Autoimmune hepatitis

What is autoimmune hepatitis?

Hepatitis means inflammation of the liver. There are many causes of hepatitis. For example, alcohol excess and various viral infections are the common causes of hepatitis. Please read the separate leaflet called Hepatitis to read more about the liver, where it is and what it does, and about other causes of hepatitis.

Autoimmune hepatitis is an uncommon cause of chronic hepatitis. Chronic means that the inflammation is persistent or long-term. The chronic inflammation gradually damages the liver cells, which can result in serious problems.

What causes autoimmune hepatitis?

The cause is not clear. It is thought to be an autoimmune disease. Our immune system normally defends us against infection from bacteria, viruses and other germs. In people with autoimmune diseases the immune system attacks part or parts of the body as if they were foreign. This causes inflammation and may damage the affected part or parts of the body.

The immune system includes white blood cells and special proteins (antibodies) which attack and destroy foreign germs and materials. There are various different autoimmune diseases. For example, rheumatoid arthritis, myasthenia gravis, some forms of thyroid disease, and primary biliary cholangitis. The symptoms of each disease depend on which part or parts of the body are attacked by the immune system.

In some autoimmune diseases it is antibodies which do the damage. In autoimmune hepatitis, it is white blood cells called lymphocytes which are mainly involved. The lymphocytes attack the liver cells (hepatocytes) which causes inflammation and damage.

Triggers

It is not known why autoimmune hepatitis or other autoimmune diseases occur. Some factor may trigger the immune system to attack the body's own tissues. There are various theories as to possible triggers. For example, a virus, a medication or chemical or some other factor may trigger the disease.

There is also an inherited factor which makes some people more prone to autoimmune diseases. (That is, you may need to be genetically susceptible for a trigger to set off the disease.)

Types of autoimmune hepatitis

There are two types of autoimmune hepatitis: type 1 and type 2.

Type 1 autoimmune hepatitis

This is the most common type of autoimmune hepatitis. Women are more frequently affected than men and it can occur at any age. About half the people with type 1 autoimmune hepatitis also have another autoimmune disease.

Type 2 autoimmune hepatitis

Type 2 autoimmune hepatitis mostly affects children and young people. It is more common in girls than in boys.

There are also some variants of autoimmune hepatitis where the disease overlaps with other liver diseases called primary biliary sclerosis and primary sclerosing cholangitis.

How common is autoimmune hepatitis?

Autoimmune hepatitis is uncommon. It affects around 16-18 out of every 100,000 people in Europe. It is 3 or 4 times more likely to occur in women as it is in men. It can affect people at all ages.

Autoimmune hepatitis symptoms

Symptoms are extremely variable, and range from very mild to very severe. In many cases the symptoms develop gradually over weeks or months. At the beginning of the disease, many people have no symptoms at all. They may develop more symptoms as the disease progresses. The most common early symptoms include:

• Feeling more tired than usual.

• Feeling generally unwell.

• Joint and muscle pains which are usually worse in the mornings.

• Feeling sick (nauseated).

• Poor appetite.

• Itching.

• Tummy (abdominal) discomfort or bloating.

• Joint pain.

Jaundice can develop when the liver inflammation becomes worse. If you have jaundice, you turn a yellow colour, which is seen in your skin and eyes. You tend to notice it first when the whites of the eyes become yellow. This is due to a build-up of the chemical bilirubin which is made in the liver and spills into the blood in some liver conditions. (With jaundice due to hepatitis your urine goes dark, your stools (faeces) may go pale and and you tend to itch.)

Without treatment, in time the persistent inflammation causes liver damage and can lead to cirrhosis. Cirrhosis is like a scarring of the liver, which can cause serious problems and liver failure when it is severe. See the separate leaflet called Cirrhosis for more detail.

In some cases, the symptoms develop quickly over a few days with an acute hepatitis. (Acute means sudden in onset or of short duration.) This can cause a fairly sudden onset of:

• High temperature (fever).

• Tummy (abdominal) pain.

• Jaundice.

• Feeling sick.

• Being sick (vomiting).

• Feeling unwell.

In some of these cases, the acute hepatitis settles down to the more common type of chronic hepatitis. In some cases, the acute hepatitis becomes severe and rapidly leads to liver failure.

If left untreated, the time it takes from the onset of the condition until severe cirrhosis develops varies from person to person. However, with treatment, the inflammation can usually be controlled and the outlook (prognosis) is good.

How is autoimmune hepatitis diagnosed?

Many people with autoimmune hepatitis have no symptoms, or only vague symptoms, for quite some time in the early stages of the disease. Therefore, the diagnosis is often made when you have tests for an unrelated condition. When symptoms suggest that you have hepatitis, your doctor will normally arrange tests to confirm hepatitis and to find the cause of the hepatitis. Tests usually include:

• Blood tests called liver function tests. These measure the activity of chemicals (enzymes) and other substances made in the liver. This gives a general guide as to whether the liver is inflamed, and how well it is working. See the separate leaflet called Liver Function Tests for more detail. These tests can confirm that you have hepatitis, but not usually the cause of the hepatitis.

• An ultrasound scan of the liver may be done.

• Other blood tests can measure various auto-antibodies which occur in various autoimmune diseases. For example, antinuclear antibodies (ANAs) or smooth muscle antibodies (SMAs). Some of these auto-antibodies are raised in autoimmune hepatitis and indicate that this may be the cause of the hepatitis.

• A small sample (biopsy) of the liver is likely to be taken to look at under the microscope. Looking at a tiny piece of liver tissue this way can show inflammation and the extent of any scarring of the liver (cirrhosis). See the separate leaflet called Liver Biopsy for more detail. The type of cells involved in the inflammation usually help to confirm the diagnosis of autoimmune hepatitis, and to rule out other causes of hepatitis.

Various tests may also be done to rule out other liver disorders such as viral hepatitis.

Autoimmune hepatitis treatment

Treatment is almost always needed. Early treatment can improve symptoms, reduce the risk of complications, and also greatly improve your outlook (prognosis). Treatment aims to reduce inflammation and suppress the immune system with immunosuppressant medicines. Treatments include:

Steroids

Steroid medication (usually prednisolone) is often thel first treatment. Steroids are good at reducing inflammation. A high dose is usually needed at first. The dose is then gradually reduced over a few weeks. The aim is to find the lowest dose needed to control the inflammation. The dose needed varies from person to person. See the separate leaflet called Oral Steroids for more detail.

Immunosuppressants

Azathioprine is an immunosuppressant medicine that works in a different way to steroids. It is usually used in addition to the steroid. A steroid plus azathioprine tends to work better than either alone. Also, the dose of steroid needed is usually less if you also take azathioprine. This means that any side-effects from steroids may be less severe.

Treatment works well in most cases. Usually, the inflammation settles and symptoms improve within a few months of starting treatment. However, it may take a year or more to get the disease totally under control. Azathioprine is usually taken for at least two years.

Once the condition has completely settled, your doctor may advise a trial without treatment. A liver biopsy is usually done at the end of the course of treatment, to ensure that the liver inflammation has fully resolved. However, only around one in five people can remain off treatment for long periods of time. This is because the hepatitis usually returns (relapses), which means you will have to then take medication again.

In many cases, long-term maintenance treatment is needed. This means that the majority of people with autoimmune hepatitis will need to take low doses of immunosuppressant treatment for long periods of time, or even indefinitely.

Side-effects

Side-effects from the treatment may be troublesome in some cases. The dose of treatment is kept as low as possible to keep the condition under control with the minimum of side-effects. If you cannot tolerate the azathioprine and/or steroids then alternative treatment may be given. This may include other medicines such as mycophenolate mofetil, budesonide, ciclosporin or tacrolimus.

Side-effects from the steroids can occur. These can include 'thinning' of the bones (osteoporosis), weight gain, raised blood sugar and increased pressure in the eye (glaucoma). Your doctor may advise that you take vitamin D and calcium supplements, or medicines called bisphosphonates while you are taking steroid medication. These work by strengthening the bones and lowering your risk of developing osteoporosis in the future.

It is likely that you will be advised to have a dual-energy X-ray absorptiometry (DXA) scan before starting steroids and this is then repeated at regular intervals. This is done to assess the density of your bones. See the separate leaflet called Preventing Steroid-induced Osteoporosis.

Liver transplant

For some people a liver transplant may be an option - for example:

• In the few people who do not respond to treatment with the medicines mentioned above; or

• In people diagnosed in the late stage of the disease with severe 'scarring' of the liver (cirrhosis) or liver failure.

The long-term outlook after liver transplantation is good.

Vaccination

If you have autoimmune hepatitis it is recommended that you are vaccinated against hepatitis A and hepatitis B. You should also receive the annual flu vaccination.

Diet and alcohol

Most people with autoimmune hepatitis will be advised to eat a normal healthy diet. Ideally, anybody with inflammation of the liver should not drink alcohol, or only in very small amounts. If you already have liver inflammation, alcohol may increase the risk and speed of developing cirrhosis.

What is the outlook?

With treatment, most people with autoimmune hepatitis have a normal life expectancy and feel well most of the time. The treatment used for autoimmune hepatitis has improved the outlook (prognosis) tremendously.

It is very important that you do not stop your treatment too early without your doctor's knowledge, as your hepatitis may return. Although the condition usually returns at some point after stopping treatment, it can usually be treated again by quickly going back on medication.

There is a very small increased risk of developing liver cancer, especially if you also have 'scarring' of the liver (cirrhosis) due to your autoimmune hepatitis. Some doctors recommend a blood test and an ultrasound scan of your liver every so often to screen for this.