Persistent abnormal liver fibrosis after weaning off parenteral nutrition in pediatric intestinal failure

Abstract

The aim of this study was to evaluate the long-term effects of pediatric intestinal failure (IF) on liver histology. Altogether, 38 IF patients (median age: 7.2 years; range, 0.2-27) underwent liver biopsy, gastroscopy, abdominal ultrasound, and laboratory tests. Sixteen patients were on parenteral nutrition (PN) after 74 PN months (range, 2.5-204). Twentytwo had weaned off PN 8.8 years (range, 0.3-27) earlier, after 35 PN months (range,. Fifteen transplant donor livers served as controls. Abnormal liver histology was found in 94% of patients on PN and 77% of patients weaned off PN (P 5 0.370). During PN, liver histology weighted with cholestasis (38% of patients on PN versus 0% of patients weaned off PN; P 5 0.003) and portal inflammation (38% versus 9%; P 5 0.050) were found. Fibrosis (88% versus 64%; P 5 0. ; P 5 0.037) were significantly higher during than after weaning off PN. Esophageal varices were encountered in 1 patient after weaning off PN. Metavir stage was associated with small bowel length (r 5 20.486; P 5 0.002) and number of septic episodes (r 5 0.480; P 5 0.002). In a multivariate analysis, age-adjusted small bowel length (ß 5 20.533; P 5 0.001), portal inflammation (ß 5 0.291; P 5 0.030), and absence of an ileocecal valve (ß 5 0.267; P 5 0.048) were predictive for fibrosis stage. Conclusion: Despite resolution of cholestasis and portal inflammation, significant liver fibrosis and steatosis persist after weaning off PN. Extensive small intestinal resection was the major predictor for liver fibrosis stage. (HEPATOLOGY 2013;58:729-738)

Features of liver tissue remodeling in intestinal failure during and after weaning off parenteral nutrition

“…27,28 In pediatric-onset IF, histologic liver fibrosis and steatosis are interrelated and persist for more than a decade after cessation of PN, possibly representing a permanent change. 8,29 Whether the persistent histologic injury represents a progressive disease process has become relevant, because an increasing number of children with neonatal IF Relative liver gene expression, immunohistochemistry, and serum levels of TIMP1 (A, C, E) and MMP7 (B, D, F) in patients currently receiving PN, patients weaned off PN, and controls. Immunostaining of TIMP1 in perisinusoidal hepatocytes and MMP7 in bile ducts were graded visually from 0-3.…”

“…In addition to lobular (0 = absent, 1 = present, and 2 = prominent) and overall fibrosis (Metavir fibrosis stage), cholestasis, portal inflammation, and steatosis were graded as described previously. 8 Immunohistochemistry. Immunostainings were performed using freshly cut, 4-mm sections of formalin-fixed and paraffin-embedded liver samples.…”

“…All patients with pediatric-onset IF treated and followed up with our intestinal rehabilitation program after massive small intestinal resection or prolonged PN at Children's Hospital, Helsinki University Central Hospital, from 1984 to 2010 were reviewed. Of the 52 survivors (93%), 38 underwent ultrasoundguided liver biopsy and serum sampling during general anesthesia for gastroscopy as described previously 8 ; 25 with sufficient liver biopsy material were included in this study.…”

“…4,5 In accordance with experimental studies, PN-dependent children with IF display an overabundance of lipopolysaccharideproducing Proteobacteria in their intestinal microbiota in association with histologic liver injury, intestinal inflammation, and increased levels of serum proinflammatory cytokines. 11 Liver fibrosis is observed with increasing frequency after extensive distal small intestinal resection in children 6,8 and even without a history of PN administration in pigs, 12 supporting an essential role of disturbed intestinal homeostasis in the pathogenesis of IFALD.…”

Neonatal surgery: Towards evidence-based practice and management

“…6,[28][29][30] Crosssectional studies are relatively easy and rapid to perform, while prospective follow-up studies are more time consuming. An inherent limitation in pediatric surgical cross-sectional studies includes a wide age range of patients, which is taken into account when evaluating the results.…”