FSLTx. Survival after TVLTx was superior in case of 2 mismatches at the HLA-DR locus compared to 0 or 1 mismatch (P = 0.01) and in case of no shared HLA-DR antigen compared to 1 shared HLA-DR antigen (P = 0.004). The incidence of acute rejection was not influenced by HLA. The incidence of portal fibrosis could be analyzed in 62 1-yr biopsies and was higher after TVLTx than FSLTx (P = 0.04). The incidence of portal fibrosis after TVLTx with 0 or 1 mismatch at the HLA-DR locus was 100% compared to 43% with 2 mismatches (P = 0.004). After multivariate analysis, matching for HLA-DR and matching for TVLTx were independent risk factors for portal fibrosis. In conclusion, an overall beneficial effect of HLA matching, sharing CREGs, or sharing HLA-DR antigens was not observed. A negative effect was present for HLA-DR matching and sharing HLA-DR antigens on survival after TVLTx. HLA-DR matching might be associated with portal fibrosis in these grafts.

Cyclosporine A-induced reduction of bile salt synthesis associated with increased plasma lipids in children after liver transplantation.

Hyperlipidemia is a common side effect of cyclosporine A (CsA) after solid organ transplantation. CsA also markedly reduces the synthesis rate of bile salts in rats and can inhibit biliary bile salt secretion. It is not known, however, whether CsA inhibits the synthesis of bile salts in humans, and whether the hyperlipidemic effects of CsA are related to bile salt metabolism. Our objective was to assess the effects of CsA on the synthesis rate of bile salts and on plasma triglycerides and cholesterol levels in pediatric liver transplant patients. Before and after discontinuation of CsA treatment after liver transplantation, synthesis rate and pool size of the primary bile salts cholate and chenodeoxycholate were determined using a stable isotope dilution technique and related to plasma lipids. In 6 children (age: 3-16 years) CsA treatment was discontinued at 2 years (median 2.3 years) after liver transplantation. Discontinuation of CsA increased synthesis rate of chenodeoxycholate (+38%, P <.001) and cholate (+21%, P <.05) and the pool size of chenodeoxycholate (+54%, P <.001). Discontinuation of CsA decreased plasma levels of cholesterol (-18%, P <.05) and triglycerides (-23%, P <.05). Bile salt synthesis rate appeared to be inversely correlated with plasma cholesterol (Spearman rank correlation coefficient [r(s)] = -0.82, P <.01) and plasma triglyceride levels (r(s) = -0.62, P <.05). In conclusion, CsA inhibits bile salt synthesis and increases plasma concentration of cholesterol and triglycerides in pediatric liver transplant patients. Suppression of bile salt synthesis by long-term CsA treatment may contribute to hyperlipidemia and thus to increased risk for cardiovascular disease.

In vivo imaging of hepatobiliary transport function mediated by multidrug resistance associated protein and P-glycoprotein.

Multidrug resistance associated proteins (MRPs) and P-glycoprotein (P-gp) are involved in hepatobiliary transport of various compounds. Our aim was (1) to define transporter specificity of the cholescintigraphic agents 99mTc-HIDA and 99mTc-MIBI, which are used clinically for myocardial perfusion measurements; and (2) to deduce MRP and P-gp functions in vivo from hepatic 99mTc kinetics. Accumulation of radioactivity was measured in the human tumor cell lines GLC4, GLC4/ADR150x (MRP1-overexpressing/P-gp-negative) and GLC4/P-gp (P-gp-overexpressing). Bile secretion was quantified in untreated and in glutathione-depleted control and MRP2-deficient (GY/TR-) rats. Hepatobiliary transport was measured using a gamma camera in both types of rats. 99mTc-HIDA accumulated 5.8-fold less in GLC4/ADR150x calls than in GLC4 or GLC4/P-gp cells. In GLC4/ADR150x, the cellular 99mTc-HIDA content was increased 3.4-fold by the MRP1,2 inhibitor MK571 (50 microM), while MK571 had no measurable effect in GLC4 and GLC4/P-gp cells. 99mTc-MIBI accumulated less in GLC4/P-gp and GLC4/ADR150x cells than in GLC4 cells. Bile secretion of 99mTc-HIDA was impaired in GY/TR- compared to control rats and not affected by glutathione depletion in GY/TR- rats. Hepatic secretion of 99mTc-HIDA was slower in GY/TR- (t1/2 40 min) than in control rats (t1/2 7 min). Bile secretion of 99mTc-MIBI was similar in both rat strains and impaired by glutathione depletion in control rats only, indicating compensatory activity of additional transporter(s) in GY/TR- rats. 99mTc-HIDA is transported only by MRP1,2 only, while 99mTc-MIBI is transported by P-gp and MRP1,2. The results indicate that hepatic P-gp and MRP1,2 function can be assessed in vivo by sequential use of both radiopharmaceuticals.

Development and validation of challenge materials for double-blind, placebo-controlled food challenges in children.

BACKGROUND: The use of double-blind, placebo-controlled food challenges (DBPCFCs) is considered the gold standard for the diagnosis of food allergy. Despite this, materials and methods used in DBPCFCs have not been standardized. OBJECTIVE: The purpose of this study was to develop and validate recipes for use in DBPCFCs in children by using allergenic foods, preferably in their usual edible form. METHODS: Recipes containing milk, soy, cooked egg, raw whole egg, peanut, hazelnut, and wheat were developed. For each food, placebo and active test food recipes were developed that met the requirements of acceptable taste, allowance of a challenge dose high enough to elicit reactions in an acceptable volume, optimal matrix ingredients, and good matching of sensory properties of placebo and active test food recipes. Validation was conducted on the basis of sensory tests for difference by using the triangle test and the paired comparison test. Recipes were first tested by volunteers from the hospital staff and subsequently by a professional panel of food tasters in a food laboratory designed for sensory testing. Recipes were considered to be validated if no statistically significant differences were found. RESULTS: Twenty-seven recipes were developed and found to be valid by the volunteer panel. Of these 27 recipes, 17 could be validated by the professional panel. CONCLUSION: Sensory testing with appropriate statistical analysis allows for objective validation of challenge materials. We recommend the use of professional tasters in the setting of a food laboratory for best results.

Comparison of near infrared reflectance analysis of fecal fat, nitrogen and water with conventional methods, and fecal energy content.

OBJECTIVES: To evaluate Near-Infrared Analysis (NIRA) method for determining fecal fat, water and nitrogen. DESIGN AND METHODS: The results of fecal fat, water and nitrogen by NIRA were compared with results of van de Kamer and Acid Steatocrit (AS), Dumas and vacuum drying methods for fat, nitrogen and water respectively. Results of fat determining methods were also compared with total fecal energy as obtained by bomb calorimeter. RESULTS: NIRA results correlated significantly (p < 0.001) with standard methods for nitrogen (r = 0.79), fat (r = 0.84 and r = 0.88 for van de Kamer and AS respectively) and water (r = 0.91). The limits of agreement for nitrogen and fat results were too wide for the methods to be used interchangeably. The fecal fat results correlated significantly (p < 0.001) with fecal energy results. CONCLUSION: NIRA may be valuable for monitoring malabsorption but the diagnostic value remains to be determined.

Graft loss after pediatric liver transplantation.

OBJECTIVE: To describe the epidemiology and causes of graft loss after pediatric liver transplantation and to identify risk factors. SUMMARY BACKGROUND DATA: Graft failure after transplantation remains an important problem. It results in patient death or retransplantation, resulting in lower survival rates. METHODS: A series of 157 transplantations in 120 children was analyzed. Graft loss was categorized as early (within 1 month) and late (after 1 month). Risk factors were identified by analyzing recipient, donor, and transplantation variables. RESULTS: Kaplan-Meier 1-month and 1-, 3-, and 5-year patient survival rates were 85%, 82%, 77%, and 71%, respectively. Graft survival rates were 71%, 64%, 59%, and 53%, respectively. Seventy-one of 157 grafts (45%) were lost: 18 (25%) by death of patients with functioning grafts and 53 (75%) by graft-related complications. Forty-five grafts (63%) were lost early after transplantation. Main causes of early loss were vascular complications, primary nonfunction, and patient death. Main cause of late graft loss was fibrosis/cirrhosis, mainly as a result of biliary complications or unknown causes. Child-Pugh score, anhepatic phase, and urgent transplantation were risk factors for early loss. Donor age, donor/recipient weight ratio, blood loss, and technical-variant liver grafts were risk factors for late loss. CONCLUSIONS: To prevent graft loss after pediatric liver transplantation, potential recipients should be referred early so they can be transplanted in an earlier phase of their disease. Technical-variant liver grafts are risk factors for graft survival. The logistics of the operation need to be optimized to minimize the length of the anhepatic phase.