Prognostic value of insulinlike growth factor I and its binding protein in patients with alcohol-induced liver disease

Abstract

Insulinlike growth factor I (IGF-I) is a single-polypeptide chain with important anabolic and endocrine activities. The liver is the major source of IGF-I and its binding protein, IGFBP-3. Circulating concentrations of IGF-I and IGFBP-3 are decreased in patients with chronic liver disease and correlate with the severity. The aim of this study was to assess the additional prognostic value of IGF-I and IGFBP-3 in patients entered in a large multicenter study (EMALD). Three hundred thirty-seven patients with alcohol-induced liver disease were studied in a randomized placebo-controlled trial of malotilate with a mean follow-up period of 569 days (range, 7- 1,544). A multivariate Cox regression analysis of pertinent clinical and biochemical variables showed a significant independent prognostic value of years of alcohol intake, coagulation factors 2, 7, and 10, alkaline phosphatases, serum creatinine, and immunoglobulin (Ig) M. When IGF-I or IGFBP-3 were added into this model, a Cox regression analysis showed that either had a significant independent prognostic value. Because IGF-I and IGFBP-3 were closely correlated, they contained almost the same prognostic information. Inclusion of IGF-I gave these results: IGF-I (P < .03), alcohol intake (P < .02), coagulation factors 2, 7, and 10 (P < .01), creatinine (P < .001), and IgM (P < .01) contained independent prognostic information. Inclusion of IGFBP-3 gave these results: IGFBP-3 (P < .02), alcohol intake (P < .05), coagulation factors 2, 7, 10 (P < .01), creatinine (P < .001), and IgM (P < .02) were independent predictors of survival. In conclusion, IGF-I or IGFBP-3 provide important additional information on survival in patients with alcohol-induced liver disease.