This article was last reviewed and updated on December 17, 2018
by Stephanie Reid, MD FRCPC
Autoimmune hepatitis is a liver disease caused by cells from the immune system attacking and damaging the cells in the liver.
It happens to both women and men but it is three times more common in women.
The liver is an organ found in the right upper part of your abdominal cavity. It is responsible for removing toxins, processing medications, and producing substances such as bile that are essential for breaking down and using food.
The liver can be affected by diseases other than tumours. These are broadly referred to as ‘medical liver disease’. In these diseases, there is damage to specific cell types or areas of the liver.
The liver contains multiple types of cells which make up its structure and allow it to work normally. The most important type of cell in the liver is called a hepatocyte. The liver also has biliary cells which line the inside of long channels called bile ducts, and endothelial cells which line the inside of blood vessels. There are also a variety of background of cells and materials that support and hold all these other parts of the liver together. In medical liver disease, any of these cells or parts may be affected or damaged.
Some medical liver diseases belong to a special category called “autoimmune disease”. In this category of disease, your liver is damaged by cells from your immune system. These diseases are classified by which cells or liver structures are being damaged by the immune cells. The causes of autoimmune liver disease are not fully understood although some are associated with other medical conditions.
What is autoimmune hepatitis?
Autoimmune hepatitis is a type of autoimmune liver disease caused by immune cells damaging the hepatocytes in the liver. It occurs in all ages and is seen in women three to four times more often than in men. The clinical symptoms of autoimmune hepatitis vary. In some people there are no symptoms and the condition is discovered when routine blood work shows abnormalities in liver enzymes called AST and ALT. Another substance called IgG is often elevated.
Other patients with autoimmune hepatitis can first come to medical attention when they develop a condition called acute liver failure. This occurs when so much of the liver is damaged in such a short period of time that the liver stops working.
For most patients, however, the symptoms of autoimmune hepatitis are more mild and may include fatigue, loss of appetite, and abdominal pain. One third of patients develop cirrhosis which can cause the skin and eyes to turn yellow, a swollen abdomen, and bleeding of the stomach or esophagus.
If your doctor suspects that you may have autoimmune hepatitis, they will order blood work to look for specific markers that are present in the disease. In autoimmune hepatitis, these markers are called autoantibodies.
Types of autoimmune hepatitis
There are three types of autoimmune hepatitis and each is associated with different types of autoantibodies.
The three types of autoimmune hepatitis are:
Type 1 - This is the most common type of autoimmune hepatitis. Blood work will reveal anti-nuclear antibodies (ANA) and/or anti-smooth muscle antibodies (SMA). This type classically occurs in two age groups: young people (10-25) and at a later age (50-70).
Type 2 - This type of autoimmune hepatitis is most commonly seen in children, and rarely affects adults. Anti-liver/anti-kidney microsomal antibodies (anti-LKM-1) are found in the blood. This type of autoimmune hepatitis is often harder to control with medication, and usually has more episodes of disease activity (relapse) than the other types.
Type 3 - This type of autoimmune hepatitis is usually first diagnosed in adults aged 30-50. Anti-soluble liver antigen (anti-SLA) or liver pancreas antigen (LP) antibodies are found in the blood.
Patients with autoimmune hepatitis can experience several medical complications. In severe disease, a large amount of your liver may be affected, and this can result in sudden liver failure. Over time, the disease can also lead to liver cirrhosis, which increases the risk of liver failure and hepatocellular carcinoma (cancer of the liver cells).
If autoimmune hepatitis is suspected after blood work, your doctor may order a liver biopsy. After examining the tissue sample under the microscope, your pathologist will provide your doctor with a diagnosis. Your pathologist will also carefully examine the tissue sample to look for two important microscopic features that will help determine your prognosis: inflammation and fibrosis.
If these features are seen, the amount of inflammation will be given a grade and the amount of fibrosis will be given a stage. In people who already have a diagnosis of autoimmune hepatitis, biopsies may be ordered to see if the disease has responded to medications, and/or to monitor the amount of fibrosis in your liver.
There are five important microscopic features that your pathologist will look for when examining your tissue sample:
1. Lobular inflammation:
In autoimmune hepatitis cells from your immune system attack the hepatocytes in the liver. Different types of immune cells may be involved, however the two most common are called plasma cells and lymphocytes. Your pathologist may see single cells which are damaged (sometimes called “acidophil bodies” in your report) or there may be larger areas of damaged/dead hepatocytes.
2. Interface activity:
In autoimmune hepatitis, inflammation occurs in the area between the portal tract and the hepatocytes. This area is called the limiting plate or interface and inflammation in this area is called “interface activity”. Your pathologist will look for immune cells in this area causing damage to the hepatocytes.
3. Centrilobular activity:
In some patients with autoimmune hepatitis, inflammation occurs around a blood vessel called the central vein. Your pathologist will look for immune cells which are damaging the hepatocytes in this area.
4. Portal tract inflammation:
The portal tract is the area of the liver that contains the bile duct (which carries bile from the liver to the gallbladder) and two blood vessels. In autoimmune hepatitis, there may be an increased number of immune cells in the portal tract. Despite the increased number of immune cells, the bile duct and blood vessels are usually not damaged.
Fibrosis is a type of scar tissue that forms in the liver after damage. Because autoimmune hepatitis damages the liver, there is a risk of developing fibrosis. Most pathology reports comment on the amount of fibrosis and will give it a ‘stage’. The stage depends on a number of factors including the amount of injury, the length of time over which the injury was taking place, and the parts of the liver that were damaged. Too much fibrosis disrupts the architecture of the liver and prevents it from functioning properly.
There are several different classifications systems used to stage fibrosis but all of them include the type and amount of fibrosis seen. Cirrhosis is the last stage of fibrosis and it is characterized by large fibrous bands in the liver. Fibrosis prevents the liver from carrying out its normal functions and may lead to a medical condition called ‘liver failure’.
Other features that may be described in your report:
Steatosis is fat droplets inside the liver cells. The hepatocytes contain clear areas of fat droplets when viewed under a microscope. The amount of fat present is reported as follows:
Mild - fat droplets are seen within less than 33% of the hepatocytes in the biopsy
Moderate - fat droplets are seen within 33 - 66 % of hepatocytes in the biopsy
Severe - fat droplets are seen within greater than 66 % of hepatocytes in the biopsy.
Ballooning hepatocytes are liver cells which are damaged or dying. The hepatocyte swells to several times its normal size and becomes clear in areas. Ballooning hepatocytes are required for the diagnosis of several medical liver diseases. The amount of hepatocyte ballooning present is reported as mild, moderate, or severe.
The liver is divided into ‘zones’ and at the center of each zone is a structure called a ‘portal tract’. Portal tracts are important because they contain blood vessels and channels that move other substances such as bile in and out of the liver.
When examining a liver biopsy, your pathologist must first determine if the sample contains the minimum amount of portal tracts required to make an accurate diagnosis. The adequacy of the biopsy may be reported simply as “yes” or “no”, or the number of portal tracts seen may be stated.
The condition of the liver biopsy when viewed under the microscope is usually described. If the liver biopsy is brittle and has broken apart this will be described, as it may be a clue to specific liver conditions.
Mallory bodies form as a result of damage to hepatocytes. Microscopically they are dense pink material inside of the cells. Mallory bodies are present in specific forms of liver disease and their presence or absence helps guide pathologists to a diagnosis.
The liver produces a substance called bile which is used to remove toxins from the body and digest food. The bile produced in the liver drains through channels called bile ducts into the small bowel. Each portal tract contains one bile duct. Your pathologist will describe if bile duct damage has taken place or if there is active inflammation of the bile ducts seen.
Cholestasis is a word pathologists use to describe bile trapped in the liver. Trapped bile is important because it can cause liver injury. If cholestasis is seen, your pathologist will describe its location within the liver and the amount of trapped bile will be described as mild, moderate, or severe.
Iron can build up within the liver as a result of abnormal breakdown of iron, increased iron in the body (such as after multiple blood transfusions), or when the liver is not functioning properly (as in liver cirrhosis). This excess iron can be seen within the hepatocytes or within immune cells called macrophages. If iron is present in your tissue, your pathologist will report its location and severity.