Serum insulin-like growth factors and their binding proteins in patients with hepatic failure and after liver transplantation.
Schalch DS. Kalayoglu M. Pirsch JD. Yang H. Raslich M. Rajpal S.
Department of Medicine, University of Wisconsin School of Medicine, Madison, USA.
The liver is the major source of circulating insulin-like growth factor-I and -II (IGF-I and IGF-II) and several of their binding proteins (BPs). This study examined the effects of end-stage liver disease (ESLD) and subsequent liver transplantation (LT) on serum levels of these growth factors and their BPs in four children and six adults for up to 2 years. Serum IGF-I and IGF-II were quantified by radioimmunoassay (RIA), IGFBP-3 by immunoradiometric assay (IRMA), and changes in IGFBP-1, -2, -3, and -4 were estimated by Western ligand blotting (WLB). In severe hepatic disease, serum concentrations of IGF-I (10 +/- 5 ng/mL) and IGF-II (126 +/- 32 ng/mL) were significantly (P < .01) less than in normal controls (170 +/- 37 and 590 +/- 41 ng/mL, respectively). One year following LT, the mean levels of IGF-I (344 +/- 55 ng/mL) and IGF-II (627 +/- 38 ng/mL) were within normal limits and remained so for the duration of the study. Patients exhibited considerable variation not only in the rate of achieving normal IGF-I and IGF-II concentrations, but also in the ultimate height and stability of these peptide levels. Serum IGFBP-3 in hepatic failure (580 +/- 140 ng/mL) was significantly (P < .05) lower than in controls (2,900 +/- 220 ng/mL) and increased to normal levels (3,650 +/- 360 ng/mL) 2 to 14 weeks after LT. Serum levels of IGFBP-1, -2, and -4 before and after LT were variable but usually remained within normal limits compared with control sera. The decreases observed in IGF-I, IGF-II, and IGFBP-3 in patients with hepatic failure and their subsequent restoration after LT probably result primarily from the reduced number of functional hepatocytes in ESLD and their subsequent replacement by healthy hepatic tissue. These changes may also result from hormonal alterations and nutritional deficiencies known to exist in patients with severe liver dysfunction, which are corrected by LT. We conclude that LT in patients with severe hepatic insufficiency enhances the potential for normal cell growth and replication by restoring serum IGF-I, IGF-II, and IGFBP-3 concentrations to normal concomitantly with the improvement in hormonal and nutritional status.