SERUM INSULIN-LIKE GROWTH-FACTORS AND THEIR BINDING-PROTEINS IN PATIENTS WITH HEPATIC-FAILURE AND AFTER LIVER-TRANSPLANTATION

The liver is the major source of circulating insulin-like growth facto r-I and -II (IGF-I and IGF-Il) and several of their binding proteins ( BPs). This study examined the effects of end-stage liver disease (ESLD ) and subsequent liver transplantation (LT) an serum levels of these g rowth factors and their BPs in four children and six adults far up to 2 years. Serum IGF-I and IGF-II were quantified by radioimmunoassay (R IA), IGFBP-3 by immunoradiometric assay (IRMA), and changes in IGFBP-1 , -2, -3, and -4 were estimated by Western ligand blotting (WLB). In s evere hepatic disease, serum concentrations of IGF-I (10 +/- 5 ng/mL) and IGF-II (126 +/- 32 ng/mL) were significantly (P < .01) less than i n 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 IG F-II (627 +/- 38 ng/mL) were within normal limits and remained so for the duration of the study. Patients exhibited considerable variation n ot only in the rate of achieving normal IGF-I and IGF-II concentration s, but also in the ultimate height and stability of these peptide leve ls. Serum IGFBP-3 in hepatic failure (580 +/- 140 ng/mL) was significa ntly (P < .05) lower than in controls (2,900 +/- 220 ng/ml) and increa sed to normal levels (3,650 +/- 360 ng/mL) 2 to 14 weeks after LT. Ser um 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 hep atic failure and their subsequent restoration after LT probably result primarily from the reduced number of functional hepatocytes in ESLD a nd their subsequent replacement by healthy hepatic tissue. These chang es may also result from hormonal alterations and nutritional deficienc ies known to exist in patients with severe liver dysfunction, which ar e corrected by LT. We conclude that Lf in patients with severe hepatic insufficiency enhances the potential for normal cell growth and repli cation by restoring serum IGF-I, IGF-II, and IGFBP-3 concentrations to normal concomitantly with the improvement in hormonal and nutritional status. Copyright (C) 1998 by W.B. Saunders Company.