Autoimmune Hepatitis

The disease is related to the following processes:  auto-immune and has an incidence of about  8 / 100.000.

Overview

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.

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.

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:

Presentation

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

  • Jaundice 58%
  • Non specific weakness 57%
  • Anorexia 47%
  • Abdominal pain 38% 
  • Paleness 26%

Other symptoms and signs may include:

  • General discomfort or uneasiness 
  • Abdominal distension
  • Pruritis
  • Diarrhea
  • Edema
  • Weight loss
  • Spider angiomata
  • Hepatomegaly
  • Splenomegaly
  • Portal hypertension (advanced cases)
  • CNS involvement (advanced cases)

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

  • Liver biopsy
  • CT scan

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.

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.

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

  • Acute hepatitis, autoimmune hemolytic anemia, and erythroblastocytopenia induced by ceftriaxone - F Longo, P Hastier, MJM Buckley - The American journal of , 1998 - Elsevier
  • Cytoplasmic antibody in inflammatory bowel and hepatobiliary diseases. High prevalence in ulcerative colitis, primary sclerosing cholangitis, and autoimmune hepatitis - S Hardarson, DR Labrecque, FA Mitros - American journal of , 1993 - ukpmc.ac.uk
  • Abnormal findings on liver function tests - DV Gopal, HR Rosen - Postgrad Med, 2000 - postgradmed.org
  • And poor outcome in type I autoimmune hepatitis: role of cirrhosis development, patterns of transaminases during remission and plasma cell activity in the liver biopsy - S Verma, B Gunuwan, M Mendler - The American journal of , 2004 - nature.com
  • In chronic active liver disease. I. Lymphocyte subsets in liver biopsies of patients with untreated idiopathic autoimmune hepatitis, chronic active hepatitis B and primary - HF Eggink, HJ Houthoff, S Huitema - Clinical and , 1982 - ncbi.nlm.nih.gov
  • An" autoimmune" reaction against human tissue antigens in certain acute and chronic diseases: I. Serological investigations - DC GAJDUSEK - Archives of Internal Medicine, 1958 - Am Med Assoc
  • 'Acute'Autoimmune Hepatitis - RM Crapper, PS Bhathal, IR Mackay, IH Frazer - Digestion, 1986 - content.karger.com
  • Autoantibodies and autoantigens in autoimmune hepatitis - CP Strassburg, MP Manns - Seminars in liver disease, 2002 - gidiv.ucsf.edu
  • Association of autoimmune hepatitis with HLA‐Bw54 and DR4 in Japanese patients - T Seki, K Kiyosawa, H Inoko, M Ota - Hepatology, 2005 - Wiley Online Library
  • Leukocyte antigen-DQB1* genotypes encoding aspartate at position 57 are associated with 3β-hydroxysteroid dehydrogenase autoimmunity in premature ovarian - S Arif, JA Underhill, P Donaldson - Journal of Clinical , 1999 - Endocrine Soc
  • Collagen diseases: pathologic study of 160 cases with particular reference to hepatic arteritis, primary biliary cirrhosis, autoimmune hepatitis and nodular regenerative - , N Sato, H Abe, Y Aoki, T Hoshi, H Hashimoto - Liver, 2000 - Wiley Online Library
  • 2 The Past Medical History, Social History, and Review of Systems - A Illnesses - Springer
  • Autoimmune hepatitis type 1: safety and efficacy of prolonged medical therapy - S Seela, H Sheela, JL Boyer - Liver International, 2005 - Wiley Online Library
  • And poor outcome in type I autoimmune hepatitis: role of cirrhosis development, patterns of transaminases during remission and plasma cell activity in the liver biopsy - S Verma, B Gunuwan, M Mendler - The American journal of , 2004 - nature.com
  • Acute hepatitis E virus infection presenting as a prolonged cholestatic jaundice - L Mechnik, N Bergman, M Attali - Journal of clinical , 2001 - journals.lww.com
  • Autoimmune hepatitis - EL Krawitt - New England Journal of Medicine, 1996 - Mass Medical Soc
  • Autoimmune hepatitis - EL Krawitt - New England Journal of Medicine, 2006 - Mass Medical Soc
  • Aplastic anemia complicating orthotopic liver transplantation for non-A, non-B hepatitis - AG Tzakis, M Arditi, PF Whitington - England Journal of , 1988 - Mass Medical Soc
  • A comparison of the efficacy and safety of lymecycline and minocycline in patients with moderately severe acne vulgaris - WJ Cunliffe, E Grosshans, S Belaich - European Journal of , 1998 - jle.com
  • Antibodies to soluble liver antigen/liver pancreas and HLA risk factors for type 1 autoimmune hepatitis - AJ Czaja, PT Donaldson, AW Lohse - The American journal of , 2002 - nature.com
  • Allelic sequence variation in the HLA class II genes and proteins in patients with autoimmune hepatitis - DG Doherty, PT Donaldson, JA Underhill - , 2005 - Wiley Online Library
  • A phospholipid-β2-glycoprotein I complex is an antigen for anticardiolipin antibodies occurring in autoimmune disease but not with infection - JE Hunt, HP McNeil, GJ Morgan, RM Crameri, SA Krilis - Lupus, 1992 - lup.sagepub.com
  • A 10 year follow up study of patients transplanted for autoimmune hepatitis: histological recurrence precedes clinical and biochemical recurrence - JC Duclos-Vallee, M Sebagh, K Rifai, C Johanet - Gut, 2003 - gut.bmj.com
  • Liver disease. I. Lymphocyte subsets in liver biopsies of patients with untreated idiopathic autoimmune hepatitis, chronic active hepatitis B and primary biliary cirrhosis. - HF Eggink, HJ Houthoff, S Huitema - Clinical and , 1982 - ncbi.nlm.nih.gov
  • Cytoplasmic antibody in inflammatory bowel and hepatobiliary diseases. High prevalence in ulcerative colitis, primary sclerosing cholangitis, and autoimmune hepatitis - S Hardarson, DR Labrecque, FA Mitros - American journal of , 1993 - ukpmc.ac.uk
  • A role for hepatitis C virus infection in type II cryoglobulinemia - V Agnello, RT Chung, LM Kaplan - New England Journal of , 1992 - Mass Medical Soc
  • Autoimmune hepatitis - MP Manns, A Schüler - 2004 - books.google.com
  • Lymphoproliferative disorders in Sjögren's syndrome present a restricted use of antigen receptor gene segments similar to those used by hepatitis C virus‐associated - V De Re, S De Vita, D Gasparotto - European journal of , 2002 - Wiley Online Library
  • Acute liver biopsy lesions in early autoimmune (“lupoid”) chronic active hepatitis - JH Lefkowitch, TF Apfelbaum, L Weinberg, G Forester - Liver, 2008 - Wiley Online Library
  • Chronic autoimmune thyroiditis - CM Dayan, GH Daniels - New England journal of medicine, 1996 - Mass Medical Soc
  • Atypical clinical manifestations of hepatitis A - ER Schiff - Vaccine, 1992 - Elsevier
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