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

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.