Question 1 of 10

    Autoimmune Hepatitis

    Autoimmune hepatitis - cropped - very high mag[1]

    This disorder originates from the following process: auto-immune.

    Presentation

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

    Other symptoms and signs may include:

    Skin
    Hirsutism
    • . • Endocrine changes like cushingoid appearance, acne , hirsutism. • Pulmonary changes like pleurisy,transitory pulmonary infiltrates and collapse. • Acute,recurrent and non- deforming polyarthrits of large joints. • Mild aneamia, leucopenia, thrombocytopenia[de.slideshare.net]
    • Skin rashes (including acne), hirsutism.[patient.info]
    • Compared to prednisone, it has a relatively safe adverse-effect profile with headache and respiratory infection seen most commonly. 9 Cosmetic changes such as moon face, acne, and hirsutism have been noted. 8 Budesonide is primarily metabolized through[uspharmacist.com]
    • Common symptoms include the following: Fatigue Upper abdominal discomfort Mild pruritus Anorexia Myalgia Diarrhea Cushingoid features Arthralgias Skin rashes (including acne) Edema Hirsutism Amenorrhea Chest pain from pleuritis Weight loss and intense[emedicine.medscape.com]
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  • urogenital
    Amenorrhea
    • Genetic predisposition: North America / Europe: HLA-DR3 (DRB1*0301) and HLA-DR4 (DRB1*0401) China / Japan: HLA-DR4 (DRB1*0405) Clinical features Most patients have nonspecific symptoms: fatigue, anorexia, nausea, weight loss, jaundice, pruritus and amenorrhea[pathologyoutlines.com]
    • Symptoms Symptoms may include: Abdominal distention Dark urine Fatigue General discomfort, uneasiness, or ill feeling ( malaise ) Itching Loss of appetite Nausea or vomiting Pale or clay-colored stools Absence of menstruation (amenorrhea) may also be[scripps.org]
    • Common symptoms include the following: Fatigue Upper abdominal discomfort Mild pruritus Anorexia Myalgia Diarrhea Cushingoid features Arthralgias Skin rashes (including acne) Edema Hirsutism Amenorrhea Chest pain from pleuritis Weight loss and intense[emedicine.medscape.com]
    • […] one or more of the following nonspecific symptoms of varying severity: fatigue, general ill health, mild pain in the right upper quadrant, lethargy, malaise, anorexia, weight loss, nausea, pruritus, jaundice, and arthralgia involving the small joints; amenorrhea[uspharmacist.com]
    • Roughly 20% of patients will be asymptomatic, with elevated transaminases identified on screening examination or during evaluation for amenorrhea, thyroid disease, arthralgia, or diabetes mellitus.[nature.com]
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  • musculoskeletal
    Arthritis
    • ENBREL was first approved in 1998 for moderate-to-severe rheumatoid arthritis.[prnewswire.com]
    • About half the people with type 1 autoimmune hepatitis have other autoimmune disorders, such as celiac disease, rheumatoid arthritis or ulcerative colitis.[mayoclinic.org]
    • By Categories Aquatics Compression Diet and Nutrition Exercise Equipment Hearing Devices Independent Living Low Vision Aids Medical Supplies Pain Relief Parkinsons Pediatrics & Maternity Physical Therapy Skin Care Winter Products Oxygen Shop by Topic Arthritis[activeforever.com]
    Arthralgia
    • Although patients may present with acute symptoms (eg, arthralgia), about 34% to 45% are asymptomatic and are identified subsequent to abnormal liver function tests such as increased alanine and/or aspartate aminotransferase (generally 2,3 Elevated levels[questdiagnostics.com]
    • The patient will sometimes present with jaundice, fever and right upperquadrant pain and occasionally systemic symptoms such as arthralgias (arthritis), myalgias (muscle aches), polyserositits and thrombocytopenia.[texasliver.com]
    • The next most common symptoms are abdominal pain, jaundice, arthralgia, and epistaxis.[clinicaladvisor.com]
    • […] hepatic failure. [4] [5] 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 arthralgia[en.wikipedia.org]
    • In the larger study, the authors retrospectively examined the clinical courses of 31 patients with asymptomatic AIH (25% of their total cohort), which they defined as free of even nonspecific symptoms such as fatigue, arthralgias, and abdominal pain.[healio.com]
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  • Entire body system
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  • Liver, Gall & Pancreas
    Jaundice
    • This leads to decreased liver function, which may cause jaundice.[rileychildrens.org]
    • On physical exam, there was right upper-quadrant tenderness and notable jaundice but no hepato-splenomegaly.[bloodjournal.org]
    • Although the disease is chronic, many patients with autoimmune hepatitis present acutely ill with jaundice, fever and sometimes symptoms of severe hepatic dysfunction, a picture that resembles acute hepatitis.[texasliver.com]
    • Symptoms include jaundice, dark urine, fever and flu­like symptoms.[bshr.com]
    Hepatomegaly
    • CT Nonspecific, ranging from normal to hepatomegaly and cirrhosis.[radiopaedia.org]
    • AIH symptoms include: enlarged liver (hepatomegaly) abnormal blood vessels on the skin ( spider angiomas ) abdominal distention (swelling) dark urine pale-colored stools Additional symptoms may include: yellowing of the skin and eyes ( jaundice ) itching[healthline.com]
    • Signs Common findings on physical examination are as follows: Hepatomegaly.[patient.info]
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  • 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.

    Pathology

    Biopsy
    Liver Biopsy
    • A liver biopsy is important to confirm the diagnosis and provide a prognosis.[hepatitiscentral.com]
    • Liver biopsy: [ 9 ] Liver biopsy is the most important diagnostic procedure in patients with AIH.[patient.info]
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  • Laboratory

    Serum
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  • HLA Type
    HLA-DR3
    • For example, HLA DR3 positivity only contributes when other antibodies are negative.[napervillegi.com]
    • It also usually signifies a decreased response to corticosteroids; however extra-hepatic manifestations are less common in HLA-DR3 serotype associated AIH.[jpma.org.pk]
    • For AIH-2, the primary association is HLA DR3 in Europe and HLA DQ2 and HLA DR7 in Canada.[journal.frontiersin.org]
    • […] depends on subtype: Type 1: bimodal (10 - 25 years and 45 - 70 years) Type 2: 15 years Etiology Etiology unknown; genetic and environmental factors may play roles in pathogenesis ( J Hepatol 2015;62:S100 ) Genetic predisposition: North America / Europe: HLA-DR3[pathologyoutlines.com]
    • […] age 40 years Median age 10 years Presentation Asymptomatic to fulminant More likely to be acute; can have fluctuating course; associated with IgA deficiency Serology ANA, anti SMA Anti LKM 1, anti LC 1 HLA association HLA DR3/DR4 HLA DR3/DR7 Prognosis[bmb.oxfordjournals.org]
    HLA-DR4
    • (DRB1*0401) China / Japan: HLA-DR4 (DRB1*0405) Clinical features Most patients have nonspecific symptoms: fatigue, anorexia, nausea, weight loss, jaundice, pruritus and amenorrhea Up to 25% of patients are asymptomatic, whereas 25 - 30% have episodes[pathologyoutlines.com]
    • HLA-DR3 serotype also occurs more commonly in caucasians. 10,11 HLA-DR4 serotype associated disease occurs more commonly in older adults and usually responds well to immunosuppressive therapy and exhibits more extra-hepatic manifestations. 10,11 HLA-DR4[jpma.org.pk]
    • In contrast, HLA DR4 is the primary association in Japan and Mexico.[journal.frontiersin.org]
    • Race-, sex-, and age-related differences in incidence The disease is most common in whites of northern European ancestry with a high frequency of HLA-DR3 and HLA-DR4 markers.[emedicine.medscape.com]
    • Geographic variations in these factors are seen, with type 1 AIH in Caucasians being associated with HLA-DR3 serotype while in Japan where HLA-DR3 is rare, the primary association is with HLA-DR4.[bmcgastroenterol.biomedcentral.com]
    HLA-B8
    • B8, DR3 haplotype has been associated with a number of autoimmune diseases such as AIH, thyroiditis, celiac disease, and myasthenia gravis.[nature.com]
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  • 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:

    Complications

    Arthritis
    • ENBREL was first approved in 1998 for moderate-to-severe rheumatoid arthritis.[prnewswire.com]
    • About half the people with type 1 autoimmune hepatitis have other autoimmune disorders, such as celiac disease, rheumatoid arthritis or ulcerative colitis.[mayoclinic.org]
    • By Categories Aquatics Compression Diet and Nutrition Exercise Equipment Hearing Devices Independent Living Low Vision Aids Medical Supplies Pain Relief Parkinsons Pediatrics & Maternity Physical Therapy Skin Care Winter Products Oxygen Shop by Topic Arthritis[activeforever.com]
    Jaundice
    • This leads to decreased liver function, which may cause jaundice.[rileychildrens.org]
    • On physical exam, there was right upper-quadrant tenderness and notable jaundice but no hepato-splenomegaly.[bloodjournal.org]
    • Although the disease is chronic, many patients with autoimmune hepatitis present acutely ill with jaundice, fever and sometimes symptoms of severe hepatic dysfunction, a picture that resembles acute hepatitis.[texasliver.com]
    • Symptoms include jaundice, dark urine, fever and flu­like symptoms.[bshr.com]
    Chronic Active Hepatitis
    • Liver biopsy may show mild chronic active hepatitis, more advanced chronic active hepatitis with scarring (fibrosis), or a fully developed cirrhosis.[hepatitiscentral.com]
    • Antigen specific suppressor cell function in autoimmune chronic active hepatitis.[link.springer.com]
    • The prognosis of chronic active hepatitis without cirrhosis in relation to bridging necrosis.[healio.com]
    • This process is similar to any other chronic active hepatitis.[meddean.luc.edu]
    • Autoimmune chronic active hepatitis in Down's syndrome.[down-syndrome.org]
    Ulcerative Colitis
    • Disease Ulcerative colitis Ulcerative colitis is a condition in which the lining of the large intestine (colon) and rectum become inflamed.[scripps.org]
    • ., thyroiditis, diabetes, ulcerative colitis, Coombs-positive haemolytic anaemia, proliferative glomerulonephritis, Sjögren syndrome.[medical-dictionary.thefreedictionary.com]
    • These may include thyroiditis, Grave's disease, type 1 diabetes, and ulcerative colitis.[hopkinsmedicine.org]
    Hashimoto's Thyroiditis
    • People who already have an autoimmune disease, such as celiac disease, rheumatoid arthritis or hyperthyroidism (Graves’ disease or Hashimoto’s thyroiditis), may be more likely to develop autoimmune hepatitis.[mayoclinic.org]
    • AIH is about 4 times more common in females than males and is commonly associated with other autoimmune conditions including type 1 diabetes, Hashimoto's thyroiditis, and celiac disease.[rarediseases.org]
    • ASSOCIATED CONDITIONS • Hashimotos thyroiditis and other thyroid abnormalities like myxoedema and thyrotoxicosis. • Endocrine changes like cushingoid appearance, acne , hirsutism. • Pulmonary changes like pleurisy,transitory pulmonary infiltrates and[de.slideshare.net]
    • Sometimes associated with other autoimmune diseases, such as type 1 diabetes , Hashimoto thyroiditis , pernicious anemia , or Sjögren syndrome The signs and symptoms of hepatitis are the same, regardless of the cause, but they may vary from person to[labtestsonline.org]
    Autoimmune Hemolytic Anemia
    • PATHOGENESIS EVIDENCE SUPPORTING AUTOIMMUNE PATHOGENESIS  Histopathological lesions composed of cytotoxic Tcells and plama cells  Circulating autoantibodies  Hyperglobulinemia  Other autoimmune disorders: thyroiditis, RA , autoimmune hemolytic anemia[de.slideshare.net]
    • Autoimmune hemolytic anemia with giant cell hepatitis: case report and review of the literature.[nature.com]
    Autoimmune Disease
    Primary Biliary Cirrhosis
    • Primary biliary cirrhosis .[nature.com]
    • Qualitative and quantitative differences between bile ducts in chronic hepatitis and in primary biliary cirrhosis .[nature.com]
    • biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) 5.[de.slideshare.net]
    • MRI T2: nonspecific, increased periportal oedema 4 MRCP: primary sclerosing cholangitis (PSC) should be excluded Treatment and prognosis Treatment is similar to other autoimmune conditions, and often uses immunomodulating medications. primary biliary[radiopaedia.org]
    Primary Sclerosing Cholangitis
    Sjogren's Syndrome
    • Some patients have other autoimmune disorders such as thyroiditis, ulcerative colitis, diabetes mellitus, vitiligo (patchy loss of skin pigmentation), or Sjogren’s syndrome (a syndrome that causes dry eyes and dry mouth).[hepatitiscentral.com]
    • If you have AIH, there's a good chance you also have another autoimmune disease , such as Crohn's disease , rheumatoid arthritis , lupus , or Sjogren's syndrome .[webmd.com]
    • For example, patients with other autoimmune diseases — thyroiditis, ulcerative colitis, diabetes mellitus, vitiligo (a patchy loss of pigment in the skin), Sjogren’s syndrome (a condition causing dry eyes and mouth) — are more likely to have autoimmune[gicare.com]
    • […] loss, jaundice, pruritus and amenorrhea Up to 25% of patients are asymptomatic, whereas 25 - 30% have episodes of acute / fulminant hepatitis 50% have concurrent extrahepatic autoimmune disorders, including autoimmune thyroiditis, rheumatoid arthritis, Sjogren[pathologyoutlines.com]
    • These include: Graves disease Inflammatory bowel disease Rheumatoid arthritis Scleroderma Sjogren syndrome Systemic lupus erythematosus Thyroiditis Type 1 diabetes Ulcerative colitis Autoimmune hepatitis may occur in family members of people with autoimmune[scripps.org]

    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.

    Other symptoms

    Toxic Liver Disease
    • […] digestive system K70-K77 2018 ICD-10-CM Range K70-K77 Diseases of liver Type 1 Excludes jaundice NOS ( R17 ) Diseases of liver K75 ICD-10-CM Diagnosis Code K75 Other inflammatory liver diseases 2016 2017 2018 Non-Billable/Non-Specific Code Type 2 Excludes toxic[icd10data.com]
    Antinuclear Autoantibodies
    • Patients with type 1 AIH have anti–smooth muscle and/or antinuclear autoantibodies, whereas type 2 is characterized by the presence of anti–liver kidney microsomal and/or anti–liver cytosol type 1 (LC1) autoantibodies. 1 – 3 Autoantibodies can be positive[pediatrics.aappublications.org]

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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

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