title: 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: a prospective study.
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 alpha-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 microg/L to 33.8 +/- 14.5 microg/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.
authors.affiliation: Department of Clinical and Experimental Medicine F. Magrassi, Second University of Naples, Naples, Italy.
authors.forename: Gherardo
authors.initials: G
authors.lastname: Mazziotti
authors.forename: Francesca
authors.initials: F
authors.lastname: Sorvillo
authors.forename: Filomena
authors.initials: F
authors.lastname: Morisco
authors.forename: Antonella
authors.initials: A
authors.lastname: Carbone
authors.forename: Mario
authors.initials: M
authors.lastname: Rotondi
authors.forename: Gianfranca
authors.initials: G
authors.lastname: Stornaiuolo
authors.forename: Davide F
authors.initials: DF
authors.lastname: Precone
authors.forename: Michele
authors.initials: M
authors.lastname: Cioffi
authors.forename: Giovanni B
authors.initials: GB
authors.lastname: Gaeta
authors.forename: Nicola
authors.initials: N
authors.lastname: Caporaso
authors.forename: Carlo
authors.initials: C
authors.lastname: Carella
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000821:virology; D005260:Female; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000821:virology*; D008113:Liver Neoplasms / Q000097:blood* / Q000821:virology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D012680:Sensitivity and Specificity; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D000509:alpha-Fetoproteins; D007334:Insulin-Like Growth Factor I