Autoimmune hepatitis

Definition

In autoimmune hepatitis, your body's immune system attacks your liver. Although the reason for this isn't entirely clear, some diseases, toxins and drugs may trigger autoimmune hepatitis in susceptible people, especially women.

Untreated autoimmune hepatitis can lead to scarring of the liver (cirrhosis) and eventually to liver failure. When diagnosed and treated early, however, autoimmune hepatitis often can be controlled with drugs that suppress the immune system. Yet these medications, which often must be taken long term, carry a number of risks and aren't always effective. A liver transplant may be an option when autoimmune hepatitis doesn't respond to drug treatments or in cases of advanced liver disease.

Symptoms

Signs and symptoms of autoimmune hepatitis can range from minor to severe and may come on suddenly or develop over time. Some people have few, if any, problems in the early stages of the disease, whereas others experience signs and symptoms that may include:

• Anemia
• Fatigue
• Abdominal discomfort
• Joint aches (arthralgias)
• Itching (pruritus)
• Yellowing of the skin and whites of the eyes (jaundice)
• An enlarged liver
• Abnormal blood vessels on the skin (spider angiomas)
• Nausea and vomiting
• Liver scarring (cirrhosis)
• Fluid in the abdomen (ascites)
• Mental confusion

It's common for people with autoimmune hepatitis to have other autoimmune disorders, such as:

• Hemolytic anemia, which occurs when red blood cells are destroyed faster than bone marrow can replace them
• Chronic inflammation of the thyroid gland (thyroiditis)
• Inflammation of the colon (ulcerative colitis)
• Diabetes
• Dry eyes and mouth (Sjogren's syndrome)
• Celiac sprue, a condition that damages the small intestine and leads to an inability to absorb certain nutrients

Causes

In autoimmune hepatitis, the body's immune system, which ordinarily attacks viruses, bacteria and other pathogens, instead targets the liver. Your body's attack on your liver can lead to chronic inflammation and serious damage to liver cells. Just why the body turns against itself is unclear, but autoimmune hepatitis appears to be triggered by:

• Infections. Autoimmune hepatitis can develop after such viral infections as acute hepatitis A, hepatitis B or measles or after infection with the Epstein-Barr virus. Epstein-Barr is one of the most common human viruses and linked to a number of disorders, including mononucleosis.
• Certain drugs. Some medications injure the liver directly — overdoses of the common pain reliever acetaminophen (Tylenol, others), for example, can cause liver failure. Other drugs harm the liver indirectly by stimulating an abnormal immune response that then harms liver cells.
• Genetic abnormalities. Some people seem genetically predisposed to develop autoimmune hepatitis. Researchers have identified certain gene abnormalities that increase the likelihood the disease will develop at a young age. Other genetic abnormalities may make autoimmune hepatitis more aggressive and harder to treat.

Types of autoimmune hepatitis
Doctors have identified two main forms of autoimmune hepatitis:

• Type 1 (classic) autoimmune hepatitis. Often developing suddenly, this is the most common type of the disease. Although it can occur in anyone at any age, most of those affected are young women. About half the people with type 1 autoimmune hepatitis have other autoimmune disorders, such as thyroiditis, rheumatoid arthritis or ulcerative colitis. Their blood also is likely to contain antibodies against organ tissue.
• Type 2 autoimmune hepatitis. Although adults can develop type 2 autoimmune hepatitis, it's most common in young girls and often occurs with other autoimmune problems.

Risk factors

Autoimmune hepatitis is uncommon. Having one or more risk factors for the disease doesn't mean that you'll develop it — only that you may be more susceptible than someone without these risk factors:

• Your sex. Although both men and women can develop autoimmune hepatitis, the disease is far more common in women.
• Age. Type 1 autoimmune hepatitis can occur in older adults, but it's most common in women between the ages of 15 and 40. Type 2 primarily affects young girls.
• A history of certain viral infections. Autoimmune hepatitis may develop after a viral infection, especially hepatitis A or B, measles, or infection with the Epstein-Barr virus.
• Use of certain medications. The high blood pressure drug methyldopa, the anti-inflammatory diclofenac, the antibiotics minocycline and nitrofurantoin, and perhaps atorvastatin (Lipitor) may trigger autoimmune hepatitis in some people.
• Heredity. Certain genetic defects increase the risk of autoimmune hepatitis.

When to seek medical advice

Schedule an appointment with your doctor
Early signs and symptoms of autoimmune hepatitis can be mild and may resemble those of the flu. See your doctor if you have:

• Persistent fatigue
• Abdominal discomfort
• Joint aches unrelated to exercise

See your doctor immediately
More serious symptoms require immediate care, especially if you have risk factors for autoimmune hepatitis. Such signs include:

• Yellowing of your skin and the whites of your eyes
• Abdominal swelling

Tests and diagnosis

Although your signs and symptoms can alert your doctor to the possibility of liver disease, you'll need certain tests to diagnose autoimmune hepatitis. These include:

• Blood tests. Antibody tests can distinguish autoimmune hepatitis from viral hepatitis and other disorders with similar symptoms. They also help pinpoint the type of autoimmune hepatitis you have.
• Liver biopsy. Doctors perform this test to confirm the diagnosis and to determine the degree and type of liver damage. During the procedure, a small amount of liver tissue is removed, using a thin needle that's passed into your liver through a small incision in your skin. The sample is then sent to a laboratory for analysis.

• Imaging tests. An abdominal ultrasound or abdominal computerized tomography (CT) scan can't diagnose autoimmune hepatitis, but doctors sometimes use these tests to help diagnose cirrhosis and to rule out liver cancer, a complication of cirrhosis.

  Magnetic resonance elastography (MRE) is a relatively new imaging test that may help your doctor diagnose cirrhosis and may help avoid the need for liver biopsy, which is more invasive. MRE technology works by combining traditional magnetic resonance imaging (MRI) with low-frequency sounds waves. The MRI component uses a magnetic field and radio waves to create clear and detailed cross-sectional images of your body, which show size and structure of your tissues and organs. The low-frequency sound waves then help reveal physical properties of those tissues and organs — such as tissue stiffness. Stiffness of your liver may indicate cirrhosis.

Complications

Autoimmune hepatitis may be associated with a variety of complications or other conditions, including:

• Pernicious anemia. Associated with a number of autoimmune disorders, pernicious anemia occurs when a lack of vitamin B-12 interferes with your body's ability to form red blood cells. Signs and symptoms of pernicious anemia can range from shortness of breath and a rapid heart rate to diarrhea, numbness or tingling in your hands and feet, and personality changes.
• Hemolytic anemia. In this type of anemia, your immune system attacks and breaks down red blood cells faster than your bone marrow can replace them.
• Thrombocytopenic purpura. Platelets are blood cells that play a crucial role in blood clotting. In thrombocytopenic purpura, your immune system attacks and destroys these cells, leading to easy bruising and bleeding.
• Ulcerative colitis. This inflammatory bowel disease can cause severe bouts of watery or bloody diarrhea and abdominal pain. It occurs in as many as two in 10 people with type 1 autoimmune hepatitis.
• Celiac disease. This disease causes an abnormal reaction to gluten, a protein found in most grains. Eating gluten sets off an immune response that damages the small intestine, affecting its ability to absorb nutrients.
• Autoimmune thyroiditis (Hashimoto's thyroiditis). In this condition, the immune system attacks the thyroid gland. In some people this causes the gland to secrete too little thyroid hormone (hypothyroidism). In others, the gland initially produces too much hormone (hyperthyroidism) and then produces too little.
• Type 1 diabetes. In type 1 diabetes, the immune system targets and destroys the insulin-producing cells in the pancreas. Insulin plays a vital role in making glucose — the body's fuel — available to cells. Without insulin, cells starve, and glucose builds up in the bloodstream. Diabetes is a serious illness that can damage organs throughout the body.
• Rheumatoid arthritis. Another autoimmune disease, rheumatoid arthritis occurs when the immune system attacks the lining of your joints, leading to stiffness, pain, swelling, and sometimes to deformity and disability.

Because symptoms don't always appear in the early stages of the disease, some people with autoimmune hepatitis develop irreversible scarring of liver tissue (cirrhosis) before they're ever diagnosed. Complications of cirrhosis include:

• Increased blood pressure in the vein that sends blood into the liver. Blood from your intestine, spleen and pancreas enters your liver through a large blood vessel called the portal vein. If scar tissue blocks normal circulation through your liver, this blood backs up, leading to increased pressure within the portal vein (portal hypertension).
• Enlarged veins (varices). When circulation through the portal vein is blocked, blood may back up into other blood vessels — mainly those in your stomach and esophagus. Sometimes veins also form around your navel and at the rectum. The blood vessels are thin walled, and because they're filled with more blood than they're meant to carry, they're likely to bleed. Massive bleeding in the upper stomach or esophagus from these blood vessels is a life-threatening emergency that requires immediate medical care.
• Fluid retention. Liver disease can cause large amounts of fluid to accumulate in your legs (edema) and abdomen (ascites). Several factors play a role, including portal hypertension and changes in the hormones and chemicals that regulate fluids in your body. Ascites can be uncomfortable and may interfere with breathing and is usually a sign of advanced cirrhosis.
• Bruising and bleeding. Scarring of the liver (cirrhosis) interferes with the production of proteins that help your blood clot and with the absorption of vitamin K, which plays a role in synthesizing these proteins. As a result you may bruise and bleed more easily than normal. Bleeding in the gastrointestinal tract is particularly common.
• Mental changes. A damaged liver has trouble removing toxins from your body — normally one of the liver's key tasks. The buildup of toxins such as ammonia — a byproduct of protein digestion — can damage your brain, leading to changes in your mental state, behavior and personality (hepatic encephalopathy). Symptoms of hepatic encephalopathy include forgetfulness, confusion and mood changes.
• Liver failure. This occurs when extensive damage to liver cells makes it impossible for your liver to function. At this point, a liver transplant is the only option.
• Liver cancer. Cirrhosis is one of the most common causes of hepatocellular carcinoma, the main form of liver cancer.

Treatments and drugs

The goal in treating autoimmune hepatitis is to inhibit your body's autoimmune response and slow the progress of the disease.

Prednisone
To achieve this, doctors usually prescribe an initial high dose of the corticosteroid drug prednisone, which suppresses the immune system. As soon as signs and symptoms improve, the medication is reduced to the lowest possible dose that controls the disease. Most people need to continue taking the drug for years, and sometimes for life. Although you may experience remission a few years after starting treatment, the disease usually returns when the drug is discontinued.

Prednisone side effects
Prednisone, especially when taken long term, can cause a wide range of serious side effects, including:

• Diabetes
• Thinning bones (osteoporosis)
• High blood pressure
• Glaucoma
• Difficulty fighting infection
• Thinning of your hair and skin
• Weight gain

Azathioprine (Imuran)
Because prednisone can cause such side effects, azathioprine, another immunosuppressant medication, is sometimes used along with prednisone. This helps lower the amount of prednisone needed, reducing its side effects.

Azathioprine (Imuran) side effects
Azathioprine has risks of its own, however, including:

• Decreased resistance to infection
• Nausea
• Rarely, liver damage and inflammation of the pancreas
• Rarely, cancer development after prolonged use

When these medications don't work
If you don't respond to these drugs or you have severe side effects, your doctor may prescribe cyclosporine or another immunosuppressant that may be effective. When medications don't halt the progress of the disease, or you have or develop irreversible scarring (cirrhosis) or liver failure, the remaining option is a liver transplant — a procedure that's often very successful in people with autoimmune hepatitis.