Transforming growth factor-β1 in plasma and liver of children with liver disease

Jeffrey N. Rosensweig, Masako Omori, Kathleen Page, Carol J. Potter, Elizabeth J. Perlman, Snorri S. Thorgeirsson, Kathleen B. Schwarz

Research output: Contribution to journalArticlepeer-review

Abstract

Although several liver diseases of childhood, particularly biliary atresia (BA) and cystic fibrosis (CF) liver disease (CFLD) are characterized by hepatic fibrosis, the pathogenesis of this process is incompletely understood. The cytokine transforming growth factor-β1 (TGF-β1) has been implicated in hepatic fibrosis in experimental animals, in which both the hepatic expression and plasma concentration of this cytokine are increased. The objective of our study was to determine whether there are similar alterations of TGF-β1 in patients with hepatic fibrosis secondary to either BA and/or CFLD. The study design was as follows. In study 1, plasma TGF-β1 was assessed by ELISA in 9 children with BA undergoing liver transplantation, 11 patients with CFLD, and appropriate control subjects. In study 2, hepatic expression of TGF-β1 protein (assessed immunohistochemically) and hepatic fibrosis were scored semiquantitatively, on a 1-3 scale, by blinded investigators, in archival liver biopsy specimens from 10 children with BA, 10 with CFLD, and from 10 older children with normal hepatic histology, as well as in 4 patients with liver diseases of various etiologies. Simultaneous plasma and liver TGF-β1 studies were performed in 8 patients with liver disease. Results were as follows. Plasma TGF-β1 values were inversely correlated with age in healthy subjects (r = -0.54, p < 0.0001). The plasma TGF-β1 protein of children with BA was decreased (13 ± 2 ng/mL) compared with values for healthy children (42 ± 6 ng/mL, n - 10, p < 0.005). Similarly, the plasma TGF-β1 concentration in patients with CFLD was also decreased compared with values for children with CF and normal serum liver profiles (n = 14) (2 ± 1 ng/mL versus 12 ± 1, p < 0.05). However, the plasma TGF-β1 concentration was increased in two patients with other types of liver disease. The hepatic expression of TGF-β1 was increased in the presence of hepatic fibrosis in all types of liver diseases studied. Forty- six percent of patients had both marked hepatic fibrosis and marked TGF-β1 labeling; 86% of samples without fibrosis showed no TGF-β1 labeling, p = 0.007. In conclusion, these studies have established the association of hepatic TGF-β1 protein and hepatic fibrosis in several common liver diseases of childhood. Our data also suggest that, in children, plasma TGF-β1 does not appear to be a useful marker of hepatic expression of this cytokine.

Original languageEnglish (US)
Pages (from-to)402-409
Number of pages8
JournalPediatric research
Volume44
Issue number3
DOIs
StatePublished - Sep 1998

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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