Auto Immune MAYO CLINIC BIOPSY REQ

January 8, 2007

Original

Article:http://www.mayoclinic.com/health/autoimmune-hepatitis/DS00676

Autoimmune hepatitis

Introduction

A number of factors can cause the serious liver disease hepatitis,

including viral infections, alcohol and certain drugs. But in autoimmune

hepatitis, the problem is different: Your body's own 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.

Signs and 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) or mental confusion, in advanced cases

It's common for people with autoimmune hepatitis to have other autoimmune

disorders, such as:

Hemolytic anemia, a type of anemia that occurs when red blood cells are

destroyed faster than the 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)

Causes

CLICK TO ENLARGE

The liver

The liver is not only the largest internal organ in your body, it's also

one of the hardest working and most complex. It performs hundreds of vital

functions, including processing most nutrients, producing bile and

blood-clotting factors, and removing drugs, alcohol and other harmful

substances from your bloodstream. Because the constant exposure to a

multitude of toxins can damage the liver and lead to hepatitis, many cases

of hepatitis are alcohol or drug related.

But in autoimmune hepatitis, the threat is much closer to home. The body's

immune system, which ordinarily attacks viruses, bacteria and other

pathogens, instead targets the liver, leading to chronic inflammation and

increasingly 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 a viral infection such

as acute hepatitis A, hepatitis B, measles or Epstein-Barr virus

infection. 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. These drugs

include interferon, which is commonly used to treat cancer, the high blood

pressure medication methyldopa/hydrochlorothiazide (Aldoril), antibiotics

such as minocycline — often used to treat adolescent acne — and

nitrofurantoin, the anti-inflammatory diclofenac, and possibly the

cholesterol drug atorvastatin (Lipitor).

Genetic abnormalities. Some people seem genetically predisposed to develop

autoimmune hepatitis. Researchers have identified certain gene deletions

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 is

also 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. Researchers once thought that type 2 autoimmune

hepatitis was more difficult to treat than type 1 is, but it now appears

that both respond equally well to steroid therapy.

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 than it is in men.

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/hydrochlorothiazide (Aldoril), 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

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 or joint aches unrelated to exercise. More serious

symptoms, such as yellowing of your skin and the whites of your eyes or

abdominal swelling, require immediate care, especially if you have risk

factors for autoimmune hepatitis.

Screening and diagnosis

Although your 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. Antibodies are immune

system proteins that normally attack harmful viruses and bacteria. But in

autoimmune hepatitis, the antibodies attack the liver.

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 imaging tests to rule out liver cancer, a complication of

cirrhosis.

Complications

Autoimmune hepatitis can cause a variety of complications, including:

Pernicious anemia. Associated with a number of autoimmune disorders,

pernicious anemia occurs when a lack of vitamin B12 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

three 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 surface of the small intestine, affecting the intestine's

ability to absorb nutrients from food.

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 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 from 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.

Treatment

The goal in treating autoimmune hepatitis is to inhibit your body's

autoimmune response and slow the progress of the disease. 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, 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

For that reason, azathioprine (Imuran), another immunosuppressant

medication, is sometimes used along with prednisone. This helps lower the

amount of prednisone needed, reducing its side effects. Azathioprine has

risks of its own, however, including decreased resistance to infection,

nausea, and in rare cases, liver damage and inflammation of the pancreas

(pancreatitis).

If you don't respond to these drugs or you have severe side effects, your

doctor may prescribe cyclosporine or another immunosuppressant medication

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.

By Mayo Clinic Staff

Feb 28, 2006

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DS00676

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January 8, 2007