Autoimmune hepatitis, formerly called lupoid hepatitis, is a chronic, autoimmune disease of the liver that occurs when the body's immune system attacks liver cells, causing the liver to be inflamed. Common initial symptoms include fatigue or muscle aches or signs of acute liver inflammation including fever, jaundice, and right upper quadrant abdominal pain. Individuals with autoimmune hepatitis often have no initial symptoms and the disease is detected by abnormal liver function tests.
|Micrograph showing a lymphoplasmacytic interface hepatitis—the characteristic histomorphologic finding of autoimmune hepatitis. Liver biopsy. H&E stain.|
|Symptoms||Often asymptomatic, fatigue, right upper abdominal pain, anorexia, nausea, jaundice, joint pain, rash|
|Usual onset||40-50 years of age|
|Types||Type 1, type 2, type 3, seronegative|
|Risk factors||Female gender, additional autoimmune disease|
|Diagnostic method||Liver biopsy|
|Differential diagnosis||Primary biliary cholangitis |
Primary sclerosing cholangitis
|Frequency||Incidence 1-2 per 100,000 per year |
Prevalence 10-20 per 100,000
Anomalous presentation of MHC class II receptors on the surface of liver cells, possibly due to genetic predisposition or acute liver infection, causes a cell-mediated immune response against the body's own liver, resulting in autoimmune hepatitis. This abnormal immune response results in inflammation of the liver, which can lead to further symptoms and complications such as fatigue and cirrhosis. The disease may occur in any ethnic group and at any age, but is most often diagnosed in patients between age 40 and 50.
Signs and symptomsEdit
People usually present with one or more nonspecific symptoms, sometimes of long lasting duration, as fatigue, general ill health, lethargy, weight loss, mild right upper quadrant pain, malaise, anorexia, nausea, jaundice or joint pain (arthralgia), especially affecting the small joints. Rarely, rash or unexplained fever may appear. In women, the absence of menstruation (amenorrhoea) is a frequent feature. Physical examination may be normal, but it may also reveal signs and symptoms of chronic liver disease. Many people have only laboratory abnormalities as their initial presentation, as unexplained increase in transaminases and are diagnosed during an evaluation for other reasons. Others have already developed cirrhosis at diagnosis. Of note, alkaline phosphatase and bilirubin are usually normal.
60% of patients have chronic hepatitis that may mimic viral hepatitis, but without serologic evidence of a viral infection. The disease is strongly associated with anti-smooth muscle autoantibodies. There is currently no conclusive evidence as to any specific cause.
The diagnosis of autoimmune hepatitis is best achieved with a combination of clinical, laboratory, and histological findings after excluding other etiological factors (e.g. viral [such as the Epstein-Barr virus], hereditary, metabolic, cholestatic, and drug-induced liver diseases). The requirement for histological examination necessitates a liver biopsy, typically performed with a needle by the percutaneous route, to provide liver tissue.
A number of specific antibodies found in the blood (antinuclear antibody (ANA), anti-smooth muscle antibody (SMA), anti-liver kidney microsomal antibodies (LKM-1, LKM-2, LKM-3), anti soluble liver antigen (SLA), liver–pancreas antigen (LP), and anti-mitochondrial antibody (AMA)) are of use, as is finding an increased immunoglobulin G level. The presence of anti-mitochondrial antibody is more suggestive of primary biliary cholangitis.Hypergammaglobulinemia is also of diagnostic value.
Histological features supportive of a diagnosis of autoimmune hepatitis include:
- A mixed inflammatory infiltrate centered on the portal tract
- The inflammatory infiltrate may breach the interface between the portal tract and liver parenchyma: so-called interface hepatitis
- The most numerous cell in the infiltrate is the CD4-positive T cell.
- Plasma cells may be present within the infiltrate. These are predominantly IgG-secreting.
- Eosinophils may be present within the infiltrate.
- Emperipolesis, where there is penetration of one cell through another, within the inflammatory infiltrate
- Varying degrees of necrosis of periportal hepatocytes.
- In more severe cases, necrosis may become confluent with necrotic bridges forming between central veins.
- Hepatocyte apoptosis manifest as acidophils or apoptotic bodies.
- Rosettes of regenerating hepatocytes.
- Any degree of fibrosis from none to advanced cirrhosis
- Biliary inflammation without destruction of biliary epithelial cells in a minority of cases.
Expert opinion has been summarized by the International Autoimmune Hepatitis Group, which has published criteria which utilize clinical, laboratory, and histological data that can be used to help determine if a patient has autoimmune hepatitis. A calculator based on those criteria is available online.
Four subtypes of autoimmune hepatitis are recognised, but the clinical utility of distinguishing subtypes is limited.
- Type 1 AIH. Positive ANA and SMA, elevated immunoglobulin G (classic form, responds well to low dose steroids);
- Type 2 AIH. Positive LKM-1 (typically female children and teenagers; disease can be severe), LKM-2 or LKM-3;
- Type 3 AIH. Positive antibodies against soluble liver antigen (this group behaves like group 1) (anti-SLA, anti-LP)
- AIH with no autoantibodies detected (~20%) (of debatable validity/importance)
Treatment may involve the prescription of immunosuppressive glucocorticoids such as prednisone, with or without azathioprine, and remission can be achieved in up to 60–80% of cases, although many will eventually experience a relapse. Budesonide has been shown to be more effective in inducing remission than prednisone, and result in fewer adverse effects. Those with autoimmune hepatitis who do not respond to glucocorticoids and azathioprine may be given other immunosuppressives like mycophenolate, ciclosporin, tacrolimus, methotrexate, etc. Liver transplantation may be required if patients do not respond to drug therapy or when patients present with fulminant liver failure.
Autoimmune hepatitis is not a benign disease. Despite a good initial response to immunosuppression, recent studies suggest that the life expectancy of patients with autoimmune hepatitis is lower than that of the general population. Additionally, presentation and response to therapy appears to differ according to race. For instance, African Americans appear to present with a more aggressive disease that is associated with worse outcomes. If untreated, the mortality rate for severe autoimmune hepatitis may be as high as 40 percent.
Outcomes with liver transplant are generally favorable, with a five-year survival greater than 80 percent.
The disease may occur in any ethnic group and at any age, but is most often diagnosed in patients between age 40 and 50.
Autoimmune hepatitis was previously called "lupoid" hepatitis. It was originally described in the early 1950s.
Most patients do have an associated autoimmune disorder such as systemic lupus erythematosus. Thus, its name was previously lupoid hepatitis.
Because the disease has multiple different forms, and is not always associated with systemic lupus erythematosus, lupoid hepatitis is no longer used. The current name at present is autoimmune hepatitis (AIH).
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