AIH is a chronic inflammation of the liver caused by an immune reaction against the tissues of the host.
This anomalous immune reaction is found to be the major pathological mechanism, even though the primary event triggering the disease remains to be defined. Probably a genetically determined background for autoimmunity, interacting with other outside and/or environmental factors (i.e., viruses, toxins, drugs, etc.), induces the disease. In fact AIH is associated with the HLA class II : B8, DR3 and DR4 [1][2].
This autoimmune disease causes a chronic liver injury and therefore can lead to liver cirrhosis if not treated.
AIH occurs primarily in woman (about 70% of reported cases) between the ages of 15 and 40 [1].
 

Clinical manifestations

• fatigue
• jaundice
• itching
• enlarged liver
• abdominal discomfort
• aching joints

• chronic fluctuating course (most common) : disease's activity vary during the time
• acute hepatitis
• fulminant hepatitis (rare)
• subclinical course : the disease evolves with mild or without symptoms

Diagnosis

Transaminases (ALT and AST) : are generally increased(3- to 10-fold). They reflect liver cells injury.
Serum proteins electrophoresis : serum gamma globulin can be increased (2-fold). It's characteristic of type I AIH
Autoantibodies (ANA, ASMA, LKM-1): they are frequently positive at high titre (above 1:40), but they could be negative at the onset of the disease.
 

Classification

1. Type 1

Is the more frequent type of AIH and is commonly seen in youngh to middle-aged women.
ANA and/or ASMA and sometimes ANCA are positive. Serum globuline levels are increrased.
2. Type 2

Is more frequent in children. LKM-1 are positive. ANCA are always negative. It can be divided into 2 subtypes:
1. Type IIa : occurs in youngh women. Serum globulin levels are high. It respond to steroid treatment.
2. Type IIb : occurs in older men and is associated with HCV infection. Serum globulin levels are normal. It responds to interferon treatment.
3. Type 3

SLA is positive.

Treatment

a) Immunosuppressive therapy

1) Corticosteroids (prednisone, prednisolone)
They are immunosuppressive and anti-inflammatory drugs.
They take effect quickly, causing a reduction of transaminase levels. Therefore initial therapy should always include corticosteroids. However they have a lot of side effects (obesity, osteoporosis, ulcers, diabetes, high blood pressure), that are dose-dependent. Therefore, when transaminase levels start to fall, the doses of corticosteroids should be reduced [2] and when a response cannot by achieved with corticosteroids alone, it's best to associate them to other drugs, like azthioprine, instead of increasing their doses.
Joints inflammation is the most common side effect reported after reducing treatment dosage [3].
2) Azathioprine
It's an immunosuppressive drug.
It takes several weeks to work, therefore it should be associated with corticosteroids in the initial therapy. Adding azathioprine can also help to keep the required dose of corticosteroids low, particularly when a long term therapy is required, reducing the incidence of their side effects [3].
Patients who cannot tolerate this drug or don't achieve a complete response, can be treated with cyclophosphamide or with cyclosporine.
3) Ursodeoxycholic acid (UDCA)
UDCA can reduce inflammation and liver damage (transaminases and autoantibody levels decrease). It's essentially free of side-effects and therefore can be used for long-term treatment.
Dosage : 500 mg twice daily.

b) Liver transplant
It's required if end-stage liver disease develops. In fact liver, cirrhosis can sometimes developes in some patients despite their apparent and initial response to treatment. Recurrence of autoimmune hepatitis after transplant is possible.
 
 

References

- [1] Harrison et al. (eds.): "Harrison's Principles of Internal Medicine". 12th edition, McGraw-Hill Inc., New York
- [2] Autoimmune Hepatitis. Karl-Hermann Meyer zum Buschenfelde, Ansgar W. Lohse. N Engl J Med 1995; 333(15)
- [3] Azathioprine for long-term maintenance of remission in autoimmune hepatitis. Johnson PJ, McFarlane IG, Williams R.  N Engl J Med 1995; 333: 958-963
- Drug therapy in the management of type 1 autoimmune hepatitis. Czaja AJ. DRUGS 1999; 57(1): 49-68
- Efficacy of ursodeoxycholic acid in Japanese patients with type 1 autoimmune hepatitis. Nakamura K, Yoneda M, Yokohama S, Tamori K, Sato Y, Aso K, Aoshima M, Hasegawa T, Makino I. J Gastroenterol Hepatol 1998; 13(5): 490-495