Hepatitis C Virus Infection, a New Modifiable Cardiovascular Risk Factor

Chronic hepatitis C virus (HCV) infection is a leading cause of liver-related morbidity and mortality worldwide. In addition, chronic HCV infection is considered a systemic infection with many extrahepatic manifestations that can lead to poor quality of life and major economic burden. Evidence of associations with stroke, coronary artery disease, peripheral arterial disease, and heart failure suggested that HCV infection might be a new cardiovascular (CV) risk factor.

Patients with HCV infection frequently have CV-associated risk factors such as diabetes, chronic kidney disease, or hypertension. However, it should be underlined that -- as for all diseases or events -- risk factors are rigorously defined by four types of evidence:

• Observational studies showing the presence of the factor before the event appearance
• Prospective translational or clinical studies demonstrating an increased prevalence rate of the factor in patients who will develop the event
• Mechanism of action studies
• Most importantly, outcome studies showing risk reduction when the putative factor is corrected

The study by Butt et al. ("Direct-acting Antiviral Therapy for HCV Infection is Associated with a Reduced Risk of Cardiovascular Disease Events") adds major information in this field. From a large cohort of HCV-infected veterans, they found that direct-acting agent (DAA) treatment was associated with a 43% reduction and pegylated interferon plus ribavirin (pegIFN/RBV) with a 22% reduction in risk of incident CV events compared with no treatment.

Treatment with DAAs was associated with lower event rates for all CV events compared with non-treated controls and those treated with a pegIFN/RBV. This publication was the missing part of the puzzle which now sustains the following assertion, the "factor" (HCV infection) is a new reversible independent risk factor for CV disease ("the event").

To summarize, the availability of safe and effective antiviral regimens that eradicate HCV infection in most patients, together with evidence that HCV infection is a reversible CV risk factor, reinforce some practical messages:

• All HCV-infected patients should have access to DAAs
• All HCV-infected patients should benefit from a complete CV check-up
• Liver, and more importantly, non-liver; physicians should be aware of the benefit of DAAs to improve liver and cardiovascular outcomes