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Non-alcoholic Fatty Liver Disease

What does the liver do?

The liver is in the upper right part of the abdomen. Its functions include:

  • Storing glycogen (fuel for the body) which is made from sugars. When required, glycogen is broken down into glucose which is released into the bloodstream.
  • Helping to process fats and proteins from digested food.
  • Making proteins that are essential for blood to clot (clotting factors).
  • Helping to remove or process alcohol, medicines, and toxins from the body.
  • Making bile which passes from the liver to the gut down the bile duct. Bile breaks down the fats in food so that they can be absorbed from the bowel.

What is non-alcoholic fatty liver disease?

Non-alcoholic fatty liver disease (NAFLD) describes a range of conditions caused by a build-up of fat within liver cells. It is helpful to divide NAFLD into four stages:

  • Simple fatty liver – also called hepatic steatosis. Normally, very little fat is stored in liver cells. Simple fatty liver means that excess fat accumulates in liver cells. For most people, simple fatty liver does not cause any harm or problems to the liver. However, in some people it can progress to more severe forms of NAFLD.
  • Non-alcoholic steatohepatitis – often called NASH. In this condition the excess fat in the liver cells is associated with, or may cause, inflammation of the liver. (Steato means fat, and hepatitis means inflammation of the liver). This is much less common than simple fatty liver.
  • Fibrosis: any form of persistent hepatitis, including steatohepatitis, may eventually cause scar tissue (fibrosis) to form within the liver. When fibrosis first develops often there are many liver cells that continue to function quite well.
  • Cirrhosis. Cirrhosis is a serious condition where normal liver tissue is replaced by a lot of fibrosis. The structure and function of the liver are badly disrupted. It is, in effect, like a severe form of liver fibrosis. Many liver conditions can lead to cirrhosis, including NAFLD. Severe cirrhosis can lead to liver failure. (See separate leaflet called ‘Cirrhosis’).

NAFLD occurs in people who do not drink excessive amounts of alcohol and so alcohol is not the cause. Most people with NAFLD have simple fatty liver. Only a minority progress to develop NASH. And, only a minority of people with NASH progress to cirrhosis. It is not clear why some people with simple fatty liver progress to the more severe forms of NAFLD, and most do not.

Other forms of fatty liver

A condition similar to NAFLD can affect people who do drink a lot of alcohol – see separate leaflet called ‘Alcohol and Liver Disease’. Another fatty liver condition called fatty liver of pregnancy is a rare, but serious condition of pregnancy. In this condition a lot of fat builds up in the liver cells and causes damage quite quickly. The cause is not known. Symptoms include vomiting, abdominal pain and jaundice.

The rest of this leaflet is only about NAFLD.

Who gets non-alcoholic fatty liver disease?

NAFLD is the most common chronic (persistent) liver disorder in western countries such as the UK. It is thought to occur in about 1 in 5 adults in the UK, and in up to 4 in 5 adults who are obese. (However, most of these people have ‘simple fatty liver’ and not the more serious types of NAFLD.)

The risk factors for developing NAFLD include:

  • Obesity. Most people with NAFLD are obese or overweight. However, the relationship between body fat and NAFLD, and factors that determine which people with obesity will develop NAFLD, are not clear. So, for example, some people who are only mildly overweight develop NAFLD. On the other hand, some people who are very obese do not develop NAFLD.
  • Diabetes. People with type 2 diabetes have an increased risk of developing NAFLD. However, there is no increased risk for those with type 1 diabetes.
  • Age. NAFLD is more common in people over 50 years. It is also more common in men.
  • Hypertension (high blood pressure). People with hypertension are at a greater risk of developing NAFLD.
  • Hyperlipidaemia (high level of blood fats). If you have high level of cholesterol and/or triglycerides in your blood then you have a higher risk of developing NAFLD.
  • Very rapid weight loss. For example, NAFLD develops in some people following surgery to reduce obesity. This may be due to rapid changes of fats and fatty acids in the blood that occur when weight loss is rapid.
  • Drugs. For example, methotrexate and tamoxifen can, rarely, cause NAFLD.

People with NAFLD have a higher chance of developing type 2 diabetes and cardiovascular disease (this includes heart attacks and strokes). Also, as NAFLD is common, some people with NAFLD also have another liver disorder, and NAFLD can make the other liver disorder worse.

What are the symptoms of non-alcoholic fatty liver disease?

Most people with simple fatty liver or NASH have no symptoms. However, some people with simple fatty liver or NASH have a nagging persistent pain in the upper right part of the abdomen, over an enlarged liver. You may feel generally tired if you have NASH. As most people do not have symptoms, the diagnosis is often first suspected when an abnormal blood test result occurs.

A small proportion of people with NAFLD develop cirrhosis. See leaflet called ‘Cirrhosis’ for a list of symptoms and problems that may develop with cirrhosis.

How is non-alcoholic fatty liver disease diagnosed?

There is no simple test that can confirm NAFLD. Blood tests called liver function tests (LFTs) measure the blood levels of certain enzymes (chemicals) made by the liver cells. An abnormal pattern of LFTs may suggest that you have NAFLD. However, many other liver conditions can cause abnormal LFTs. Therefore, if you have abnormal LFTs, a doctor will usually then do various other blood tests to rule out other causes of liver problems. For example, blood tests to detect various viruses and other liver-related chemicals.

LFTs are tests that are done for various reasons. Therefore, NAFLD is often first suspected when an abnormal result occurs when the tests are done for an unrelated reason.

A scan of the liver can be helpful. For example, an ultrasound scan, CT scan or MRI scan. The scan can show an enlarged liver compatible with the diagnosis of NAFLD. However, a scan cannot definitely diagnose NAFLD.

The diagnosis of NAFLD is usually based on the abnormal LFTs and scan being compatible with NAFLD, and ruling out other causes of liver problems. If there is doubt about the diagnosis, a specialist may arrange a biopsy (small sample) to be taken from your liver. This can be looked at under the microscope and can show the extent of any fatty accumulation, inflammation, scarring, etc, in the liver. See separate leaflet called ‘Biopsy – Liver’. However, a liver biopsy is not routinely done when simple fatty liver or NASH is the likely diagnosis as there is some risk involved when doing a liver biopsy. A liver biopsy is mainly done if the diagnosis is in doubt, or if there is concern that cirrhosis has developed.

What is the treatment for non-alcoholic fatty liver disease?

Treatment of obesity and overweight

Most cases of NAFLD are linked to being obese or overweight. There is good evidence that a programme of gradual weight loss and regular exercise can reduce the amount of fat in your liver. So, if you have simple fatty liver or mild NASH, this may prevent or delay the progression of NAFLD. It may reduce your chance of developing cirrhosis. In some people who are very obese, obesity surgery may be considered as studies have shown that this may help to improve NASH.

Treatment of linked conditions and risk factors

As mentioned, having NAFLD increases your risk of developing cardiovascular disease. In fact, people with NAFLD are actually more likely to become ill and die from cardiovascular diseases such as heart attack than from a liver problem. Therefore, your doctor is likely to stress the importance of reducing any ‘lifestyle’ risk factors that increase the risk of developing cardiovascular disease. For example, not smoking, keeping your weight in check, taking regular exercise, and eating a healthy balanced diet. See separate leaflet called ‘Preventing Cardiovascular Diseases’ for more details. Also, to treat high blood pressure and a high cholesterol level, if appropriate.

If you have diabetes, then good control of your blood glucose level is thought to help reduce the risk of NAFLD getting worse.

It is also advised that you do not drink any alcohol. NAFLD (by definition) is not caused by alcohol. However, even modest amounts of alcohol may make NAFLD worse.

Medication that affects the liver itself

Various drugs have been suggested as possible treatments for NAFLD. However, there is little research evidence to say that any drug works very well. For example, for NASH, no treatment has been proved to stop or reverse the inflammation. Various drugs are currently being trialled in different studies. One or more drugs may emerge as treatments in the future.

What is the outlook (prognosis)?

For most people with NAFLD, the condition does not progress beyond simple fatty liver or NASH. Cirrhosis and serious liver problems do not develop in most cases. The condition may reverse and even go away by weight loss (if you are overweight or obese) or with good control of diabetes (if diabetes is the cause).

However, fatty liver does progress to NASH in some people, and NASH progresses to cirrhosis in some people. It is not clear why some people with NASH, and not others, progress to cirrhosis. Cirrhosis is very serious, can lead to liver failure and be fatal.

It is estimated that, on average:

  • About 2 in 100 people with simple fatty liver progress to cirrhosis over 15-20 years.
  • About 12 in 100 people with NASH progress to cirrhosis over about 8 years.

So, most people with NAFLD do not develop serious liver disease. However, because NAFLD has become very common in recent years (probably because of the epidemic in obesity), NAFLD has become a common cause of cirrhosis.

But also remember, cardiovascular disease is the most common cause of illness and death in people with NAFLD. Perhaps the most important ‘take home message’ if you are diagnosed with NAFLD is not to focus too much on your liver. But, to concentrate on reducing any risk factors for developing cardiovascular problems. This is mainly lifestyle changes. In particular, diet, weight loss and exercise for most people, and giving up smoking if you smoke.

Further help and information

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References

  • Bhala N, Usherwood T, George J; Non-alcoholic fatty liver disease. BMJ. 2009 Jul 16;339:b2474. doi: 10.1136/bmj.b2474.
  • Vuppalanchi R, Chalasani N; Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: Selected practical issues in their evaluation and management. Hepatology. 2009 Jan;49(1):306-17. [abstract]
  • Jou J, Choi SS, Diehl AM; Mechanisms of disease progression in nonalcoholic fatty liver disease. Semin Liver Dis. 2008 Nov;28(4):370-9. Epub 2008 Oct 27. [abstract]
  • Kashi MR, Torres DM, Harrison SA; Current and emerging therapies in nonalcoholic fatty liver disease. Semin Liver Dis. 2008 Nov;28(4):396-406. Epub 2008 Oct 27. [abstract]
  • Argo CK, Iezzoni JC, Al-Osaimi AM, et al; Thiazolidinediones for the treatment in NASH: sustained benefit after drug discontinuation? J Clin Gastroenterol. 2009 Jul;43(6):565-8. [abstract]
  • Lam BP, Younossi ZM; Treatment regimens for non-alcoholic fatty liver disease. Ann Hepatol. 2009;8 Suppl 1:S51-9. [abstract]

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