Autoimmune Hepatitis

Autoimmune hepatitis - cropped - very high mag[1]


Presentation

Oettinger et al. published a series of 142 children with autoimmune hepatitis [8]. Findings included:

Other symptoms and signs may include:

Workup

Work up consists of a detailed history and physical examination.

Laboratory Tests

  • Complete blood count
  • Liver function tests
  • Serology for ANAs, SMAs, LKM1, anti-LC1
  • Immunoglobulins and albumen levels
  • Blood profile

Imaging Studies

Test Results

Test results will indicate eosinophilia, raised ANA, ASMA and other increased antibody titres. Blood profile will show increased blood count and a prolonged prothrombin time. Biopsy will show Ag-Ab aggregates in the liver. CT scan will show extrahepatic involvement, if any.

Treatment

Medications

Corticosteroids are the mainstay of treatment. Budesonide has been shown to be more effective in inducing remission than prednisone, and results in fewer adverse effects [9].

Transplantation

Liver transplantation may be required if patients do not respond to drug therapy or when patients present with fulminant liver failure.

Prognosis

Autoimmune hepatitis may advance to cirrhosis [3]. Without treatment, almost 50% of patients will die within five years. Mild liver disease generally has a good prognosis with treatment, however, the more severe the disease, the worst the prognosis. In severe and/or complicated disease, life expectancy is greatly reduced.

Complications

Untreated and uncontrolled autoimmune hepatitis may progress to chronic hepatitis that will then show widely systemic manifestations. Complications include the following:

Etiology

Autoimmune hepatitis is an inflammation of the liver that occurs when immune cells mistake the liver's normal cells for harmful invaders and attack them [3]. The exact cause of the disease is unknown, but a number of factors have been implicated in its development. It may be initiated or triggered by genetic factors, viral infections (eg acute hepatitis A and B, Epstein-Barr virus infection) [4], etc. Some chemical factors such as interferons, etc may also play a role.

Genetic factors are proposed to be the main culprit behind this disease. DR3, DR4, B8, B15 and C4A gene deletions and mutations may lead to the production of autoantibodies. To some point, the body will be able to combat these autoantibodies but when an environmental trigger, such as infection by a virus, etc may cause the threshold of tolerance to be breached, then the disease becomes symptomatic.

Epidemiology

Incidence

0.1-1.2 cases per 100,000 people are estimated to suffer from autoimmune hepatitis in the United States. 6% of all liver transplantations conducted in the US are due to this disease.

Age

It may occur at any age, ranging from infants to old people. Some studies reveal a bimodal age prevalence, with peak incidence first in the mid-second to early-third decade of life and second peak incidence between the late-fourth to seventh decade of life.

Sex

Women are affected more often than men (70% to 80% of patients are women) [2].

Sex distribution
Age distribution

Pathophysiology

Microscopically, clusters of plasma cells in the interface of portal tracts and hepatic lobules are fairly characteristic for autoimmune hepatitis [5]. The salient features [6] include the absence of serologic markers of viral infection, elevated serum IgG and gamma-globulin levels (1-2-3x normal), and high serum titres of autoantibodies.

Subtypes

Type I

It is characterised by presence of positive ANA and ASMA [7] antibodies. Anti-actin antibodies may also be present. Gamma globulin levels are greatly elevated. This type occurs predominantly in elderly patients. HLA associations include DR3, DR4 and B8.

Type II

It is characterised by presence of Anti-LKM (anti-liver kidney microsomal antibody) and P450 IID6 antibodies. It occurs most commonly in young girls , and is very rare in adults. HLA associations include DR3, B14 and C4AQO.

Type III

This subtype occurs most commonly in middle-aged adults and is characterised by elevated levels of cytokeratin 8 and 18. Soluble liver-kidney antigens are also present. HLA association is unclear.

Prevention

Since the exact etiology is unknown, this disease can not be prevented. However, by taking appropriate treatment of other autoimmune disease such as autoimmune thyroiditis, Grave's disease, proliferative glomerulonephritis, rheumatoid arthritis, etc the autoimmune factors leading to this disease may be controlled.

Summary

Autoimmune hepatitis is a chronic and progressive hepatitis of unknown etiology [1]. It is a type of inflammation of the liver which occurs due to production of autoantibodies that target the normal cells of the liver and destroy them, leading to an inflammatory cascade that further damages the liver and symptoms of liver disease appear. These symptoms may vary from those of mild liver disease to those of liver failure in severe cases.

Patient Information

Autoimmune hepatitis is a disease resulting in inflammation of the liver due to autoantibodies produced by the body itself. This type of hepatitis is different from viral hepatitis, in terms of mode of transmission, pathophysiology and prognosis. If you are suffering from other autoimmune disease, you may be more at risk for developing this form of hepatitis. It is therefore, recommended to regularly visit your physician for routine tests and work up.

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References

  1. Krawitt EL: Autoimmune Hepatiti. N Engl J Med 354:54, 2006
  2. McFarlane IG, Heneghan MA. Autoimmunity and the Female Liver. Hepatol Res. April 2004;28(4):171-176. [Medline]
  3. Czaia AJ. Autoimmune Hepatitis. In: Feldman M, Friedman LS, Brandt LJ, eds. Sleisenger and Fordtran's Gastrointestinal and Liver Disease. 9th edition. Philadelphia. Pa: Saunders Elsevier;2010: Chap 88
  4. Vento S, Cainelli F. Is there a role for viruses in triggering autoimmune hepatitis? Autoimmune Rev. Jan 2004;3(1):61-9
  5. Czaja AJ:Autoimmune Liver Disease. Curr Opin Gastroenterol 23:255, 2007
  6. Robbins and Cotran, Pathologic Basis of Disease. 8th ed. Pa: Saunders Elsevier. Chap 17. pg 855-56
  7. Bogdanos DP, Invernizzi P, Mackay IR, Vergani D (June 2008). Autoimmune Liver Serology:Current Diagnostic and Clinical challenges. World J Gastroenterol. 14(21):3374-3387 doi 10.3748/wjg.14.3374 PMC 2716592 
  8. Oettinger R, Brunnberg A, Gerner P, Wintermeyer P, Jenke A, Wirthe S. Clinical features and biochemical data of Caucasian children at diagnosis of autoimmune hepatitis. J Autoimmune. Feb 2005;24(1):79-84 
  9. Mann MP, Strassburg, CP (2011). Therapeutic Strategies for Autoimmune Hepatitis. Digestive Strategies. Basel, Switzerland. 29(4):411-5. 
  10. Stephen J McPhee, Maxine A Papadakis. Current Medical Diagnosis and Treatment 2009. Pg 596

Media References

  1. Autoimmune hepatitis - cropped - very high mag, CC BY-SA 3.0

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