Serum insulin‐like growth factor I evaluation as a useful tool for predicting the risk of developing hepatocellular carcinoma in patients with hepatitis C virus‐related cirrhosis

Abstract

BACKGROUND Although experimental studies have demonstrated an important role of insulin‐like growth factor I (IGF‐I) in hepatocarcinogenesis, the clinical data about IGF‐I in patients with hepatocellular carcinoma (HCC) are scarce and controversial. To the authors' knowledge, this is the first prospective study investigating the longitudinal correlation between modifications in serum IGF‐I levels and the development of HCC in a cohort of patients with hepatitis C virus (HCV)‐related cirrhosis. METHODS One hundred fourteen consecutive patients with HCV‐related Child Grade A cirrhosis were followed prospectively at the Second University of Naples for 56.4 ± 12.0 months with ultrasound examinations of the liver and serum α‐fetoprotein determination every 6 months. At each clinical evaluation, the severity of disease was graded according to the established Child–Pugh scoring system. Serum IGF‐I levels were measured prospectively at the study entry and at least every 12 months throughout follow‐up. RESULTS Twenty patients (19.2%) developed HCC during follow‐up. Eleven of these patients had persistent Child Grade A cirrhosis for the whole study, whereas the other 9 patients developed HCC after their cirrhosis progressed from Child Grade A to Grade B. In patients who remained free of HCC for the whole study, serum IGF‐I concentrations did not modify significantly during follow‐up. Conversely, in patients who developed HCC, IGF‐I levels decreased significantly during follow‐up (from 72.6 ± 29.9 μg/L to 33.8 ± 14.5 μg/L; P = 0.001). In these patients, the significant decrease occurred both in patients with persistent Child Grade A cirrhosis and in patients with cirrhosis that progressed from Child Grade A to Grade B. The reduction in IGF‐I level preceded the diagnosis of HCC by 9.3 ± 3.1 months. CONCLUSIONS This prospective study demonstrates that, in patients with HCV‐related cirrhosis, 1) the development of HCC is accompanied by a significant reduction of serum IGF‐I levels independent of the grade of impairment of liver function; and 2) modification of the IGF‐I level precedes the morphologic appearance of HCC, permitting a precocious diagnosis of the tumor. Cancer 2002;95:2539–45. © 2002 American Cancer Society. DOI 10.1002/cncr.11002