How non-alcoholic fatty liver disease increases risk of vascular diseases

These findings by scientists shed light on why the leading cause of mortality in NAFLD patients is cardiovascular complications, instead of liver damage.  

NAFLD is a general term for liver diseases affecting patients who drink little to no alcohol. It is mainly characterised by having too much fat stored in liver cells and can lead to liver cirrhosis and liver cancer.

 It is estimated that up to 40 per cent of the population in Southeast Asian countries, including Singapore, have NAFLD.

 The research team found a higher level of blood vessel damage in NAFLD patients, which increases the risks of blood clots and cardiovascular diseases.

The team recreated blood vessel cells from samples donated by 99 NAFLD patients and 56 healthy controls to be used as experimental models for the study.

They found that the blood vessel cells of fatty liver disease patients contained higher levels of a class of proteins called chemokines – up to three times higher than in healthy individuals.

Chemokines are strong attractants of immune cells. Their main role in the body is drawing immune cells to sites of infections so that these cells can combat infections. However, when abnormally high levels of immune cells are recruited into a blood vessel, it becomes harmful.

In particular, the researchers noticed that a type of immune cells known as T cells were strongly responsive to the chemokines in NAFLD patients. T cells are an important part of the body’s immune system that fight against foreign particles.

 The researchers discovered that the higher level of chemokines in fatty liver disease patients was attracting T cells into blood vessel walls. These T cells then caused inflammation of blood vessels, damaging them.

 Higher levels of damage and inflammation can lead to leakiness in the blood vessels, impairing blood vessels’ integrity over time and increasing the risk of blood clot formation. It can lead to devastating events if the blood flow to vital organs is obstructed, such as ischaemic tissue injury.

 The team detected three times as many circulating damaged endothelial cells — cells from the inner lining of blood vessels that have been shed into the bloodstream — in fatty liver disease patients, which is a sign of blood vessel injury.

 The researchers believe that fatty liver disease patients have increased chemokine production due to the higher levels of oxidized lipids and free fatty acids in their blood.

The paper’s first author said: “Blood vessels are likely to be sensitive to the inflammatory mediators and abnormal lipid metabolism which underlie non-alcoholic fatty liver disease. We discovered that non-alcoholic fatty liver disease blood vessel cells are more ‘activated’, making them susceptible to vascular inflammation.” 

Understanding how NAFLD affects heart health should help to inform clinical care for patients, the researchers say.

Typically, patients who present with symptoms of fatty liver diseases are not commonly referred to cardiologists. However, as the team’s research has shown that chronic inflammation and damage to blood vessels can lead to heart disease, it might be prudent for a patient’s vascular health to be monitored as well.

The senior author said: “As we better understand the link between non-alcoholic fatty liver disease and vascular inflammation, the science helps to inform clinical care. Patients who seek medical treatment for liver disease, for instance, could be considered for vascular health check-ups. This way, doctors not only follow up on the liver health but potentially prevent vascular complications in the future.”

 “Liver disease at its early stage is reversible with lifestyle changes such as exercise and a healthy diet. Lifestyle modification is key at an early stage to slow down the progression of both fatty liver disease and cardiovascular disease before they become too advanced for functional recovery,” added the author.