NAFLD index

How does fatty liver disease develop?

We know fatty liver, for example, from goose liver that is eaten as 'foie gras'. The animals are forced to eat in an unhealthy way, which causes them to develop fatty liver. In humans, an unhealthy lifestyle without excessive alcohol consumption leads to non-alcoholic fatty liver disease, abbreviated as NAFLD.

In addition to lifestyle, fatty liver also has several other causes. The most important factors that play a role are the use of alcohol, drinking a lot of fructose-sweetened drinks (such as Cola) and medicines such as prednisone. Much research has been done into the cause of non-alcoholic fatty liver disease (NAFLD). The main cause of NAFLD is an unhealthy lifestyle. That means eating too many unhealthy foods with calories that are not consumed by activities such as exercise. This results in overweight and obesity in most people, with too much fat being stored in different places in the body. Those places are under the skin, but mainly in the abdomen and also in the liver.

Fat is a very good and efficient way to store energy for bad times. Unfortunately, too much fat is bad for our body. At a certain point, the body indicates that enough has been stored by, among other things, reducing its sensitivity to insulin (the hormone that regulates blood sugar). This changes the sugar and fat balance and ultimately leads to severe insulin insensitivity, which can eventually lead to diabetes. It is too simple to think that lifestyle alone is responsible. Hereditary susceptibility, the intestinal bacteria, the use of medicines, drugs and alcohol, a chronic liver disease due to, for example, a virus infection (hepatitis B or C) are factors that can contribute to a chronic liver inflammation.

The different stages of fatty liver disease

Fatty liver usually develops slowly over several years at the same time as being overweight and obese. In 30% of people with fatty liver, chronic liver inflammation develops over time, resulting in scarring. Without intervention, more and more scar tissue accumulates, which ultimately leads to a scarred liver (liver cirrhosis).

Figure: standard liver biopsy. The white areas are the cells where fat was stored. The cells indicated by the arrow are the cells that have come to the liver to clean up damaged cells and are part of the inflammatory response.

The probably harmless fatty liver (NAFLD) can easily be treated with a weight loss of at least 5% through lifestyle adjustments. When there is a chronic inflammation called non-alcoholic steato-hepatitis or NASH for short, it is important to know whether and how much scar tissue (fibrosis) is present. This is a very important factor in determining the severity of the disease. The degree of inflammation can currently only be determined with a liver biopsy (see figure above). The degree of fibrosis can also be determined with blood tests and other research methods such as the FibroScan which measures elasticity as a measure of the amount of scar tissue.

Figure: the different stages of non-alcoholic fatty liver disease.

So the chronic liver inflammation, which persists for years, is what causes the formation of scar tissue called fibrosis, which can eventually lead to liver cirrhosis. This inflammation also makes the liver more susceptible to developing cancer. This chance is much higher when cirrhosis has already developed, but is also increasingly seen in NAFLD without severe scarring (see figure above).

How do you know you have fatty liver disease?

In the beginning, fatty liver does not cause any complaints and is often found by chance because an abdominal ultrasound is made. Blood tests can also show slight abnormalities of the liver values that could be associated with fatty liver.

There are no specific liver complaints that are consistent with fatty acids. The liver adapts by enlarging so that all functions are preserved. Because the abdomen also enlarges more often, it is difficult for the doctor to determine that the liver volume has increased. Vague complaints such as fatigue, the feeling of having less energy and stamina, a feeling of fullness or pressure in the right upper abdomen can occur, but are not very specific and also occur in many other diseases.

What is NASH?

Non-alcoholic steato-hepatitis (NASH) is a chronic inflammation of the liver that occurs in three in ten people with long-term fatty liver disease. The liver cells, as it were, slowly succumb to the large amounts of fat that they can no longer process. This causes a disturbance in the metabolism of the cell. This leads to exhaustion of the cell functions, which can cause the liver cell to die. Inflammatory cells signal that cells are damaged or dead and come to clear them up. If this normal process takes place extensively, the liver becomes inflamed and the body responds by sending more clearing cells to this area, causing the inflammation to spread throughout the liver. This is a normal immune response that creates scar tissue that disappears in the liver after the inflammation has stopped. With prolonged inflammation such as in NASH, this can lead to fibrosis and cirrhosis. It is not yet entirely clear why someone develops liver inflammation because there are many factors that influence each other in the long run.

The main factors that play a role are:

Aging causing a decrease in body flexibility
Hereditary susceptibility
Overweight and obesity
Type 2 diabetes
Use of many drugs
Chronic inflammation
Use of alcohol and drugs
Too much unhealthy food
Consumption of many sweetened drinks (fructose)
Too little exercise
Altered composition of the gut bacteria
Production of bad fats and breakdown substances
Too few protective substances such as vitamin C and antioxidants

What could be long term consequences?

The chronic inflammation that is present in NASH can cause liver scarring with eventual liver cirrhosis and increased risk of liver cancer. A liver transplant is the only solution to achieve a cure in the case of liver cirrhosis and liver cancer. In a large number of patients, fatty liver comes back after transplantation if they do not change their lifestyle.

Scarring and livercirrhosis
‍Over time, the inflammation in the liver causes scar tissue to form, comparable to a wound on the skin. After the scab has fallen off, there is a slightly swollen pink line that later becomes smaller and white because the tissue contracts. This also occurs in the liver, which shrinks as the scar tissue contracts. This is called liver cirrhosis and is what causes liver functions to deteriorate. Over time, this leads to complications such as an abdomen full of fluid (ascites), varicose veins in the esophagus (varices), with a risk of spontaneous bleeding, and accumulation of toxic substances such as ammonia that can cause confusion. This occurs in approximately 10 to 20% of individuals with chronic liver inflammation. It is expected that in a few years liver cirrhosis due to NAFLD and in particular NASH will be the main cause for liver transplants.

Livercancer
Research has shown that individuals with NAFLD have a greater risk of developing liver cancer. This does not only apply to the advanced stage of liver disease or liver cirrhosis, but can develop earlier. For example, it can occur in NASH that has been around for a long time due to the combination of chronic inflammation and metabolic alteration. Worldwide, liver cancer or in medical terms hepatocellular carcinoma (HCC) is the fifth most common malignant cancer. Men are about two to three times more likely to be at risk than women.

What are the consequences for the rest of the body?

The liver has an important function for maintaining the healthy functioning of many organs (see: what does the liver do). The function of the liver is vital to good health.

Due to the many factors that influence the development of fatty liver, the search for effective medicines is slow. Research has shown that being older than 50, having diabetes, and being overweight and obese are the main risk factors for developing liver inflammation. In addition, fatty liver with inflammation poses a higher risk of developing and worsening diabetes, cardiovascular disease and various cancers, including liver cancer.

However, most patients with liver inflammation and scarring die from cardiovascular disease, complications of diabetes and have a greater chance of developing various malignant diseases such as colon cancer, than average. This shows that the liver plays a crucial role in health.

‍A healthy liver is a healthy life.

What is the prognosis?

Fatty liver (NAFLD) and NASH can fully recover, mainly through lifestyle changes so that liver fat decreases, which is accompanied by a decrease in body weight. If cirrhosis and/or liver cancer has developed, the prognosis is less good and medical treatments are necessary.

As long as the liver is in the stage of fatty liver or inflammation, the warning light is orange and, if detected and treated in time, the liver can still fully recover. In concrete terms, this means that fatty liver is reversible in most people. Studies have shown that with 5% weight loss the fatty liver decreases, with 7-10% also inflammation and scar tissue formation. That is, weight reduction is the cornerstone for the treatment of NAFLD.
‍
Individuals with only fatty liver have a low risk of dying from liver disease. But if the inflammation persists, there is a high risk of developing liver cirrhosis and liver cancer. Then a liver transplant is the only option to cure. However, fatty liver can easily come back after transplantation and develop into a more severe form much more quickly.

The effects on other organs involved in NAFLD also respond favorably to a decrease in fatty liver and inflammation. This means that when the liver functions are properly restored, the functioning of the involved organs will also improve and/or recover.

What is the treatment?

Currently, no drug is registered for the treatment of NAFLD. This is because many factors play a role in the development and course of fatty liver. Lifestyle adjustment is the most important step in therapy. This is not easy because changing a habit is very difficult.

A large number of factors can be identified that play a role in the development or worsening of fatty liver. In general, we refer to this as lifestyle and the change in lifestyle adjustment. To get an idea of which lifestyle factors play a role, you can ask yourself a number of questions as indicated below. This will give you a better understanding of the points that are important to you:

What is your diet; how often do you eat, what do you eat, do you snack, do you use snacks?
Do you drink a lot of sweetened drinks and alcohol regularly?
To move; how much exercise do you have in a day, a week?
Do you have daily bowel movements or is it difficult?
Do you come from a family with a susceptibility to becoming overweight?
Are you in the menopause and do you notice that your body is changing and it is more difficult to lose weight?
Do you have a lot of stress and do you react to this by eating more or taking snacks?
Do you have a bad night's sleep, do you snore a lot and does your breathing sometimes stop?
Are you taking any medications that could make fatty liver disease worse?
Do you have a lot of psychological problems, loneliness, sadness?

n other words, from the points mentioned you can see that many aspects can play a role. It is understandable that you cannot change all aspects directly. Over the years, habits have developed that together form your lifestyle. And as mentioned, changing a habit takes a lot of energy. The most important thing in this is to face the points to be changed, in other words awareness. This is the first step. Then you can make a choice for yourself what you want to pay attention to in the first place to change this. It is wise to choose something simple.

When you have achieved this, it gives a good feeling and gives you self-confidence. After that you can focus on other aspects. When it comes to more complex problems in which fatty liver plays a role, it may be useful to opt for a form of lifestyle coaching, which is reimbursed by the health insurance company.

Content