Parenteral plant sterols and intestinal failure-associated liver disease in neonates.

OBJECTIVES: We prospectively evaluated incidence of prolonged (>28 days) parenteral nutrition (PN), associated complications, and significance of parenteral plant sterols (PS) in neonatal intestinal failure-associated liver disease (IFALD) compared with children. METHODS: We recruited 28 neonates (mean age 50 days, range 28-126) and 11 children (6.9 y, 2.1-16.6) in all of Finland. Patients underwent repeated measurements of serum cholesterol, noncholesterol sterols, including PS, cholestanol and cholesterol precursors, and liver biochemistry during and 1 month after discontinuation of PN. Healthy matched neonates (n=10) and children (n=22) served as controls. RESULTS: IFALD occurred more frequently among neonates (63%) than children (27%; P<0.05). Ratios of serum PS, including stigmasterol, sitosterol, avenasterol, and campesterol, and total PS were increased among neonates compared with healthy controls and children on PN by 2- to 22- and 2- to 5-fold (P<0.005), respectively. Neonates with IFALD had significantly higher ratios of serum PS and cholestanol compared with neonates without IFALD (P<0.05). Total duration of PN associated with serum cholestanol, stigmasterol, avenasterol, alanine aminotransferase, and aspartate aminotransferase (r=0.472-0.636, P<0.05). Cholestanol and individual serum PS, excluding campesterol, reflected direct bilirubin (r=0.529-0.688, P<0.05). IFALD persisted after discontinuation of PN in 25% of neonates with 4.2- and 2.2-times higher ratios of serum stigmasterol and cholestanol compared with neonates without IFALD (P<0.05). CONCLUSIONS: Frequent occurrence of IFALD among neonates on PN displays an association to duration of PN and markedly increased serum PS, especially stigmasterol, in comparison to healthy neonates and children on PN. Striking accumulation of parenteral PS may contribute to IFALD among neonates.

Effects of long-term parenteral nutrition on serum lipids, plant sterols, cholesterol metabolism, and liver histology in pediatric intestinal failure.

BACKGROUND AND OBJECTIVE: Plant sterols (PS) in parenteral nutrition (PN) may contribute to intestinal failure-associated liver disease. We investigated interrelations between serum PS, liver function and histology, cholesterol metabolism, and characteristics of PN. PATIENTS AND METHODS: Eleven patients with intestinal failure (mean age 6.3 years) receiving long-term PN were studied prospectively (mean 254 days) and underwent repeated measurements of serum lipids, noncholesterol sterols, including PS, and liver enzymes. PS contents of PN were analyzed. Liver biopsy was obtained in 8 patients. Twenty healthy children (mean age 5.7 years) served as controls. RESULTS: Median percentage of parenteral energy of total daily energy (PN%) was 48%, including 0.9 g · kg(-1) · day(-1) of lipids. Respective amounts of PN sitosterol, campesterol, avenasterol, and stigmasterol were 683, 71, 57, and 45 µg · kg(-1) · day(-1). Median serum concentrations of sitosterol (48 vs 7.5 µmol/L, P < 0.001), avenasterol (2.9 vs 1.9, P < 0.01), stigmasterol (1.9 vs 1.2, P < 0.005), but not that of campesterol (9.8 vs 12, P = 0.22), were increased among patients in relation to controls, and correlated with PN% (r = 0.81-0.88, P < 0.005), but not with PN fat. Serum cholesterol precursors were higher in patients than in controls. Serum liver enzymes remained close to normal range. Glutamyl transferase correlated with serum PS (r = 0.61-0.62, P < 0.05). Liver fibrosis in 5 patients reflected increased serum PS (r = 0.55-0.60, P = 0.16-0.12). CONCLUSIONS: Serum PS moderately increase during olive oil-based PN, and correlate positively with PN% and glutamyl transferase. Despite well-preserved liver function, histology often revealed significant liver damage.

Long-term controlled outcomes after autologous intestinal reconstruction surgery in treatment of severe short bowel syndrome.

AIM: The aim of this study was to analyze outcomes of severe short bowel syndrome (SBS) treated with autologous intestinal reconstruction (AIR) surgery to facilitate independence of parenteral nutrition (PN). METHODS: PN dependence, growth, nutritional status, liver function, and survival were comparatively assessed in SBS children treated with (n=10) or without (n=18) AIR surgery. RESULTS: Median follow-up was 9.2 (4.9-14) years. Residual small intestinal length was 28 cm at birth. A total of 13 AIR procedures were performed at median age of 16 (11-41) months: serial transverse enteroplasty (STEP; n=8), longitudinal lengthening and tailoring (LILT; n=2), and tapering enteroplasty (n=3). Following STEP and LILT, length of the remaining small intestine increased by 19 (15-38) cm or 43% (38%-64%). Two children required repeat STEP due to recurrence of symptoms and bowel re-dilatation. Median duration of PN was 12 (11-17) months before and 14 (0-19) months after AIR. Eight children remain off PN 6.9 (3.6-9.7) years after surgery, and one with ultra short bowel (12 cm) receives 12% of energy as PN - all with reassuring growth and nutritional status and normal liver function. Actuarial PN dependence, including those who died on PN, was similar (P=0.19) with or without AIR surgery being 30% and 20% at four years, respectively. Complications of AIR surgery (lymphocele, bowel obstruction, and staple line bleeding) resolved without operative interventions. Survival was 90% with and 83% without AIR procedures. CONCLUSIONS: AIR surgery can provide long-term survival, independence of PN, and satisfactory general health in selected children with severe SBS.

Surgical treatment and outcomes of severe pediatric intestinal motility disorders requiring parenteral nutrition.

AIM: The aim of this study was to characterize outcomes of children with severe intestinal motility disorders (IMD) requiring parenteral nutrition (PN). METHODS: Twenty consecutive children with primary IMD requiring long-term PN between 1984 and 2010 were included. Median (interquartile range) follow-up was 13.1 (5.2-20.1) years. Treatment, PN dependence, growth, nutritional status, liver function, and survival were assessed. RESULTS: Underlying etiology included chronic intestinal pseudo obstruction (CIPO; n=8) and Hirschsprung disease with extensive aganglionosis (n=12). CIPO and aganglionosis patients had 100 (86-100%) and 29 (19-40%) of age-adjusted small bowel length remaining, respectively. In order to facilitate enteral tolerance and avoid PN-associated liver disease, short aganglionic segment (40 cm) was left in situ in four of five cases, with aganglionosis extending to duodenojejunal flexure combined with Ziegler myectomy-myotomy in two. Six of seven children with aganglionosis extending into mid small intestine underwent staged jejunoanal pull-through. Feeding/venting gastrostomies (n=13) or jejunostomies were commonly employed. Probability of PN dependence owing to IMD was markedly increased in relation to short bowel syndrome (70 versus 19% at 5 years, P<0.0001). Two (10%) patients developed end-stage liver disease. A total of 11 (55%) patients (5 CIPO and 6 aganglionosis) weaned off PN after 8.2 years (1.8-17 years), including two patients after intestinal transplantation (ITx). Two children died before ITx-era giving overall survival of 90%. Survivors had well-preserved liver function, growth, and nutritional status. CONCLUSIONS: Despite high PN dependence, long-term survival is achievable in the majority of children with IMD requiring PN. A wide repertory of surgical options including ITx is required for optimal outcomes.

Cholesterol metabolism in pediatric short bowel syndrome after weaning off parenteral nutrition.

BACKGROUND: Small intestine essentially regulates cholesterol homeostasis. AIMS: To evaluate cholesterol metabolism in short bowel syndrome (SBS). METHODS: Cholesterol precursors (e.g., cholestenol, desmosterol and lathosterol) and plant sterols (campesterol and sitosterol), respective markers of cholesterol synthesis and absorption, were determined in SBS patients (n=12) an average of 31 months after weaning off parenteral nutrition and in age-matched controls (n=80). RESULTS: Among patients, serum cholesterol precursor sterol to cholesterol ratios were 2-10 times higher (P<0.0001 for each). Those without any remaining ileum had 1.2-2.8 times higher precursor sterol to cholesterol ratios than those with an ileal remnant (P<0.05 for each). Serum cholesterol concentration, campesterol/cholesterol and campesterol/sitosterol were 34-39% lower (P<0.05 for each) in relation to controls. Bile acid absorption was markedly impaired (2.4 (0.2-3.2)%). Plant sterol ratios reflected the absolute length of remaining jejunum (r=0.625-0.663), and precursor sterol ratios inversely that of ileum (r=-0.589 to 0.750, P<0.05 for all). CONCLUSION: After weaning off parenteral nutrition, patients with pediatric onset SBS continue to have marked intestinal malabsorption of bile acids and moderate cholesterol malabsorption resulting in decreased serum cholesterol despite a marked compensatory increase in cholesterol synthesis.