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      Insulin-Like Growth Factors and Insulin-Like Growth Factor Binding Proteins in Adult Patients with Severe Liver Disease before and after Orthotopic Liver Transplantation

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          Abstract

          Introduction: The liver is the main source of serum insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) and the concentration of these proteins might reflect liver function. Methods: In a retrospective longitudinal study we examined serum levels of total and free IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3 and IGFBP-6 in 21 adult patients with end-stage liver disease before and after orthotopic liver transplantation (LTX) by sensitive and specific RIAs. In each patient, the mean value of at least three measurements before and after LTX was calculated. Results: Before LTX, serum levels of total and free IGF-I, IGF-II, IGFBP-3 were low and showed a rapid and significant increase in almost all patients after successful LTX (total IGF-I: 30 ± 7 vs. 256 ± 30 ng/ml, p < 0.001; free IGF-I: 1.3 ± 0.3 vs. 3.5 ± 0.6 ng/ml, p < 0.01; IGF-II: 177 ± 28 vs. 618 ± 30 ng/ml, p < 0.001; IGFBP-3: 1,230 ± 136 vs. 3,665 ± 264 ng/ml, p < 0.001). In contrast, IGFBP-1 was found to be high immediately before LTX, and declined to normal levels after LTX (210 ± 40 vs. 90 ± 15 ng/ml, p < 0.01), while IGFBP-2 did not show any significant changes (1,154 ± 296 vs. 1,303 ± 192 ng/ ml). Positive correlations were found between IGF-I, IGF-II or IGFBP-3, and serum pseudocholinesterase (R = 0.50, 0.72 and 0.61 respectively, p < 0.001). Negative correlations were found between IGF-I, IGF-II or IGFBP-3, and prothrombin time (R = 0.50, 0.59 and 0.51 respectively, p < 0.001). Conclusion: Patients with severe liver disease show decreased levels of total and free IGF-I, IGF-II and IGFBP-3, and increased levels of IGFBP-1. These abnormalities are promptly normalized after successful LTX. Thus, serum levels of IGF-I, IGF-II and IGFBP-3 might be useful parameters for the assessment of liver function.

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          Insulin-like growth factor-I serum concentrations and patterns of insulin-like growth factor binding proteins in patients with chronic liver disease.

          Serum concentrations of insulin-like growth factor-I are decreased in liver cirrhosis. However, this growth factor is bound for the most part to specific binding proteins that are known to modulate biological actions. Plasma insulin-like growth factor binding proteins are predominantly synthesized in the liver. The effect of liver disease on basal and on growth hormone-stimulated serum concentrations of total and "free" insulin-like growth factor-I and on insulin-like growth factor binding protein patterns is reported. Sera were obtained from 20 patients with non-cirrhotic chronic liver diseases and from 20 patients with cirrhosis before and 24 h after a single subcutaneous dose of growth hormone. Samples were analyzed using radioimmunoassays, gel chromatography, ligand blotting and immunoblotting. In cirrhosis, serum concentrations of total and "free" insulin-like growth factor-I were decreased, the binding protein pattern was changed profoundly showing a reduction in the 150 kD complex and an increase in the 30-40 kD complexes. Concentrations of binding protein-1 and -2 were increased, while that of binding protein-3 was decreased in cirrhosis. The response to growth hormone was blunted. These changes were related to the degree of liver dysfunction as assessed by the Child-Pugh classification. A pathogenetic link of altered bio-availability of insulin-like growth factor-I to clinical characteristics of advanced liver disease, e.g. insulin resistance or skeletal muscle wasting, may be suggested by the present data.
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            Low doses of insulin-like growth factor-I improve nitrogen retention and food efficiency in rats with early cirrhosis

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              Changes in growth, growth hormone, and insulin-like growth factor-I (IGF-I) after orthotopic liver transplantation.

              Growth failure is an important consequence of chronic liver disease in childhood. Insulin-like growth factor-I (IGF-I), which is synthesized and released by the liver, plays an important role as a growth regulator in humans. We examined the growth hormone (GH)/IGF-I axis before and after orthotopic liver transplantation (LT) in 14 children aged between 2 and 11 years (mean 5.6 +/- 1.1 years). Pre-transplantation serum GH levels (7.5 +/- 1.2 ng/ml) were significantly higher (P < 0.001) compared with controls (5 +/- 0.5 ng/ml). However, post-transplantation levels (1.8 +/- 0.8 ng/ml) did not differ from those in the control group. Serum IGF-I levels showed a statistically significant increase after LT (20.1 +/- 9.4 vs 190 +/- 66.2 ng/ml; P < 0.001) and became indistinguishable from the levels in the control group (180 +/- 96 ng/ml). In comparison with pre-transplantation data (z - 2.70), there was an increase in height 4 years postoperatively (z - 1.68). Catch-up growth was highly significant, in particular during the 1st year after LT (z -1. 58 +/- 1.63 vs 2.59 +/- 5.29; P < 0.01). We conclude that a GH resistance state found in patients with severe chronic liver disease reverted following LT. Given that IGF-1 depends upon liver function, this could be one of the main factors in the significant catch-up growth in pediatric LT recipients.
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                Author and article information

                Journal
                HRE
                Horm Res Paediatr
                10.1159/issn.1663-2818
                Hormone Research in Paediatrics
                S. Karger AG
                1663-2818
                1663-2826
                2002
                2002
                15 May 2002
                : 57
                : 3-4
                : 105-112
                Affiliations
                aMedizinische Klinik II, Klinikum Grosshadern, Ludwig-Maximilians-Universität Munich; bMedizinische Klinik II, Universität Köln, Deutschland; cDSL Inc. and dDepartment of Pediatrics, Baylor College of Medicine, Houston, Tex., USA
                Article
                57960 Horm Res 2002;57:105–112
                10.1159/000057960
                12006706
                © 2002 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 4, References: 55, Pages: 8
                Categories
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