Features of liver tissue remodeling in intestinal failure during and after weaning off parenteral nutrition.
Intestinal failure is associated frequently with liver injury, which persists after weaning off parenteral nutrition. We compared features of liver remodeling in intestinal failure during and after weaning off parenteral nutrition.



Liver biopsies and serum samples were obtained from 25 intestinal failure patients at a median age of 9.7 years (interquartile range: 4.6-18) and from age-matched control patients. Seven patients had been receiving parenteral nutrition for 53 months (22-160), and 18 patients had been weaned off parenteral nutrition 6.3 years (2.4-17) earlier, after having received parenteral nutrition for 10 months (3.3-34). Expression of alpha-smooth muscle actin, collagen 1, proinflammatory cytokines, growth factors, and matrix metalloproteinases (MMPs) was measured.



Significant increases in immunohistochemical expression of alpha-smooth muscle actin and collagen 1 were observed predominantly in portal areas and were similar to increases seen in patients currently receiving parenteral nutrition and in patients weaned off parenteral nutrition. Gene and protein expressions of alpha-smooth muscle actin and collagen were interrelated. Gene expression of ACTA2, encoding alpha-smooth muscle actin, was increased only in patients who were receiving parenteral nutrition currently. Comparable upregulation of interleukin-1 (α and ß), epidermal growth factor, integrin-ß6, and MMP9 gene expression was observed in both patient groups, irrespective of whether they were receiving parenteral nutrition currently. Liver expression and serum levels of TIMP1 and MMP7 were increased only in the patients on parenteral nutrition currently but were not increased after weaning off parenteral nutrition.



Intestinal failure is characterized by abnormal activation of hepatic myofibroblast and accumulation of collagen both during and after weaning off parenteral nutrition. Persistent transcriptional upregulation of proinflammatory and fibrogenic cytokines after weaning off parenteral nutrition suggests that factors other than parenteral nutrition may contribute to intestinal failure-associated liver disease.
Section of Pediatric Surgery, Pediatric Liver and Gut Research Group, Children's Hospital, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.
Annika
A
Mutanen
Department of Pathology, HUSLAB, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.
Jouko
J
Lohi
Department of Oral and Maxillofacial Diseases, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.
Timo
T
Sorsa
Department of Pediatric Nephrology and Transplantation, Children's Hospital, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.
Hannu
H
Jalanko
Section of Pediatric Surgery, Pediatric Liver and Gut Research Group, Children's Hospital, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland. Electronic address: mikko.pakarinen@hus.fi.
Mikko P
MP
Pakarinen
D000199:Actins / Q000378:metabolism; D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D024042:Collagen Type I / Q000378:metabolism; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D007410:Intestinal Diseases / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D010288:Parenteral Nutrition; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D014886:Weaning
D000199:Actins; D024042:Collagen Type I; D053583:Interleukin-1beta; D019715:Tissue Inhibitor of Metalloproteinase-1; D020782:Matrix Metalloproteinases