Successful hepatitis C treatment lowers risk of cardiovascular events

Treatment for hepatitis C, especially if it leads to a cure, is associated with a reduced risk of cardiovascular events such as congestive heart failure, heart attacks and strokes, according to research presented at IDWeek 2018 this month in San Francisco.

In a large study of US veterans, those treated with new direct-acting antivirals (DAAs) were about half as likely to experience cardiovascular events as untreated individuals (16 vs 30 events per 1000 person-years of follow-up, respectively).

Over years or decades, chronic hepatitis C virus (HCV) infection can lead to serious liver disease including cirrhosis, hepatocellular carcinoma and the need for a liver transplant. But HCV infection can have detrimental manifestations elsewhere in the body as well. The reasons for this are not full understood, as the virus itself primarily infects liver cells, but it could be related to chronic inflammation.

Several studies have found that people with hepatitis C are more prone to developing cardiovascular conditions such as coronary artery disease, peripheral vascular disease, myocardial infarction and stroke; however, other studies have not seen this association.

A growing body of evidence shows that HCV treatment can help reverse this increased risk. A recent study from France, for example, found that curing hepatitis C reduces the risk of cardiovascular events in people with compensated cirrhosis. But again, some large studies from the interferon era did not see a similar benefit.

It IDWeek, Prof Adeel Butt of Weill Cornell Medical College in New York presented findings from an analysis comparing the risk of new cardiovascular events among treated and untreated US veterans with hepatitis C in the ERCHIVES (Electronically Retrieved Cohort of HCV-Infected Veterans) database.

A previous ERCHIVES analysis by Butt's team, which included more than 82,000 veterans with hepatitis C and over 89,500 uninfected veterans, found that having HCV was independently associated with a 27% increase in the risk of coronary artery disease events.

In the new analysis, the researchers started with 242,680 veterans with chronic HCV infection. They excluded those with HIV or hepatitis B virus co-infection and those with pre-existing cardiovascular disease at baseline. Treated people were also excluded if they did not have HCV RNA measurements to determine whether they achieved sustained virological response (SVR), or undetectable viral load after completion of therapy, which is considered a cure.

The final population included 4436 people treated with pegylated interferon plus ribavirin and the same number of matched control subjects who never received treatment, as well as 12,667 people treated with DAAs, again with the same number of matched untreated controls. People who had been treated on separate occasions with both pegylated interferon/ribavirin and DAAs were excluded. Across all treated people, the overall SVR rate was 76%.

In both groups, most participants (96%) were men, over half were white, about a quarter were African American and the median age was approximately 58 years. Cardiovascular risk factors were common, including current or past smoking (66%), obesity (32%), high blood pressure (53%), diabetes (about 9%) and use of statins (24%).

The study looked at new cardiovascular events occurring at least 12 weeks after the start of HCV treatment: acute myocardial infarction, stroke, unstable angina (chest pain indicating inadequate blood reaching the heart muscle), congestive heart failure, peripheral vascular disease and the need for coronary angioplasty or coronary artery bypass procedures.

After adjusting for cardiovascular risk factors, the incidence of cardiovascular events was 30.4 per 1000 person-years among untreated individuals, compared with 20.8 per 1000 person-years among those who received treatment (p < 0.0001).

Breaking this down by type of treatment, the incidence rates were 23.5 and 16.3 per 1000 person-years, respectively, for those treated with pegylated interferon/ribavirin and DAAs (p < 0.0001). Combing both types of treatment, cardiovascular events occurred in 19.1 per 1000 people who achieved SVR and 22.5 per 1000 who were not cured (p < 0.0001).

Over 30 months of follow-up, treated individuals had a significantly longer duration of survival without cardiovascular events.

Based on these findings, Butt and colleagues concluded, "HCV treatment is associated with a significantly reduced risk of cardiovascular events. Those treated with a DAA regimen and those who achieve SVR have a greater benefit."