Back HCV Disease Progression Fibrosis/Cirrhosis Insulin Resistance Linked to Liver Disease Progression in HIV/HCV Coinfected Patients

Insulin Resistance Linked to Liver Disease Progression in HIV/HCV Coinfected Patients

alt

Insulin resistance is common among HIV positive people with hepatitis C virus (HCV) coinfection and is strongly associated with progression to liver fibrosis over time, Canadian researchers reported in the June 27, 2012, advance online edition of AIDS.

Prior studies have shown that people with HCV infection tend to have higher insulin levels and a greater degree of insulin resistance, meaning cells do not respond normally to insulin. Insulin resistance can progress to diabetes, and high blood sugar contributes to cardiovascular disease and a host of other problems. HIV infection and antiretroviral therapy (ART) have also been linked to insulin resistance in some studies, but data are less consistent.

Mark Hull from the Centre for Excellence in HIV/AIDS at the University of British Columbia and fellow investigators looked at factors associated with insulin resistance in a cohort of HIV/HCV coinfected patients and assessed the effect of insulin resistance on development of liver fibrosis.

The analysis included 158 non-diabetic patients in the prospective Canadian Co-infection Cohort Study. Nearly two-thirds were men, the median age was 45 years, 23% had a history of recent injection drug use, and most (89%) were on combination ART.

The researchers determined insulin resistance using the homeostasis model for assessment of insulin resistance (HOMA-IR) index -- with scores of > 2 considered high -- and evaluated the link between baseline insulin resistance aon the risk of developing significant liver fibrosis with a score of > 1.5 on the APRI biomarker index.

Results

  • Overall, 56% of study participants had baseline HOMA-IR scores > 2, including 27% with scores >4.
  • In an adjusted multivariate analysis, only baseline body mass index >  25 (the cut-off for being considered overweight) remained associated with insulin resistance (adjusted odds ratio 3.66, or more that 3 times higher risk).
  • There was no observed association between use of specific antiretroviral drugs and insulin resistance at baseline.
  • 18% of participants developed significant fibrosis during a median follow-up period of 1.4 years.
  • The likelihood of progression to significant fibrosis was about twice as high for people with HOMA-IR > 2 vs < 2 (16.32 vs 7.95 per 100 person-years, respectively).
  • Baseline HOMA-IR > 2 was independently associated with development of significant fibrosis, with an adjusted hazard ratio of 7.71, or nearly 8-fold higher risk.
  • For each doubling of HOMA-IR score, the risk of progression to fibrosis increased by 48%.

"In this first longitudinal analysis, insulin resistance was very common among coinfected patients and was associated with modifiable risk factors such as elevated body mass index," the study authors concluded. "Insulin resistance was found to be strongly associated with progression to hepatic fibrosis over time."

"Mechanisms by which insulin resistance occur in HCV-infected patients have not been fully elucidated, but include effects of inflammatory cytokines such as TNF-alpha, other cytokine signaling pathways (e.g. upregulation of suppressor of cytokine signaling-3 protein) and effects on insulin-receptor substrate which interferes with insulin signaling," they explained in their discussion. "Whether HIV directly plays a role remains unclear."

"Given the very high prevalence of insulin resistance, its known association with important health outcomes and its associated high risk for liver disease progression observed in this study, routine screening for insulin resistance among coinfected persons may be warranted," they recommended. "Interventional studies to manage modifiable risk factors for insulin resistance and evaluate the role of pharmacotherapy in modifying the course of liver disease progression and improving HCV treatment outcomes among HIV/HCV coinfected persons are needed."

7/13/12

Reference

MW Hull, K Rollet, EE Moodie, et al (Canadian Co-infection Cohort Study Investigators. Insulin resistance is associated with progression to hepatic fibrosis in a cohort of HIV/HCV co-infected patients. AIDS. June 27, 2012 (Epub ahead of print).