The insulin-like growth factor binding protein 3 ternary complex is reduced in cirrhosis.

ABSTRACT

BACKGROUND/AIMS: In healthy adults, serum insulin-like growth factor I (IGF-I), IGF binding protein 3 (IGFBP-3) and acid labile subunit (ALS) form a 150-kDa ternary complex under the control of growth hormone (GH). Approximately 80-90% of circulating IGF-I is bound to the ternary complex. In cirrhosis the GH/IGF axis is severely disturbed and the individual components of the ternary complex are reduced. However, the degree of ternary complex formation in cirrhosis has not previously been described. METHODS: Serum IGF-I, IGFBP-3, ALS, the 150-kDa ternary complex and IGFBP-3 proteolysis were all measured in six compensated and six decompensated cirrhotic patients and compared to six healthy controls. RESULTS: Patients with compensated cirrhosis had decreased levels of IGF-I (55%), IGFBP-3 (64%) and ALS (53%), and in the decompensated patients these levels were decreased even further IGF-I (32%), IGFBP-3 (37%) and ALS (27%) compared to healthy controls. The levels of the ternary complex followed this pattern, with low levels seen in the compensated patients (66%) and a further reduction in the decompensated patients (27%). Ternary complex levels correlated negatively with the Child-Pugh score. No increase in IGFBP-3 proteolysis was found in cirrhotic patients compared to healthy controls. CONCLUSION: Cirrhosis is associated with reduced levels of the 150-kDa ternary IGFBP-3 complex correlating with the degree of liver disease.