title: Incidence, prevention, and treatment of parenteral nutrition-associated cholestasis and intestinal failure-associated liver disease in infants and children: a systematic review.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Surgery, UCL Institute of Child Health, London, UK.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lauriti
authors.forename: Augusto
authors.initials: A
authors.lastname: Zani
authors.forename: Roberto
authors.initials: R
authors.lastname: Aufieri
authors.forename: Mara
authors.initials: M
authors.lastname: Cananzi
authors.forename: Pierluigi Lelli
authors.initials: PL
authors.lastname: Chiesa
authors.forename: Simon
authors.initials: S
authors.lastname: Eaton
authors.forename: Agostino
authors.initials: A
authors.lastname: Pierro
mesh_terms: D001663:Bilirubin / Q000097:blood; D002648:Child; D002779:Cholestasis / Q000150:complications / Q000628:therapy*; D002149:Energy Intake; D006801:Humans; D007223:Infant; D007410:Intestinal Diseases / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control*; D008107:Liver Diseases / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control*; D015201:Meta-Analysis as Topic; D010288:Parenteral Nutrition / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D001663:Bilirubin
keywords: child; cholestasis; intestinal failure; liver disease; parenteral nutrition