Incidence, Prevention, and Treatment of Parenteral Nutrition-Associated Cholestasis and Intestinal Failure-Associated Liver Disease in Infants and Children: A Systematic Review

Department of Surgery, UCL Institute of Child Health, London, UK.
Journal of Parenteral and Enteral Nutrition (Impact Factor: 3.14). 07/2013; 38(1). DOI: 10.1177/0148607113496280
Source: PubMed

ABSTRACT Cholestasis is a significant life-threatening complication in children on parenteral nutrition (PN). Strategies to prevent/treat PN-associated cholestasis (PNAC) and intestinal failure-associated liver disease (IFALD) have reached moderate success with little supporting evidence. Aims of this systematic review were (1) to determine the incidence of PNAC/IFALD in children receiving PN for ≥14 days and (2) to review the efficacy of measures to prevent/treat PNAC/IFALD. Methods: Of 4696 abstracts screened, 406 relevant articles were reviewed, and studies on children with PN ≥14 days and cholestasis (conjugated bilirubin ≥ 2 mg/dL) were included. Analyzed parameters were (1) PNAC/IFALD incidence by decade and by PN length and (2) PNAC/IFALD prevention and treatment (prospective studies). Results: Twenty-three articles (3280 patients) showed an incidence of 28.2% and 49.8% of PNAC and IFALD, respectively, with no evident alteration over the last decades. The incidence of PNAC was directly proportional to the length of PN (from 15.7% for PN ≤1 month up to 60.9% for PN ≥2 months; P < .0001). Ten studies on PNAC met inclusion criteria. High or intermediate-dose of oral erythromycin and aminoacid-free PN with enteral whey protein gained significant benefits in preterm neonates (P < .05, P = .003, and P < .001, respectively). None of the studies reviewed met inclusion criteria for treatment. Conclusions: The incidence of PNAC/IFALD in children has no obvious decrease over time. PNAC is directly correlated to the length of PN. Erythromycin and aminoacid-free PN with enteral whey protein have shown to prevent PNAC in preterm neonates. There is a lack of high-quality prospective studies, especially on IFALD.

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    ABSTRACT: Introduction Parenteral nutrition-associated cholestasis (PNAC) is a complication of long-term parenteral nutrition (PN). Removal of lipids may reverse PNAC but compromises the energy to ensure infant growth. The purpose of this study was to test whether a low-fat, high-carbohydrate PN regimen, which prevents and reverses PNAC in adults, could do the same in infants. This regimen could potentially avoid the problem of diminished energy input after removing nutritional lipids. Methods Infants developing PNAC over a 2-year period were started on a low-fat PN regimen with calories primarily from carbohydrates. The fat-free PN, containing 314 kJ/ml, was provided 5-6 times a week and fat, including essential fatty acids and fat-soluble vitamins, 1-2 times a week. Enteral feeding was continued according to individual tolerance. Results The study included 10 infants with short bowel syndrome (six with intestinal failure due to necrotizing enterocolitis, one with gastroschisis, one with complications due to unrecognized anal atresia and two with midgut volvulus). Median duration of PN with fat before initiating the low-fat regime was 69 days (25-75 % percentile: 41-75 days), and mean s-bilirubin was 139 mu mol/l (range 87-323 mu mol/l). Median duration with low-fat regimen was 69 days (25-75 % percentile: 18-123 days). Bilirubin reversed to normal (<50 lmol/l) in all infants. Seven children showed catch-up growth. No essential fatty acid deficiency, steatosis or deaths were observed. Conclusions A low-fat, high-carbohydrate PN regimen together with enteral feeding is well tolerated and may be used in reversing liver disease in PN-dependent infants without compromising growth.
    Digestive Diseases and Sciences 08/2014; 60(1). DOI:10.1007/s10620-014-3317-x · 2.55 Impact Factor
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    ABSTRACT: Background/Aim: Development of hepatic dysfunction is a well-recognized complication of total parenteral nutrition in preterm infants. Previous studies reported the incidence of total parenteral nutrition–associated cholestasis and described possible contributing factors to its pathogenesis, but little is done trying to determine its possible predictive risk factors. The aims of this study was to determine the incidence of total parenteral nutrition–associated cholestasis and to develop a possible predictive model for its occurrence. Patients and Methods: A review of medical records of all very low birth weight infants admitted to neonatal intensive care unit at King Khalid University Hospital, Riyadh, Saudi Arabia, between January 2001 and December 2003 was carried out. The infants were divided into two groups: Cholestasis and noncholestasis, based on direct serum bilirubin level >34 μmol/L. A multivariate logistic regression analysis was performed to calculate the statistical significance of risk factors. Receiver–operating characteristic curve was used to determine the optimal cutoff points for the significant risk factors and to calculate their sensitivity and specificity. The level of significance was set at P ≤ 0.05. Results: A total of 307 patients were included in the analysis. The incidence of cholestasis in the whole population was 24.1% (74 patients). Infants with cholestasis had a lower birth weight, 735.4 ± 166.4 g vs. 1185.0 ± 205.6 g for noncholestasis group (P < 0.001), whereas the mean gestational age for the two groups was 25.4 ± 2.1 week and 28.9 ± 2.1 week, respectively (P < 0.001). The significant risk factors for the development of cholestasis were birth weight (P = 0.006) with an odds ratio of 0.99 [95% confidence interval (CI), 0.98, 0.99]; sensitivity of 92%, specificity of 87%; and total parenteral nutrition duration (P < 0.001) with an odds ratio of 1.18 (95% CI, 1.10, 1.27); sensitivity of 96%, specificity of 89%. Conclusions: A lower birth weight and longer duration of total parenteral nutrition were strong predictive risk factors for the development of cholestasis in preterm infants.
    Saudi Journal of Gastroenterology 09/2014; 20(5):293-296. DOI:10.4103/1319-3767.141688 · 1.22 Impact Factor


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Feb 14, 2015