Autoimmune hepatitis is a chronic inflammatory disease of the liver in which the body’s own immune system attacks the liver cells.
Autoimmune hepatitis (AIH) is a chronic inflammatory disease of the liver caused by a malfunctioning immune system. In this disease, immune cells produce proteins called autoantibodies that attack the body’s own liver cells, resulting in chronic inflammation of the liver (called hepatitis).
The cause of this immune system malfunction is not known. Genetic predisposition is thought to play a role, but this alone cannot explain the development of this chronic liver disease. In addition to hereditary (genetic) factors, viral or bacterial infections as well as the dysregulation of certain proteins (cytokines) that regulate the immune system and white blood cells (lymphocytes) has been proposed. It is assumed that several different factors must come together in order for autoimmune hepatitis to develop.
AIH can be relatively mild without major symptoms, and often goes unnoticed. However, it may also be accompanied by fibrosis of the liver (in which liver tissue is gradually replaced by connective tissue). This can result in cirrhosis (formation of scar tissue in the liver) which may eventually progress to acute liver failure. Approximately one-fourth of patients with autoimmune hepatitis already have cirrhosis at the time of their diagnosis.
Patients with AIH frequently have another cholestatic liver disease affecting the bile ducts such as primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC). AIH may also be associated with other autoimmune diseases that do not affect the liver, including an autoimmune thyroid disease (Hashimoto’s thyroiditis) or rheumatoid arthritis.
Autoimmune hepatitis is a rare disease that affects about 20 out of 100,000 people in Europe. The frequency of the disease appears to be increasing.
AIH can affect people of all ages, but disproportionately afflicts adolescents and people between the ages of 45 and 55 years old. Women develop the disease about three times more often than men.
Autoimmune hepatitis usually presents with non-specific symptoms. These symptoms include an enlarged liver, fatigue, exhaustion, itching, pain in the upper right abdomen, and joint pain (arthralgia). Other symptoms of AIH are reduced strength, loss of appetite, light or pale stools, dark urine, and sometimes fever.
Patients who have developed cirrhosis due to AIH frequently experience symptoms of chronic liver disease, including abnormal skin changes such as spider web-like red spots (spider angioma) or reddening palms of the hands (palmar erythema). At later stages, other symptoms of cirrhosis may occur such as jaundice (a yellow discoloration of the skin and mucosa), water accumulation in the abdomen (ascites), bleeding from varicose veins in the esophagus (esophageal varices) or the stomach, or neurological deficits resulting from a condition called hepatic encephalopathy.
Especially, abnormally high levels of liver enzymes (such as transaminases) in a blood test may be a sign of AIH. The suspicion of an autoimmune disease can be confirmed by detection of specific autoantibodies and increased levels of proteins called immunoglobulins. The levels of immunoglobulin G (IgG) in particular are usually increased in autoimmune hepatitis.
However, detection of autoantibodies alone does not confirm a diagnosis of AIH. It is therefore always necessary to rule out other potential causes for the symptoms and the abnormal blood test results. These other causes may include (viral) infections as well as toxic (medications, alcohol), metabolic (fatty liver disease, iron overload, excess copper accumulation) or other autoimmune liver diseases (primary biliary cholangitis, primary sclerosing cholangitis).
When the diagnosis of autoimmune hepatitis is suspected, the doctor will ask the patient about their precise symptoms. The doctor will try to gather the patient’s medical history by asking questions like when the patient first noticed the symptoms and how they have developed since then. Questions specifically about fatigue and joint issues will be asked.
The doctor will also ask the patient whether he or she has other autoimmune diseases. In addition, the medical history usually involves questions about any medications the patient is taking (including naturopathic medicines) and about alcohol consumption in order to rule out other possible causes of the liver disease.
This conversation will be followed by a physical examination, where the doctor will probe the abdomen by hand and check whether the liver is enlarged or sensitive to pressure. The doctor will also check for other signs of cirrhosis such as spider web-like red spots (spider angioma), yellow discoloration of the skin, and/or reddening of the palms of the hands (palmar erythema).
The most typical feature of AIH is the presence of autoantibodies - antibodies that target the body’s own structures. They can be detected in a blood test. Evidence of AIH includes detection of the following:
- Antibodies targeting nuclear antigens, abbreviated ANA,
- Antibodies targeting smooth muscle cells, called smooth muscle antibodies (SMA), and
- Antibodies targeting soluble liver antigens/liver-pancreas, abbreviated SLA/LP.
Imaging techniques are also used to confirm the diagnosis of AIH and to determine whether a patient already has fibrosis or cirrhosis of the liver. The first test performed is usually an ultrasound examination since it can be performed easily and is very convenient for patients.
A procedure called a Fibroscan is increasingly being used to analyze the stiffness of liver tissue. Fibroscan allows the detection of liver fibrosis, inflammation, and swelling.
To confirm a diagnosis of AIH, a liver biopsy is typically collected, and this tissue sample is examined under a microscope (histological examination). Histological verification of an inflammatory liver disease is a major requirement for the diagnosis of autoimmune hepatitis. This procedure is also used to determine the extent of the disease.
There is no cure for autoimmune hepatitis. Instead, treatment has two goals: reducing symptoms and preventing the chronic liver disease from progressing to liver fibrosis or cirrhosis.
Autoimmune hepatitis usually responds well to medications that suppress the immune system (immunosuppressants). Patients are typically treated with systemic or locally-acting corticosteroid medications (often called just steroids) during the acute phase of the disease. These drugs lower the overactive immune response, with the goal of bringing the disease under control (remission) as demonstrated by normal transaminase and IgG levels. This is followed by long-term treatment with an immunosuppressant in order to maintain remission (maintenance therapy). Using locally-acting steroids may help reduce the frequency of the typical side effects of steroids.
After medications have been taken for two years, the doctor may try to stop them. If this results in another flare-up of the disease, the medication must be resumed, usually lifelong.
If the disease progresses or decompensated cirrhosis occurs, a transplantation clinic should be contacted.
As with all chronic liver diseases, some liver-friendly lifestyle changes are necessary to prevent the disease from progressing. These include stopping alcohol and/or nicotine use whenever possible.
A balanced diet and a healthy lifestyle with regular exercise may improve well-being and prevent nutritional deficiencies in people with chronic liver diseases. Sufficient calcium and vitamin D intake should also be ensured in order to prevent bone degradation (osteoporosis).
Outlook and prognosis
Some people can have AIH without any symptoms. In these cases, the disease is usually diagnosed by accident, for example during a routine examination. However, in about 25 to 35% of patients, the disease presents as acute hepatitis (inflammation of the liver) and then progresses to a chronic liver disease.
Autoimmune hepatitis can greatly reduce life expectancy if left untreated. However, AIH patients typically respond well to treatment with medications. As long as patients do not yet have cirrhosis, the long-term prognosis is favorable with a normal life expectancy and good quality of life. Nevertheless, lifelong therapy with medication is usually necessary.