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

Howard Strickler, Andrea A. Howard, Marion Peters, Melissa Fazzari, Herbert Yu, Michael Augenbraun, Audrey L. French, Mary Young, Stephen Gange, Kathryn Anastos, Andrea Kovacs

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)527-531
Number of pages5
JournalAIDS
Volume22
Issue number4
DOIs
StatePublished - Feb 2008

Fingerprint

Somatomedins
Hepacivirus
Insulin-Like Growth Factor Binding Protein 3
Liver Diseases
Insulin-Like Growth Factor I
HIV
Hepatic Stellate Cells
Liver Cirrhosis
Blood Platelets
Insulin-Like Growth Factor Binding Proteins
CD4 Lymphocyte Count
Aspartate Aminotransferases
Transaminases
Alcohol Drinking
Extracellular Matrix
T-Lymphocytes
Serum

Keywords

  • APRI
  • Aspartate aminotransferase to platelet ratio index
  • Hepatitis C virus (HCV)
  • HIV
  • IGF
  • IGFBP-3
  • Liver disease

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

The insulin-like growth factor axis and risk of liver disease in hepatitis C virus/HIV-co-infected women. / Strickler, Howard; Howard, Andrea A.; Peters, Marion; Fazzari, Melissa; Yu, Herbert; Augenbraun, Michael; French, Audrey L.; Young, Mary; Gange, Stephen; Anastos, Kathryn; Kovacs, Andrea.

In: AIDS, Vol. 22, No. 4, 02.2008, p. 527-531.

Research output: Contribution to journalArticle

Strickler, H, Howard, AA, Peters, M, Fazzari, M, Yu, H, Augenbraun, M, French, AL, Young, M, Gange, S, Anastos, K & Kovacs, A 2008, 'The insulin-like growth factor axis and risk of liver disease in hepatitis C virus/HIV-co-infected women', AIDS, vol. 22, no. 4, pp. 527-531. https://doi.org/10.1097/QAD.0b013e3282f22cdf
Strickler, Howard ; Howard, Andrea A. ; Peters, Marion ; Fazzari, Melissa ; Yu, Herbert ; Augenbraun, Michael ; French, Audrey L. ; Young, Mary ; Gange, Stephen ; Anastos, Kathryn ; Kovacs, Andrea. / The insulin-like growth factor axis and risk of liver disease in hepatitis C virus/HIV-co-infected women. In: AIDS. 2008 ; Vol. 22, No. 4. pp. 527-531.
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abstract = "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.",
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AU - Howard, Andrea A.

AU - Peters, Marion

AU - Fazzari, Melissa

AU - Yu, Herbert

AU - Augenbraun, Michael

AU - French, Audrey L.

AU - Young, Mary

AU - Gange, Stephen

AU - Anastos, Kathryn

AU - Kovacs, Andrea

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N2 - 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.

AB - 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.

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KW - HIV

KW - IGF

KW - IGFBP-3

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