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. 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.