Chronic Hepatitis C Virus Infection, a New Cardiovascular Risk Factor?

Fanny Domont; Patrice Cacoub


Liver International. 2016;36(5):621-627. 

In This Article

HCV Infection and Carotid Atherosclerosis

Since 2002, Japanese studies have reported an association between HCV infection and an increased risk of carotid atherosclerosis (Table 1). HCV seropositivity is associated with an increased frequency of carotid atherosclerosis plaques, with an odds ratio (OR) of 1.92 [95% CI: 1.56–2.38] and an increased carotid intima-media thickness, OR 2.85 [2.28–3.57].[10,11] In multivariate analysis, the presence of HCV capsid proteins is an independent predictive factor of the presence of carotid plaques, OR 5.61 (95% CI: 2.06–15.26; P < 0.001). Another Japanese study, in 2003, found that in patients with HCV antibody and type 2 diabetes a statistically significant association between HCV and ultrasonographic evidence of carotid atherosclerosis.[16] Two Italian studies showed that HCV infection is predictive of increased carotid intima-media thickness.[17,18] Patients with non-alcoholic steatohepatitis (NASH), chronic hepatitis C (presence of anti-HCV antibodies and HCV RNA+) or chronic hepatitis B (HBs antigen, HBc antibodies and HBe antibodies, but negative for HBe antigen) showed a higher prevalence of carotid plaques compared to non-infected controls. Increased of carotid intima-media thickness was observed in the three groups of patients though not in the controls (r-value = 0.63, P < 0.001 for NASH; r-value = 0.44, P < 0.001 for HCV; r-value = 0.32, P < 0.05 for HBV). Therefore, NASH, HCV and hepatitis B (HBV) seem to be associated with the early occurrence of atherosclerosis independent of common cardiovascular risk factors, including insulin resistance and metabolic syndrome. Another study that focused on the presence of HCV RNA in carotid plaques suggests a local pro-atherogenic action of HCV. The prevalence of carotid atherosclerosis appears to be similar in patients with active hepatitis C (RNA+) or with a history of hepatitis C (RNA−),[19] with no influence of the viral replication on carotid atherosclerosis. Normalization of hepatic function after elimination of HCV results in improvement of the lipid abnormalities. An Italian working group demonstrated the importance of hepatic steatosis in the occurrence of atherosclerosis, particularly in patients with hepatitis C.[20] The prevalence of carotid atherosclerosis was greater in HCV-positive subjects with steatosis vs HCV-positive subjects without steatosis (26.0% vs 14.8%; P < 0.015). The prevalence of carotid atherosclerosis was also greater in HCV-positive patients with steatosis vs those with NASH (77.7% vs 57.8%; P < 0.0001). In multivariate analysis, steatosis related to HCV is an independent risk factor of carotid atherosclerosis, with an OR of 32.35 (95% CI: 5.4–230; P < 0.0001). Some studies have not found an association between HCV infection and carotid atherosclerosis, but they were done on cohorts with small sample sizes[21] and in patients with high cardiovascular risk like in haemodialysis patients.[22]

A spanish study, in a limited group of HCV/HIV co-infected patients (n = 70) demonstrated that HCV infection was associated with higher levels of sICAM-1 and sVCAM-1.[23] However, no evidence of increased subclinical atherosclerosis was found when endothelial function was evaluated through flow media dilatation, or when assessing the carotid intima-media thickness. An American study examined the relationship of HIV and hepatitis C virus with carotid artery intima-media thickness and the presence of carotid plaques in the Women's Interagency HIV Study. Hepatitis C virus infection was not associated with greater carotid artery intima-media thickness after adjustment for demographic and traditional cardiovascular risk factors.[24]

Chronic HCV infection seems to predispose patients to the development of atherosclerosis and leads to carotid plaques modifications,[25] although blood lipid levels and the prevalence of metabolic syndrome are lower in HCV-infected subjects. The mechanisms that are potentially involved include a chronic immunological challenge by HCV that results in an inflammatory response and in the production of pro-inflammatory cytokines.[26] Persistent infection disturbs the balance between immunostimulation and inhibitory cytokines, which could thus maintain a significant level of inflammation. The alteration in the cytokine balance observed in patients with chronic hepatitis C could result in these cardiovascular complications.[27] Otherwise, a recent Italian study has showed that severe hepatic fibrosis was independently linked to the presence of carotid plaques (OR 2.177, 95% CI: 1.043–4.542, P < 0.03).[28] In a recent cohort study from Taiwan, HCV-infected patients followed up for 13 years showed higher risk of developing peripheral arterial disease (HR 9.25; 95% CI: 6.35–13.5).[29] However, discordant results have been reported in a study on 233 HCV-seropositive patients and 4033 HCV-negative controls that did not find an independent association between HCV seropositivity and carotid intima-media thickness, carotid plaques and carotid stenoses.[30]