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.