Autoimmune Hepatitis

On this page:

What is autoimmune hepatitis?
What is autoimmune disease?
What are the symptoms of autoimmune hepatitis?
How is autoimmune hepatitis diagnosed?
How is autoimmune hepatitis treated?
What are the side effects of prednisone and azathioprine?
Are other treatments for autoimmune hepatitis available?
Points to Remember
Hope through Research
For More Information

What is autoimmune hepatitis?

Autoimmune hepatitis affects the liver.

Autoimmune hepatitis is a disease in which the body’s immune system attacks liver cells. This immune response causes inflammation of the liver, also called hepatitis. Researchers think a genetic factor may make some people more susceptible to autoimmune diseases. About 70 percent of those with autoimmune hepatitis are female.

The disease is usually quite serious and, if not treated, gets worse over time. Autoimmune hepatitis is typically chronic, meaning it can last for years, and can lead to cirrhosis—scarring and hardening—of the liver. Eventually, liver failure can result.

Autoimmune hepatitis is classified as type 1 or type 2. Type 1 is the most common form in North America. It can occur at any age but most often starts in adolescence or young adulthood. About half of those with type 1 have other autoimmune disorders, such as

type 1 diabetes
proliferative glomerulonephritis, an inflammation of blood vessels in the kidneys
thyroiditis, an inflammation of the thyroid gland
Graves’ disease, the leading cause of overactive thyroid
Sjögren’s syndrome, a syndrome that causes dry eyes and mouth autoimmune anemia
ulcerative colitis, an inflammation of the colon and rectum leading to ulcers

Type 2 autoimmune hepatitis is less common, typically affecting girls aged 2 to 14, although adults can have it too.

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What is autoimmune disease?

One job of the immune system is to protect the body from viruses, bacteria, and other living organisms. The immune system usually does not react against the body’s own cells. However, sometimes it attacks the cells it is supposed to protect; this response is called autoimmunity. Researchers think certain bacteria, viruses, toxins, and drugs trigger an autoimmune response in people who are genetically susceptible to developing an autoimmune disorder.

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What are the symptoms of autoimmune hepatitis?

Fatigue is probably the most common symptom of autoimmune hepatitis. Other symptoms include

an enlarged liver
jaundice
itching
skin rashes
joint pain
abdominal discomfort
spider angiomas, or abnormal blood vessels, on the skin
nausea
vomiting
loss of appetite
dark urine
pale or gray-colored stools

People in advanced stages of the disease are more likely to have symptoms related to chronic liver disease, such as fluid in the abdomen—also called ascites—and mental confusion. Women may stop having menstrual periods.

Symptoms of autoimmune hepatitis range from mild to severe. Because severe viral hepatitis or hepatitis caused by a drug—for example, certain antibiotics—have the same symptoms as autoimmune hepatitis, tests may be needed for an exact diagnosis. Doctors should also review and rule out all medicines a patient is taking before diagnosing autoimmune hepatitis.

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How is autoimmune hepatitis diagnosed?

The doctor will make a diagnosis based on symptoms, blood tests, and a liver biopsy.

Blood tests. A routine blood test for liver enzymes can help reveal a pattern typical of hepatitis, but further tests, especially for autoantibodies, are needed to diagnose autoimmune hepatitis. Antibodies are proteins made by the immune system to fight off bacteria and viruses. Autoantibodies attack the body’s cells. In autoimmune hepatitis, the immune system makes one or more types of autoantibodies. The most common are antinuclear antibodies (ANA), smooth muscle antibodies (SMA), and antibodies to liver and kidney microsomes (anti-LKM). People with type 1 have ANA, SMA, or both, and people with type 2 have anti-LKM.
Blood tests also help distinguish autoimmune hepatitis from other diseases that resemble it, such as viral hepatitis B or C or a metabolic disease such as Wilson disease.
Liver biopsy. A tiny sample of liver tissue, examined with a microscope, can help doctors accurately diagnose autoimmune hepatitis and tell how serious it is. This procedure is done in a hospital or outpatient surgical facility.

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How is autoimmune hepatitis treated?

Treatment works best when autoimmune hepatitis is diagnosed early. With proper treatment, autoimmune hepatitis can usually be controlled. In fact, studies show that sustained response to treatment stops the disease from getting worse and may reverse some of the damage.

The primary treatment is medicine to suppress, or slow down, an overactive immune system.

Both types of autoimmune hepatitis are treated with daily doses of a corticosteroid called prednisone. Treatment may begin with a high dose of 30 to 60 mg per day and be lowered to 10 to 20 mg per day as the disease is controlled. The goal is to find the lowest possible dose that will control the disease.

Another medicine, azathioprine (Imuran) is also used to treat autoimmune hepatitis. Like prednisone, azathioprine suppresses the immune system, but in a different way. Treatment may begin with both azathioprine and prednisone, or azathioprine may be added later, once the disease is under control. The use of azathioprine allows for a lower dose of prednisone, which in turn reduces predisone’s side effects.

In about seven out of 10 people, the disease goes into remission within 3 years of starting treatment. Remission occurs when symptoms disappear and lab tests show improvement in liver function. Some people can eventually stop treatment, although many will see the disease return. People who stop treatment must carefully monitor their condition and promptly report any new symptoms to their doctor. Treatment with low doses of prednisone or azathioprine may be necessary on and off for years, if not for life.

Some people with mild forms of the disease may not need to take medication. Doctors assess each patient individually to determine whether those with mild autoimmune hepatitis should undergo treatment.

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What are the side effects of prednisone and azathioprine?

Both prednisone and azathioprine have side effects. Because high doses of prednisone are often needed to control autoimmune hepatitis, managing side effects is very important. However, most side effects appear only after a long period of time.

Some possible side effects of prednisone are

weight gain
anxiety and confusion
thinning of the bones, a condition called osteoporosis
thinning of the hair and skin
diabetes
high blood pressure
cataracts
glaucoma

Azathioprine can lower white blood cell counts and sometimes causes nausea and poor appetite. Rare side effects are allergic reaction, liver damage, and pancreatitis, which is an inflammation of the pancreas gland with severe stomach pain.

Autoimmune Hepatitis

By Howard J. Worman, M. D.

Autoimmune hepatitis is a condition in which the patient's own immune systems attacks the liver causing inflammation and liver cell death. The condition is chronic and progressive. Although the disease is chronic, many patients with autoimmune hepatitis present acutely ill with jaundice, fever and sometimes symptoms of severe hepatic dysfunction, a picture that resembles acute hepatitis.

Autoimmune hepatitis usually occurs in women (70 %) between the ages of 15 and 40. Although the term "lupoid" hepatitis was originally used to describe this disease, patients with systemic lupus erythematosus do not have an increased incidence of autoimmune hepatitis and the two diseases are distint entities. Patients usually present with evidence of moderate to severe hepatitis with elevated serum ALT and AST activities in the setting of normal to marginally elevated alkaline phosphatase and gamma-glutamyltranspeptidase activities. The patient will sometimes present with jaundice, fever and right upper quadrant pain and occasionally systemic symptoms such as arthralgias, myalgias, polyserositits and thrombocytopenia. Some patients will present with mild liver dysfunction and have only laboratory abnormalities as their initial presentation. Others will present with severe hepatic dysfunction.

Autoimmune hepatitis should be suspected in any young patient with hepatitis, especially those without risk factors for alcoholic, drug, metabolic or viral etiologies. Serum protein electrophoresis and testing for autoantibodies are of central importance in the diagnosis of autoimmune hepatitis. Patients with one subtype of autoimmune hepatitis have serum gamma-globulin concentrations more than twice normal and sometimes antinuclear antibodies and/or anti-smooth muscle (anti-actin) antibodies. Patients with another subtype may have normal or only slightly elevated serum gamma-globulin concentrations but will have antibodies against a particular cytochrome p450 isoenzyme that are called anti-LKM (liver kidney microsome).

Patients in whom a diagnosis of autoimmune hepatitis is suspected should have a liver biopsy. If the biopsy is consistent, treatment with steroids (prednisone or pednisolone) and azathioprine (Imuran) is begun immediately. These are tapered over the next 6 to 24 months depending upon the patient's course. If immediate liver biopsy is contraindicated because of a prolonged prothrombin time or thrombocytopenia, steroids and azathioprine should be started prior to biopsy if the diagnosis of autoimmune hepatitis is likely based on clinical criteria (e.g. a young woman with severe hepatitis, elevated serum gamma-globulin concentration, negative risk factors and serologies for viral hepatitis). The patient will often rapidly improve and biopsy should be performed to confirm the diagnosis as soon as the prothrombin time decreases and platelet count increases to within safe ranges.

About two thirds to three quarters of patients with autoimmune hepatitis respond to treatment based on the return of serum ALT and AST activities to normal and an improved biopsy after several months. Some patients relapse as steroids and azathioprine doses are tapered or stopped and need chronic maintenance medications. Over the long term, many patients develop cirrhosis despite having a response to treatment, and patients who do not respond to treatment will almost always progress to cirrhosis. If end-stage liver disease develops, orthotopic liver transplantation is an effective procedure.

For more information, you may want to see the following review articles:

Czaja, A.J. and Freese, D. K. 2002. Diagnosis and treatment of autoimmune hepatitis. Hepatology. 36:479-497.

Krawitt, E. L. 1996. Autoimmune hepatitis. New England Journal of Medicine. 334:897-903.