Autoimmune Hepatitis

Illustration of the digestive system including the liver. Source: National Digestive Diseases Information Clearinghouse (NDDIC)

Autoimmune hepatitis is a disease in which the body's immune system attacks the cells of the liver, causing inflammation and cell death. The disease is a serious one and, if not treated, gets worse over time. It can lead to cirrhosis (scarring and hardening of the liver) and eventually to liver failure.

Other Names

• Lupoid hepatitis

Types

There are three types of autoimmune hepatitis. They differ in the types of antibodies found in the blood. Antibodies are proteins made by the immune system to attack foreign invaders, but in this case the immune system has made them against the body itself.

The presence of antinuclear antibodies (ANA) or smooth muscle antibodies (SMA) leads to classification as Type I autoimmune hepatitis. Type II autoimmune hepatitis patients do not have ANA or SMA antibodies, but they do have liver-kidney microsomal antibodies (LKMI).

Type I

Type I, or classic autoimmune hepatitis, is the most common. It affects primarily young women. About half of those affected by autoimmune hepatitis have other autoimmune disorders too, such as type 1 diabetes, proliferative glomerulonephritis, thyroiditis, Graves disease, Sjögren syndrome, autoimmune anemia, and ulcerative colitis.

Type II

Type II autoimmune hepatitis is less common, typically affecting girls ages 2 to 14, although adults can also be affected. This type of autoimmune hepatitis is also associated with other autoimmune problems.

Type III

There is also a group of patients who do not have any of the above antibodies. They are classified as having Type III autoimmune hepatitis.

The severity of disease is thought to depend more on the age of onset than on the antibodies present. There is not much difference in disease outcome or response to treatment among the three types of autoimmune hepatitis. The terms are still commonly used (especially Type I and II) because some believe that the way the liver is damaged may be different.

Symptoms

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

• Enlarged liver
• Jaundice
• Itching (pruritus)
• Skin rashes
• Joint pain
• Abdominal discomfort
• Fatigue
• Spider angiomas (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 such as ascites (fluid in the abdomen) or mental confusion.

Causes

The immune system protects the body from viruses, bacteria, and other living organisms. Usually, the immune system does not react against the body's own cells; this is called self-tolerance. However, sometimes it mistakenly attacks the cells it is supposed to protect. This response is called autoimmunity. Researchers speculate that certain bacteria, viruses, toxins, and drugs trigger an autoimmune response in people who are genetically susceptible to developing an autoimmune disorder. The body may mistakenly attack parts of itself that bear proteins similar to those found in the germs, a situation called molecular mimicry. Two types of cells in the immune system—CD4+ cells and natural killer cells—are thought to be responsible for autoimmune hepatitis' attacks on the liver.^[1]

Diagnosis

Symptoms of autoimmune hepatitis range from mild to severe. Because viral hepatitis and hepatitis caused by medication have similar symptoms to autoimmune hepatitis, further testsing may be needed for an exact diagnosis. There is also a set of diagnostic criteria for autoimmune hepatitis. ^[2] These criteria are:

• No genetic liver disease
• No active viral infection
• Elevated serum transaminase levels (ALT and AST) in the blood (these are enzymes that indicate liver damage)
• Elevated ANA, SMA, or anti-KLM1 antibodies in the blood
• No evidence of other liver or gallbladder disease explaining the symptoms

Some methods used to arrive at a diagnosis are:

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. In autoimmune hepatitis, the immune system makes antinuclear antibodies (ANA), antibodies against smooth muscle cells (SMA), or liver and kidney microsomes (anti-LKM). The pattern and level of these antibodies help define the type of autoimmune hepatitis (type I or type II). Blood tests also help distinguish autoimmune hepatitis from viral hepatitis (such as hepatitis B or C) or a metabolic disease (such as Wilson disease).

Liver biopsy

A small sample of liver tissue, examined under a microscope, can help to accurately diagnose autoimmune hepatitis and determine the severity of the disease. This procedure is done at a hospital or outpatient surgical facility.

Treatment

Treatment works best when autoimmune hepatitis is diagnosed early. Approximately 60%–70% of patients respond well to treatment. With proper treatment, autoimmune hepatitis can usually be controlled. In fact, recent studies show that sustained response to treatment not only stops the disease from getting worse, but also may actually reverse some of the damage. ^[3]

The primary treatment is medication to suppress an overactive immune system.

Medication

• Autoimmune hepatitis is most commonly treated with daily doses of a corticosteroid called prednisone. It is often started at a relatively high dose (20 to 60 mg per day) and lowered the to 5 to 15 mg/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. It helps lower the dose of prednisone needed, thereby reducing its side effects. Azathioprine is often prescribed in addition to prednisone, once the disease is under control. Most people will need to take prednisone, with or without azathioprine, for years. Some take it for life.

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

Some possible side effects of prednisone are

• Weight gain
• Anxiety and confusion
• Thinning of the bones (osteoporosis)
• Thinning of the hair and skin
• Diabetes
• High blood pressure
• Cataracts
• Glaucoma

Azathioprine can lower the white blood cell count and may cause nausea and poor appetite. Rare side effects are allergic reaction, liver damage, and pancreatitis.

Liver transplant

People who progress to end stage liver disease (liver failure) and/or cirrhosis may need a liver transplant. Transplantation has a 1-year survival rate of 90 percent and a 5-year survival rate of 70 to 80 percent.

Chances of Developing Autoimmune Hepatitis

Autoimmune hepatitis is uncommon. In the United States it affects 100,000–200,000 people.^[4]

About 70% of those with autoimmune hepatitis are women, most between the ages of 15 and 40.

Clinical Trials

For a list of American government-sponsored trials involving research into autoimmune hepatitis, visit ClinicalTrials.gov.

Research

Scientists are studying various aspects of autoimmune hepatitis to find out who gets it and why and to discover better ways to treat it. Basic research on the immune system will expand knowledge of autoimmune diseases in general. Epidemiologic research will help doctors understand what triggers autoimmune hepatitis in some people. Research on different steroids, alternatives to steroids, and other immunosuppressants will eventually lead to more effective treatments.

• Cyclosporine shows promise in the treatment of autoimmune hepatitis in children. ^[5]
• Researchers at the University of South Carolina are studying the plant derivative cannabidiol as a possible treatment for autoimmune hepatitis. ^[6]
• Budesonide shows promise in treating (inducing remission) in autoimmune hepatitis ^[7]

Expected Outcome

In about one out of every three people, treatment can eventually be stopped. Some patients may relapse as medication is withdrawn. The relapsed hepatitis may be more severe. ^[8] In 7 out of 10 people, the disease goes into remission, with a lessening of severity of symptoms, within 2 years of starting treatment. The disease may return within 3 years after remission, so treatment may be necessary on and off for years, if not for life.

Epidemiology

Incidence

Among white northern Europeans, the incidence of autoimmune hepatitis (the number of new cases per year) is about 1.9 per 100,000 people per year.^[4]

Prevalence

Among white northern Europeans, the prevalence of autoimmune hepatitis (the number of people who have the disease on an ongoing basis) is about 16.9 per 100,000 people per year.^[4]

References

1. ↑ Czaja AJ. Current concepts in autoimmune hepatitis. Ann Hepatol. 2005 Jan-Mar;4(1):6-24. Abstract
2. ↑ Czaja A, Freese D;; American Association for the Study of Liver Disease. Diagnosis and treatment of autoimmune hepatitis. Hepatology. 2002; 36(2): 479-97. Abstract | PDF
3. ↑ Heneghan M, McFarlane I. Current and novel immunosuppressive therapy for autoimmune hepatitis. Hepatology. 2002 Jan;35(1):7-13. Abstract
4. ↑ ^{4.0 4.1 4.2} Czaja AJ. Autoimmune hepatitis--approach to diagnosis. MedGenMed. 2006 May 23;8(2):55. Abstract | Full Text
5. ↑ Alvarez F, Ciocca M, Cañero-Velasco C et al. Short-term cyclosporine induces a remission of autoimmune hepatitis in children. J. Hepatol. 1999 Feb;30(2):222-7. Abstract
6. ↑ University of South Carolina School of Medicine Web site. Cannabidiol-induced apoptosis in T cells to treat autoimmune hepatitis. Summary
7. ↑ Csepregi A, Röcken C, Treiber G, Malfertheiner P. Budesonide induces complete remission in autoimmune hepatitis. World J Gastroenterol. 2006 Mar 7;12(9):1362-6. Abstract
8. ↑ Al-Chalabi T, Heneghan M. Remission in autoimmune hepatitis: what is it, and can it ever be achieved? Am J Gastroenterol. 2007 May;102(5):1013-5. Abstract

External Links

American Liver Foundation (ALF)

Autoimmune Hepatitis Support Group (UK)