Successful hepatitis C virus (HCV) therapy reduces the risk of a serious cardiovascular event in people with compensated liver cirrhosis, French investigators report in the American Heart Journal. A sustained virological response (SVR) was associated with a 65% reduction in the risk of a major adverse cardiovascular event such as stroke and heart attack.
“We found (1) that the main independent predictive factors of MACE [major adverse cardiovascular event] occurrence were Asian ethnic origin, arterial hypertension, and low serum albumin and (2) that an SVR was associated with a decreased risk of MACE,” comment the authors. “Further studies are warranted to evaluate whether a similar benefit can be obtained in less severe patients, such as noncirrhotic HCV-infected patients.”
The World Health Organization estimates that up to 170 million people worldwide have HCV. If left untreated, HCV can cause cirrhosis and liver cancer, in many cases leading to death. The infection has also been associated with a number of serious non-liver-related complications, including cardiovascular disease. The reasons for this are poorly understood, but could include colonization of arteries by HCV and the inflammatory effects of the virus.
A protein made in the liver, needed to maintain a balance of the fluids in the body. In a blood test, lower than normal levels of albumin and total protein may indicate liver damage or disease. If there is not enough albumin, fluid may accumulate in the abdomen (ascites).
- compensated cirrhosis
The earlier stage of
cirrhosis, during which the liver is damaged but still able to perform most of
its functions. See also ‘cirrhosis’ and ‘decompensated cirrhosis’.
- sustained virological response (SVR)
Undetectable hepatitis C RNA after treatment has come to an end. Usually SVR refers to RNA remaining undetectable for 24 weeks (six months) after ending treatment and is considered to be a cure. SVR4 and SVR12 refer to RNA remaining undetectable for 4 and 12 weeks respectively.
HCV therapy that achieves SVR – an undetectable HCV viral load 12 weeks after the completion of treatment – has been associated with a decreased risk of death due to serious liver disease. There is also some evidence that it also lowers non-liver-related mortality risk.
Investigators from the French CirVir cohort collaboration wanted to see if SVR reduced the risk of a major cardiovascular event in people with HCV-related cirrhosis.
They therefore designed a prospective study involving people who received HCV therapy between 2006 and 2012. Data were gathered on HCV treatment outcomes and the incidence of serious cardiovascular events including stroke, myocardial infarction, ischemic heart disease, heart failure, peripheral arterial disease, cardiac arrest and cardiovascular death. The investigators calculated the beneficial effects of SVR on cardiovascular risk and the impact of a major cardiac event on five-year survival rates.
The study population consisted of 878 adults, all of whom had biopsy-proven compensated cirrhosis. People with HIV or hepatitis B virus co-infection were excluded.
Study participants received a variety of HCV regimens, though most (n = 587) were treated with pegylated interferon and ribavirin.
The median duration of follow-up was 58 months, during which a major cardiac event was diagnosed in 7% of people.
After controlling for potential confounders, factors associated with an increased risk of a serious cardiovascular event were arterial hypertension (p < 0.001), smoking (p < 0.001), Asian ethnicity (p = 0.03) and low serum albumin (p = 0.009).
A major cardiac event was observed in 1% of people who attained an SVR compared to 10% of non-SVR patients.
Overall, SVR reduced the risk of a major cardiovascular outcome by 65% (HR = 0.35; 95% CI, 0.009-0.97; p = 0.044). There was some evidence that SVR using interferon-free therapies were associated with the greatest reduction in cardiovascular risk, but the finding fell short of statistical significance.
There were 138 deaths during follow-up, including 35% of people with a major cardiovascular event compared to 14% of people who did not experience significant cardiovascular disease (difference, p < 0.001). The five-year survival rate was significantly higher among people who did not have a major cardiovascular event compared to those who did (86% vs 60%, p < 0.001).
“MACE occurrence in patients with compensated HCV cirrhosis is influenced by constitutional features (Asian ethnic origin), cardiovascular risk factors (arterial hypertension), and the severity of liver disease (low serum albumin),” conclude the authors. “This risk can be modulated through eradication of HCV, as an SVR is associated with a decreased rate of MACEs. Such results strengthen the systematic nature of HCV infection, a chronic disease in which cardiovascular risk must be carefully assessed. The decreased rate of MACEs after SVR in this population should be taken into account to enable wider access to new DAAs.”