Hepatitis C Virus Coinfection May Be a Risk Factor for Atherosclerosis in HIV Positive Individuals

Cardiovascular disease has become a growing concern as effective antiretroviral therapy extends the lives of people with HIV. Studies have shown that HIV infection itself, as well as some of the drugs used to treat it, may increase the risk of heart disease. Coinfection with hepatitis C virus (HCV) may also play a role, according to a French study presented at the 44th Annual Meeting of the European Association for the Study of the Liver (EASL 2009) last month in Copenhagen.

The aim of the study was to evaluate the impact of HCV infection on the development of early atherosclerosis -- "hardening of the arteries" due to build up of plaques and inflammatory reactions -- in HIV positive individuals, and to look for an association between atherosclerosis and liver fibrosis.

A total of 18 HIV-HCV coinfected patients and 22 HIV positive individuals without hepatitis C were prospectively studied between December 2006 and January 2008. Early stage atherosclerosis was evaluated by measuring vascular intima-media thickness (IMT) -- thickness of the lining of blood vessel walls -- in the carotid (neck) and femoral (groin) arteries, as well as the presence of plaques using high-resolution ultrasound. Traditional cardiovascular risk factors, such as blood lipid levels, smoking, and family history, were also assessed. Liver fibrosis was indirectly estimated using blood biomarkers (hyaluronic acid, APRI score, FIB-4 index, FibroMeter) and transient elastometry (FibroScan).

Results

The prevalence of vascular plaques was 44% among HIV-HCV coinfected patients (7 carotid, 8 femoral) compared with 13% among HIV monoinfected participants (1 carotid, 4 femoral), a statistically significant difference (P = 0.04).

The median carotid IMT was 0.7mm in the coinfected patients versus 0.75 mm in the HIV monoinfected group.

In a multivariate regression analysis, the presence of vascular plaques was independently associated with HCV infection (odds ratio [OR] 10, or 10 times the risk; P= 0.018) and elevated blood cholesterol (OR 16; P = 0.008).

Coinfected patients with blood vessel plaques were considerably younger, on average, than HIV monoinfected individuals with plaques (47 vs 67 years; P = 0.018).

Levels of C-reactive protein, a blood marker of inflammation, was significantly elevated in patients with plaques (P = 0.046) and in those with metabolic syndrome (P = 0.005).

Estimated liver fibrosis was notably more pronounced in HIV-HCV coinfected patients compared with HIV monoinfected individuals based on several measures:

Median hyaluronic acid: 39.5 vs 19.5 mcg/mL;
APRI score: 0.53 vs 0.19;
FIB-4 score:1.53 vs 1.04;
FibroMeter score: 0.66 vs 0.23.
Transient elastometry: 7 vs 5 Kpa.

However, no significant correlations were identified between liver fibrosis/cirrhosis and early atherosclerosis markers.

"In this prospective study, in HIV patients, HCV infection as well as hypercholesterolemia were independently associated with early atherosclerosis," the investigators concluded.

This research adds another piece to the puzzle of the relationship between HIV and cardiovascular risk. Some recent studies, including the large SMART treatment interruption trial, indicate that ongoing HIV replication may lead to systemic inflammation -- even in the absence of advanced CD4 cell decline -- and the presence of an additional virus like HCV may compound the problem.

Based on their findings, the French investigators recommended that "more careful cardiovascular surveillance is therefore mandatory in HIV-HCV coinfected patients."

5/22/09

Cytokines and Inflammation Lab, University Hospital Antwerp Poitiers, Hepatology Unit, Cardiology Unit, Infectious Diseases Unit, University Hospital Poitiers, Poitiers, France.

Reference
C Silvain, M Wangermez, P Sosner, and others. Influence of Hepatitis C Virus (HCV) Infection on Atherosclerosis Risk in HIV-Infected Adults. 44th Annual Meeting of the European Association for the Study of the Liver (EASL 2009). Copenhagen, Denmark. April 22-26, 2009.

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