What is autoimmune hepatitis

Autoimmune hepatitis is a chronic—or long lasting—disease in which the body’s immune system attacks the normal components, or cells, of the liver and causes inflammation and liver damage 1). The immune system normally protects people from infection by identifying and destroying bacteria, viruses, and other potentially harmful foreign substances. The exact cause of autoimmune hepatitis is unclear, but genetic and environmental factors appear to interact over time in triggering the disease.

Untreated autoimmune hepatitis can lead to scarring of the liver (cirrhosis) and eventually to liver failure. Cirrhosis occurs when scar tissue replaces healthy liver tissue and blocks the normal flow of blood through the liver. Liver failure occurs when the liver stops working properly. When diagnosed and treated early, however, autoimmune hepatitis often can be controlled with drugs that suppress the immune system.

A liver transplant may be an option when autoimmune hepatitis doesn’t respond to drug treatments or when liver disease is advanced.

United States statistics

Epidemiologic data are limited. Among white adults, the prevalence is estimated to be 0.1-1.2 cases per 100,000 individuals. The frequency of autoimmune hepatitis among patients with chronic liver disease ranges from 11-23%. The disease accounts for about 6% of liver transplantations in the United States. Autoimmune hepatitis type 2 (AIH-2) and Autoimmune hepatitis type 3 (AIH-3) are observed infrequently in the United States, although AIH-2 is well characterized in Europe.

International statistics

The prevalence of autoimmune hepatitis is estimated to be 0.1-1.2 cases per 100,000 individuals in Western Europe. The reported prevalence of autoimmune hepatitis in Europe ranges from 11.6-16.9 cases per 100,000 persons. The reported prevalence is higher than the estimated prevalence. This is approximately the same prevalence as primary biliary cirrhosis and twice as high as the prevalence of primary sclerosing cholangitis. Autoimmune hepatitis accounts for about 3% of liver transplantations in Europe. The reported prevalence in Japan is only 0.08-0.015 cases per 100,000 persons in Japan.

The ratio of the incidence of autoimmune hepatitis type 1 (AIH-1) to autoimmune hepatitis type 2 (AIH-2) is 1.5-2:1 in Europe and Canada and 6-7:1 in North America, South America, and Japan. AIH-2 is more commonly described in southern Europe than in northern Europe, the United States, or Japan.

In an analysis of data from 33,379 patients with liver cirrhosis, Michitaka et al concluded that autoimmune hepatitis is the etiologic agent in 1.9% of such cases in Japan 2). Hepatitis C virus was the most prevalent etiologic agent, being associated with approximately 61% of cases of liver cirrhosis.)

What causes autoimmune hepatitis ?

A combination of autoimmunity, environmental triggers, and a genetic predisposition can lead to autoimmune hepatitis.

Autoimmune hepatitis occurs when the body’s immune system, which ordinarily attacks viruses, bacteria and other pathogens, instead targets the liver. This 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 researchers think autoimmune hepatitis could be caused by the interaction of genes controlling immune-system function and exposure to particular viruses or drugs.

Who is more likely to develop autoimmune hepatitis ?

Autoimmune hepatitis is more common in females 3). The disease can occur at any age and affects all ethnic groups.

Risk factors for autoimmune hepatitis

Factors that may increase your risk of autoimmune hepatitis include:

  • Being female. Although both men and women can develop autoimmune hepatitis, the disease is more common in women.
  • A history of certain infections. Autoimmune hepatitis may develop after you’re infected with the measles, herpes simplex or Epstein-Barr virus. The disease is also linked to hepatitis A, B or C infection.
  • Heredity. Evidence suggests that a predisposition to autoimmune hepatitis may run in families.
  • Having an autoimmune disease. People who already have an autoimmune disease, such as celiac disease, rheumatoid arthritis or hyperthyroidism (Graves’ disease or Hashimoto’s thyroiditis), may be more likely to develop autoimmune hepatitis.

What are the types of autoimmune hepatitis ?

Doctors have identified two main forms of autoimmune hepatitis:

Type 1 Autoimmune Hepatitis

Type 1 autoimmune hepatitis is the most common form in North America. Type 1 can occur at any age; however, it most often starts in adolescence or young adulthood. About 70 percent of people with type 1 autoimmune hepatitis are female 4).

People with type 1 autoimmune hepatitis commonly have other autoimmune disorders, such as:

  • Celiac disease, an autoimmune disease in which people cannot tolerate gluten because it damages the lining of their small intestine and prevents absorption of nutrients
  • Crohn’s disease, which causes inflammation and irritation of any part of the digestive tract
  • Graves’ disease, the most common cause of hyperthyroidism in the United States
  • Hashimoto’s disease, also called chronic lymphocytic thyroiditis or autoimmune thyroiditis, a form of chronic inflammation of the thyroid gland
  • Proliferative glomerulonephritis, or inflammation of the glomeruli, which are tiny clusters of looping blood vessels in the kidneys
  • Primary sclerosing cholangitis, which causes irritation, scarring, and narrowing of the bile ducts inside and outside the liver
  • Rheumatoid arthritis, which causes pain, swelling, stiffness, and loss of function in the joints
  • Sjögren’s syndrome, which causes dryness in the mouth and eyes
  • Systemic lupus erythematosus, which causes kidney inflammation called lupus nephritis
  • Type 1 diabetes, a condition characterized by high blood glucose, also called blood sugar, levels caused by a total lack of insulin
  • Ulcerative colitis, a chronic disease that causes inflammation and sores, called ulcers, in the inner lining of the large intestine.

Type 2 Autoimmune Hepatitis

Type 2 autoimmune hepatitis is less common and occurs more often in children than adults 5). People with type 2 can also have any of the above autoimmune disorders.

What is a possible complication of autoimmune hepatitis and cirrhosis ?

Autoimmune hepatitis that goes untreated can cause permanent scarring of the liver tissue (cirrhosis). Complications of cirrhosis include:

  • Enlarged veins in your esophagus (esophageal varices). When circulation through the portal vein is blocked, blood may back up into other blood vessels — mainly those in your stomach and esophagus. 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 esophagus or stomach from these blood vessels is a life-threatening emergency that requires immediate medical care.
  • Fluid in your abdomen (ascites). Liver disease can cause large amounts of fluid to accumulate in your abdomen. Ascites can be uncomfortable and may interfere with breathing and is usually a sign of advanced cirrhosis.
  • Liver failure. This occurs when extensive damage to liver cells makes it impossible for your liver to function adequately. At this point, a liver transplant is needed.
  • Liver cancer. People with cirrhosis have an increased risk of liver cancer.

People with autoimmune hepatitis and cirrhosis are at risk of developing liver cancer. A health care provider will monitor the person with a regular ultrasound examination of the liver. Ultrasound uses a device, called a transducer, that bounces safe, painless sound waves off organs to create an image of their structure. A specially trained technician performs the procedure in a health care provider’s office, an outpatient center, or a hospital, and a radiologist—a doctor who specializes in medical imaging—interprets the images; anesthesia is not needed. The images can show the liver’s size and the presence of cancerous tumors.

Eating, Diet, and Nutrition

Researchers have not found that eating, diet, and nutrition play a role in causing or preventing autoimmune hepatitis.

Autoimmune Hepatitis Prognosis

The prognosis of autoimmune hepatitis depends primarily on the severity of liver inflammation. Patients with a severe initial presentation tend to have a worse long-term outlook than patients whose initial disease is mild. Similarly, the inability to enter remission or the development of multiple relapses, either during therapy or after treatment withdrawal, implies a worse long-term prognosis.

Without treatment, nearly 50% of patients with severe autoimmune hepatitis will die in approximately 5 years, and most patients will die within 10 years of disease onset 6). Treatment with corticosteroids has been shown to improve the chances of survival significantly. The 10-year life expectancies for treated patients with and without cirrhosis at presentation are 89% and 90%, respectively. Indeed, the life expectancy of patients in clinical remission is similar to that of the general population.

Ferreira et al 7) concluded that immunosuppressive treatment improved the fibrosis scores, with an arrest in disease progression and no development of cirrhosis.  Despite an apparent initial response to immunosuppressive therapy, however, histologic progression may be gradual and require several years.

Greene and Whitington found that treatment fails in about 10% of patients, prompting alternative therapy and/or liver transplantation as the liver disease progresses. Less than 10% of patients with autoimmune hepatitis die during 10 years of follow-up 8).

In children with autoimmune hepatitis, 70% require treatment until adulthood. Many patients already have cirrhosis at the time of diagnosis. Almost 20-25% of children with autoimmune hepatitis die or require liver transplantation as a result of the disease. Guidelines published in 2011 by the British Society of Gastroenterology state that young patients with autoimmune hepatitis should receive immunosuppressive treatment to prevent or delay cirrhosis, even if they do not meet other treatment criteria 9).

HLA status affects treatment outcome. As an example, HLA DR3-positive patients are more likely to have active disease and are less responsive to therapy than patients with other HLA types. These patients also are more likely to require liver transplantation at some point.

Spontaneous resolution of the disease is observed in 13-20% of patients, regardless of the inflammatory activity. This is an unpredictable event.

In a series reported by Gregorio et al 10) in 1997, 70% of children with type 1 autoimmune hepatitis (AIH-1) and 40% of children with type 2 autoimmune hepatitis (AIH-2) developed cirrhosis. Of the 52 children, 17% had multiacinar or panacinar collapse with acute liver failure. The patients with the worst prognosis in this study, resulting either in death or liver transplantation, were those who were young at presentation and who had AIH-2, coagulopathy, high bilirubin counts, and severe initial histologic activity.

Hepatocellular carcinoma is less common in patients with autoimmune hepatitis–induced cirrhosis than in those with cirrhosis caused by other factors. Nevertheless, hepatocellular carcinoma is not a rare event in autoimmune hepatitis.

In general, the following factors are associated with a worse prognosis:

  • Young age at presentation
  • Type 2 autoimmune hepatitis (AIH-2)
  • Coagulopathy
  • Severe initial histologic activity

What are the symptoms of autoimmune hepatitis ?

Clinical features of autoimmune hepatitis widely vary. Most cases have an insidious onset. Patients may be asymptomatic or have nonspecific symptoms (eg, fatigue, anorexia, weight loss, behavioral changes, amenorrhea). Systemic or cutaneous abnormalities occur in 25% of patients. Epistaxis, bleeding gums, and bruises with minimal trauma are frequent complaints.

Autoimmune hepatitis may present as acute hepatitis, chronic hepatitis, or well-established cirrhosis. Autoimmune hepatitis rarely presents as fulminant hepatic failure.

Approximately one third of patients present with symptoms of acute hepatitis marked by fever, hepatic tenderness, and jaundice. In some patients, the acute illness may appear to resolve spontaneously; however, patients invariably develop signs and symptoms of chronic liver disease. Other patients experience rapid progression of the disease to acute liver failure, as marked by coagulopathy and jaundice. Ascites (fluid accumulation in your abdomen) and hepatic encephalopathy (a spectrum of neuropsychiatric abnormalities in patients with liver dysfunction – confusion, drowsiness and slurred speech) also may ensue.

The chronic hepatitis associated with autoimmune hepatitis may range in severity from a subclinical illness without symptoms and with abnormal results on liver chemistries to a disabling chronic liver disease. Symptoms and physical examination findings may stem from the various extrahepatic diseases associated with autoimmune hepatitis.

The most common symptoms of autoimmune hepatitis are:

  • fatigue
  • joint pain
  • In women, loss of menstruation
  • nausea
  • loss of appetite
  • pain or discomfort over the liver
  • skin rashes
  • dark yellow urine
  • light-colored stools
  • jaundice, or yellowing of the skin and whites of the eyes

Symptoms of autoimmune hepatitis range from mild to severe. Some people may feel as if they have a mild case of the flu. Others may have no symptoms when a health care provider diagnoses the disease; however, they can develop symptoms later.

How is autoimmune hepatitis diagnosed ?

A health care provider will make a diagnosis of autoimmune hepatitis based on symptoms, a physical exam, blood tests, and a liver biopsy.

A health care provider performs a physical exam and reviews the person’s health history, including the use of alcohol and medications that can harm the liver. A person usually needs blood tests for an exact diagnosis because a person with autoimmune hepatitis can have the same symptoms as those of other liver diseases or metabolic disorders.

Blood tests. A blood test involves drawing blood at a health care provider’s office or a commercial facility and sending the sample to a lab for analysis. A person will need blood tests for autoantibodies to help distinguish autoimmune hepatitis from other liver diseases that have similar symptoms, such as viral hepatitis, primary biliary cirrhosis, steatohepatitis, or Wilson disease.

Liver biopsy. A liver biopsy is a procedure that involves taking a piece of liver tissue for examination with a microscope for signs of damage or disease. The health care provider may ask the patient to temporarily stop taking certain medications before the liver biopsy. He or she may also ask the patient to fast for 8 hours before the procedure.

During the procedure, the patient lies on a table, right hand resting above the head. A health care provider will apply a local anesthetic to the area where he or she will insert the biopsy needle. If needed, he or she will give sedatives and pain medication. Then, he or she will use a needle to take a small piece of liver tissue, and may use ultrasound, computerized tomography scans, or other imaging techniques to guide the needle. After the biopsy, the patient must lie on the right side for up to 2 hours and is monitored an additional 2 to 4 hours before being sent home.

A health care provider performs a liver biopsy at a hospital or an outpatient center. The liver sample is sent to a pathology lab where the pathologist—a doctor who specializes in diagnosing disease—looks at the tissue with a microscope and sends a report to the patient’s health care provider.

A health care provider can use liver biopsy to diagnose autoimmune hepatitis and determine if cirrhosis is present. People often have cirrhosis at the time they are diagnosed with autoimmune hepatitis. A health care provider can also use liver biopsy to look for changes in the severity of liver damage prior to ending treatment for autoimmune hepatitis.

How is autoimmune hepatitis treated ?

Whatever type of autoimmune hepatitis you have, the goal of treatment is to suppress, slow down or stop the immune system attack on your liver. This may help slow the progression of the disease. To meet this goal, you’ll need medications that lower immune-system activity. Treatment with prednisone is generally used initially. A second medication, azathioprine (Azasan, Imuran), may be recommended in addition to prednisone.

Treatment may also include a liver transplant.

Treatment works best when autoimmune hepatitis is diagnosed early. People with autoimmune hepatitis generally respond to standard treatment and the disease can be controlled in most cases. Long-term response to treatment can stop the disease from getting worse and may even reverse some damage to the liver.

Medications

People with autoimmune hepatitis who have no symptoms or a mild form of the disease may or may not need to take medication. A health care provider will determine if a person needs treatment. In some people with mild autoimmune hepatitis, the disease may go into remission. Remission is a period when a person is symptom-free and blood tests and liver biopsy show improvement in liver function.

Corticosteroids. Corticosteroids are medications that decrease swelling and reduce the activity of the immune system. Health care providers treat both types of autoimmune hepatitis with a daily dose of a corticosteroid called prednisone. Treatment may begin with a high dose that is gradually lowered as the disease is controlled. The treatment goal is to find the lowest possible dose that helps control the disease.

For more than 3 decades, corticosteroids, either alone or in combination with azathioprine, have been the mainstays of drug therapy for patients with autoimmune hepatitis 11). The American Association for the Study of Liver Diseases and the British Society of Gastroenterology recommend combination therapy, using the corticosteroid prednisone with azathioprine.

Side effects of prednisone may include:

A health care provider will closely monitor and manage any side effects that may occur, as high doses of prednisone are often prescribed to treat autoimmune hepatitis.

Immune system suppressors. Medications that suppress the immune system prevent the body from making autoantibodies and block the immune reaction that contributes to inflammation. In most cases, health care providers use azathioprine (Azasan, Imuran) in conjunction with prednisone to treat autoimmune hepatitis. When using azathioprine, a health care provider can use a lower dose of prednisone, which may reduce prednisone’s side effects.

Side effects of azathioprine include:

  • low white blood cell count
  • nausea
  • vomiting
  • skin rash
  • liver damage
  • pancreatitis, or inflammation of the pancreas

Azathioprine is an immune system suppressor, so people taking the medication should undergo routine blood tests to monitor their white blood cell counts. A low white blood cell count can lead to bone marrow failure. Bone marrow is the tissue found inside bones that produces new blood cells, including platelets. A health care provider will also check the platelet count when blood tests are done.

A person may need to discontinue prednisone or azathioprine if they cause severe side effects. The risk of side effects is higher in people who also have cirrhosis.

A health care provider may gradually reduce the dose of medication in people who show improvement, although the symptoms can return. When a person discontinues treatment, a health care provider will perform routine blood tests and carefully monitor the person’s condition for a return of symptoms. Treatment with low doses of prednisone or azathioprine may be necessary on and off for many years.

People who do not respond to standard immune therapy or who have severe side effects from the medications may benefit from other immunosuppressive agents such as mycophenolate mofetil (CellCept), cyclosporine, or tacrolimus (Hecoria, Prograf).

Medications that suppress the immune system may lead to various forms of cancer. People on low doses of azathioprine for long periods of time are at slight risk of developing cancer.

Liver Transplant

In some people, autoimmune hepatitis progresses to cirrhosis and end-stage liver failure, and a liver transplant may be necessary. Symptoms of cirrhosis and liver failure include the symptoms of autoimmune hepatitis:

  • generalized itching
  • a longer-than-usual amount of time for bleeding to stop
  • easy bruising
  • a swollen stomach or swollen ankles
  • spiderlike blood vessels, called spider angiomas, that develop on the skin
  • abdominal bloating due to an enlarged liver
  • fluid in the abdomen—also called ascites
  • forgetfulness or confusion

Liver transplant is surgery to remove a diseased or an injured liver and replace it with a healthy one from another person, called a donor. A team of surgeons performs a liver transplant in a hospital. When possible, the patient fasts for 8 hours before the surgery. The patient stays in the hospital about 1 to 2 weeks to be sure the transplanted liver is functioning properly. The health care provider will monitor the patient for bleeding, infections, and signs of liver rejection. The patient will take prescription medications long term to prevent infections and rejection. Liver transplant surgery for autoimmune hepatitis is successful in most cases.

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