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


METHODS
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.


CONCLUSIONS
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.
Strickler
Howard D
HD
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York 10461, USA. strickle@aecom.yu.edu
Howard
Andrea A
AA
Peters
Marion
M
Fazzari
Melissa
M
Yu
Herbert
H
Augenbraun
Michael
M
French
Audrey L
AL
Young
Mary
M
Gange
Stephen
S
Anastos
Kathryn
K
Kovacs
Andrea
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D001219:Aspartate Aminotransferases / Q000378:metabolism; D004812:Epidemiologic Methods; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000201:enzymology; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000201:enzymology; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000201:enzymology / Q000821:virology*; D008875:Middle Aged; D014481:United States / Q000453:epidemiology; D014766:Viremia / Q000453:epidemiology
D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D001219:Aspartate Aminotransferases