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The insulin-like growth factor axis and risk of liver disease in hepatitis C virus/HIV-co-infected women

Strickler, Howard Da; Howard, Andrea Aa; Peters, Marionb; Fazzari, Melissaa; Yu, Herbertc; Augenbraun, Michaeld; French, Audrey Le; Young, Maryf; Gange, Stepheng; Anastos, Kathryna; Kovacs, Andreah,*

doi: 10.1097/QAD.0b013e3282f22cdf
Epidemiology and Social: Concise Communication

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:

© 2008 Lippincott Williams & Wilkins, Inc.