Autoimmune hepatitis is a chronic inflammatory autoimmune disease of the liver. It usually occurs by itself, but it can coexist with other autoimmune diseases. Autoimmune hepatitis is liver inflammation that occurs when your body’s immune system turns against liver cells. The exact cause of autoimmune hepatitis is unclear, but genetic and environmental factors appear to interact over time in triggering the disease. The male/female ratio is 8:1, and it most often occurs in persons of Northern European extraction. It is usually classified as Type I or Type II. Type I is the most common and occurs at any age, most commonly in women. Type II is less common, affecting mostly girls between the ages of two to fourteen, although adults can have it too.
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. The disease can be quite serious and, if not treated, gets worse over time, leading to cirrhosis of the liver and/or liver failure. Autoimmune hepatitis likely results from a combination of autoimmunity, environmental triggers, and a genetic predisposition. It occurs more frequently in females. Treatment typically includes corticosteroids and medications that suppress the immune system. In severe cases, a liver transplant may be needed.[1][2]
Causes
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.
Types of autoimmune hepatitis
Doctors have identified two main forms of autoimmune hepatitis.
- Type 1 autoimmune hepatitis. This is the most common type of the disease. It can occur at any age. About half the people with type 1 autoimmune hepatitis have other autoimmune disorders, such as celiac disease, rheumatoid arthritis or ulcerative colitis.
- Type 2 autoimmune hepatitis. Although adults can develop type 2 autoimmune hepatitis, it’s most common in children and young people. Other autoimmune diseases may accompany this type of autoimmune hepatitis.
At this time, the exact cause of autoimmune hepatitis is unknown. It is believed to be due to a combination of environmental, genetic, and immunologic factors. A few environmental triggers, such as prescribed medications and infections, have been associated with the development of AIH. Some of the medications thought to play a role in those with drug-induced AIH include nitrofurantoin, minocycline, and hydralazine. Infections such as viral hepatitis (hepatitis A, B, C, and D), herpes simplex virus, and cytomegalovirus have also been linked to disease onset.
AIH is considered an “autoimmune” disease which means something (whether environmental, genetic, and/or immunologic factors) somehow triggers the immune system to think the cells in your liver are dangerous. This causes the cells in your body that usually attack foreign invaders (like viruses and bacteria) to start attacking the liver. This leads to inflammation and liver damage.
Symptoms
Signs and symptoms of autoimmune hepatitis vary from person to person and may come on suddenly. Some people have few, if any, recognized problems in the early stages of the disease, whereas others experience signs and symptoms that may include:
- Fatigue
- Abdominal discomfort
- Yellowing of the skin and whites of the eyes (jaundice)
- An enlarged liver
- Abnormal blood vessels on the skin (spider angiomas)
- Skin rashes
- Joint pains
- Loss of menstrual periods
- Fatigue (the most common symptom reported).
- Nausea.
- Loss of appetite.
- Diarrhea.
- Jaundice (yellowing of the skin and whites of the eyes).
Other signs and symptoms that may develop as the disease progresses include:[1][2][3][4]
- Loss of brain function (hepatic encephalopathy).
- Fluid in the abdomen (ascites).
- Swelling of the legs (edema).
- Easy bruising and bleeding.
- An enlarged spleen (splenomegaly).
- Gallstones.
- Itchy skin (pruritis) or skin rashes.
- Joint pain.
- Vomiting.
- Dark urine.
- Pale or gray-colored stools.
- Absence of menstrual periods in women (amenorrhea).
Some symptoms a person experiences may be due to other underlying heath conditions or autoimmune diseases that are associated with autoimmune hepatitis.[1][2][3]
This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.
| Medical Terms | Other Names |
Learn More:
HPO ID
|
|---|---|---|
| 100% of people have these symptoms | ||
| Increased circulating IgG level | 0003237 | |
| 80%-99% of people have these symptoms | ||
| Anti-liver cytosolic antigen type 1 antibody positivity | 0030909 | |
| Antineutrophil antibody positivity | 0003453 | |
| Antinuclear antibody positivity | 0003493 | |
| Elevated hepatic transaminase |
High liver enzymes
|
0002910 |
| Liver kidney microsome type 1 antibody positivity | 0030908 | |
| Smooth muscle antibody positivity | 0003262 | |
| 30%-79% of people have these symptoms | ||
| Abdominal pain |
Pain in stomach
[ more ] |
0002027 |
| Arthralgia |
Joint pain
|
0002829 |
| Chronic fatigue |
Chronic extreme exhaustion
|
0012432 |
| Depressivity |
Depression
|
0000716 |
| Spider hemangioma | 0012522 | |
| 5%-29% of people have these symptoms | ||
| Acute hepatitis |
Acute liver inflammation
|
0200119 |
| Anxiety |
Excessive, persistent worry and fear
|
0000739 |
| Arthritis |
Joint inflammation
|
0001369 |
| Ascites |
Accumulation of fluid in the abdomen
|
0001541 |
| Cirrhosis |
Scar tissue replaces healthy tissue in the liver
|
0001394 |
| Diffuse hepatic steatosis | 0006555 | |
| Gastrointestinal hemorrhage |
Gastrointestinal bleeding
|
0002239 |
| Glomerulonephritis | 0000099 | |
| Increased total bilirubin |
High bili total
|
0003573 |
| Jaundice |
Yellow skin
[ more ] |
0000952 |
| Sclerosing cholangitis | 0030991 | |
| Splenomegaly |
Increased spleen size
|
0001744 |
| Thyroiditis |
Thyroid gland inflammation
|
0100646 |
| Ulcerative colitis | 0100279 | |
| Vitiligo |
Blotchy loss of skin color
|
0001045 |
| 1%-4% of people have these symptoms | ||
| Fulminant hepatitis | 0004787 | |
| Hepatocellular carcinoma | 0001402 | |
| Viral hepatitis | 0006562 | |
Diagnosis
Diagnosis of AIH can be complex, and is frequently completed after going through several steps. This includes meeting with your doctor to discuss your past medical problems, your current symptoms, a complete physical exam, blood work, and a liver biopsy.
Clinical Testing and Work-Up
Initial bloodwork will include checking for signs of liver inflammation, liver function, autoimmune markers, and other blood tests to rule out other causes of liver disease.
The inflammation tests will include checking the liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyltranspeptidase (GGT).
Liver function is accessed by checking prothrombin time (PT) and international normalized ratio (INR). These tests can show if you are likely to bleed too much which can happen if the liver is damaged and is not working very well. Albumin is also checked. This is a protein that the liver makes and if it is low it can indicate you may have cirrhosis. Total bilirubin also is completed along with other liver tests. Increased bilirubin may indicate severe inflammation associated with the disease, but may also indicate decreased liver function.
Autoimmune markers that will be checked to include the antinuclear antibody (ANA), smooth muscle antibody (ASMA), liver kidney microsomal antibody (LKM), and immunoglobulin G (IgG). Many autoimmune diseases will cause an elevated ANA and IgG so if those are elevated it does not mean you have AIH, just that you may be more likely to have an autoimmune condition. ASMA and LKM are more specific to AIH when they are elevated alongside elevated liver tests.
Other bloodwork to help make sure that you do not have any other liver disease that could be presenting with similar symptoms to AIH include checking for viral hepatitis (hepatitis, A, B, C, D, E), Wilsons disease (ceruloplasmin levels), hemochromatosis (complete blood count panel (CBC) and anemia panel), alpha1-antitrypsin deficiency (measure alpha 1-antitryspin levels), and alcohol levels in the blood.
A liver biopsy is done to help confirm autoimmune hepatitis and also to stage the amount of fibrosis present. This procedure involves you lying on a table and having part of the right abdomen numbed. The doctor then passes a needle into to the liver. The liver tissue is sent to a pathologist who looks at the sample under a microscope and does special staining to further examine it. A liver biopsy may not completely exclude or confirm AIH. This procedure is typically done as a same day procedure and usually you get to go home 4-5 hours after the test.
A fibroscan is sometimes done between liver biopsies to help quantify the amount of liver fibrosis and fat in the liver or to get an initial idea of how healthy the liver is, but the liver biopsy is the best current test.
Treatment
Medications that may be used initially (“induction therapy”) include :[1][6]
- Corticosteroids (such as prednisone).
- Azathioprine (often in combination with corticosteroids).
- Other immune system suppressants – particularly when treatment with corticosteroids and azathioprine is not effective or causes severe side effects. Examples include mycophenolate mofetil, cyclosporine, or tacrolimus.
Those with AIH are usually started on corticosteroids and then placed on other immunosuppressive agents. Most physicians target a goal either to completely stop the steroids or taper them down to the lowest dose possible as the disease gets into remission. Most people will stay on an immunosuppressant for life because without one the disease relapse rate is >80%. If you have a relapse or flare (liver tests increase while on therapy) then steroids are either restarted or the dose is increased if you are already taking them. Everyone does not necessarily tolerate or respond to the same treatment, so your doctor will have to determine what works best for you. With these medications, your risk of infection is higher because the immune system is being suppressed. The current medication options will be reviewed below.
Corticosteroids such as prednisone, prednisolone, or budesonide are usually used to help suppress the immune system (so the liver is not attacked) and calm down the inflammation in the liver. Prednisone is a common first treatment. It has been used for many years and tends to work for many. Unfortunately, there are several side effects of these medications including bone loss (osteoporosis), high blood sugar, increased appetite, insomnia, mood changes, muscle pain, depression, and anxiety. Budesonide tends to have fewer of the side effects, but has been less studied.
Azathioprine (Imuran) is commonly started during the tapering of prednisone. This medication tends to have less severe side effects compared to the prednisone so it is usually the drug of choice for long-term use. Nausea and vomiting occur in 10-15% of people taking azathioprine; therefore, an alternative treatment is used if it is too severe. There is an increased risk of lymphoma with this medication. Some people are unable to metabolize this medication which can be determined with some additional blood tests. While on this medication, white blood cell counts need to be monitored.
Mycophenolate mofetil (Cellcept) is another option if one cannot tolerate azathioprine. It can also cause a significant amount of GI symptoms including abdominal pain, nausea, vomiting, diarrhea, constipation, and anorexia. Some may also have their kidney function affected by this medication so that must be monitored by bloodwork. Females of childbearing age must take a pregnancy test prior to starting this medication and use two forms of birth control while on the medication because it is associated with birth defects. Breastfeeding must be avoided until 6 months after this medication has been stopped because it is unknown if it is excreted in the breast milk.
Cyclosporine, sirolimus (Rapamune), and tacrolimus (Prograf) are other alternative treatments to azathioprine and mycophenolate mofetil. These medications can also lead to nausea, diarrhea, constipation, abdominal pain, high blood pressure, elevated cholesterol, joint pain, diabetes, and gingivitis.
It is important for patients to adopt a healthy diet and exercise routine to obtain an ideal body weight. The best diet to follow is one with a minimal amount of processed food and high in lean protein, vegetables, and fruits. Those that are overweight can have an increased risk of fatty liver disease and worse outcomes.
