Insulin Resistance Is Associated With Progression to Hepatic Fibrosis in a Cohort of HIV/Hepatitis C Virus-Coinfected Patients

Mark W. Hull; Kathleen Rollet; Erica E.M. Moodie; Sharon Walmsley; Joseph Cox; Martin Potter; Curtis Cooper; Neora Pick; Sahar Saeed; Marina B. Klein

Disclosures

AIDS. 2012;26(14):1789-1794. 

In This Article

Abstract and Introduction

Abstract

Objective: Hepatitis C virus (HCV) infection is associated with higher insulin levels and insulin resistance. We evaluated factors associated with insulin resistance in a cohort of HIV/HCV-coinfected patients and determined the effect of insulin resistance on the development of hepatic fibrosis.
Methods: Data were analysed from 158 nondiabetic participants in a prospective Canadian cohort of HIV/HCV-coinfected patients. Patients were defined as having insulin resistance using the homeostasis model for assessment of insulin resistance (HOMA-IR) index. Factors associated with a high index (HOMA-IR ≥2) were identified using multivariate logistic regression. Incidence rates of liver fibrosis [aspartate aminotransferase-to-platelet ratio index (APRI) ≥1.5] were calculated, and multivariate time-dependent Cox regression models used to assess the effect of baseline insulin resistance on the risk of developing an APRI score of at least 1.5 during follow-up.
Results: Overall, 56% had baseline HOMA-IR of at least 2. In the adjusted multivariate logistic analysis, only baseline BMI of more than 25 kg/m2 remained associated with insulin resistance [adjusted odds ratio 3.66, 95% confidence interval (CI) 1.70–7.92]. Rates of progression to significant hepatic fibrosis (APRI ≥1.5) were higher in those with HOMA-IR of at least 2 (16.32 per 100 person-years, 95% CI 6.68–25.97) compared with those with HOMA-IR less than 2 (7.95 per 100 person-years, 95% CI 0.16–15.75). Baseline HOMA-IR of at least 2 was associated with the development of significant fibrosis (adjusted hazard ratio 7.71, 95% CI 2.55–23.36).
Conclusion: In this first longitudinal analysis, insulin resistance was very common among coinfected patients and was associated with modifiable risk factors such as elevated BMI. Insulin resistance was found to be strongly associated with progression to hepatic fibrosis over time.

Introduction

Hepatitis C virus (HCV) infection has been associated with an increased risk for insulin resistance and diabetes[1] with 30–70% exhibiting some degree of insulin resistance.[2] Insulin resistance has been associated with a wide variety of adverse health outcomes such as cardiovascular disease and cancer and with decreased response to HCV therapy among HCV-monoinfected patients.[3–6] The homeostasis model for assessment of insulin resistance (HOMA-IR) index is a well validated noninvasive method to measure insulin sensitivity.[7] HCV-infected individuals have been shown to have higher HOMA-IR scores (compared with uninfected matched controls)[1] which have been associated with fibrosis and steatosis in cross-sectional analyses.[8] In HIV-infected patients, HCV has also been shown to be associated with the presence of insulin resistance,[9–11] but its association with progressive fibrosis is less clear.[12] We evaluated factors associated with insulin resistance in a cohort of HIV/HCV-coinfected patients and determined the impact of insulin resistance on the development of liver fibrosis prospectively.

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