Objective: Insulin-like growth factor (IGF) I stimulates the proliferation of hepatic stellate cells (HSC), the primary source of extracellular matrix accumulation in liver fibrosis. In contrast, insulin-like growth factor binding protein (IGFBP) 3, the most abundant IGFBP in circulation, negatively modulates HSC mitogenesis. To investigate the role of the IGF axis in hepatitis C virus (HCV)-related liver disease among high-risk patients, we prospectively evaluated HCV-viremic/HIV-positive women.
Design: A cohort investigation.
Methods: Total IGF-I and IGFBP-3 were measured in baseline serum specimens obtained from 472 HCV-viremic/HIV-positive subjects enrolled in the Women's Interagency HIV Study, a large multi-institutional cohort. The aspartate aminotransferase to platelet ratio index (APRI), a marker of liver fibrosis, was assessed annually.
Results: Normal APRI levels (< 1.0) at baseline were detected in 374 of the 472 HCV-viremic/HIV-positive subjects tested, of whom 302 had complete liver function test data and were studied. IGF-I was positively associated [adjusted odds ratio comparing the highest and lowest quartiles (AORq4–q1), 5.83; 95% confidence interval (CI) 1.17–29.1; Ptrend = 0.03], and IGFBP-3 was inversely associated (AORq4–q1, 0.13; 95% CI 0.02–0.76; Ptrend = 0.04), with subsequent (incident) detection of an elevated APRI level (> 1.5), after adjustment for the CD4 T-cell count, alcohol consumption, and other risk factors.
Conclusion: High IGF-I may be associated with increased risk and high IGFBP-3 with reduced risk of liver disease among HCV-viremic/HIV-positive women.
From the aAlbert Einstein College of Medicine, Bronx, New York, USA
bUniversity of California San Francisco, San Francisco, California, USA
cYale University, New Haven, Connecticut, USA
dMaimonides Medical Center, Brooklyn, New York, USA
eCORE Center/Stroger Hospital of Cook County, Chicago, Illinois, USA
fGeorgetown University, Washington, DC, USA
gJohns Hopkins University, Baltimore, Maryland, USA
hUniversity of Southern California, Los Angeles, California, USA.
*See Acknowledgements for details of the Viruses and Hormones Study Group.
Received 24 July, 2007
Revised 4 September, 2007
Accepted 13 September, 2007
Correspondence to Howard D. Strickler, MD, MPH, Department of Epidemiology and Population Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Belfer 1308-B, Bronx, NY 10461, USA. E-mail: email@example.com