Liver and intrahepatic bile ducts-nontumor

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Liver and intrahepatic bile ducts-nontumor

Hepatitis - noninfectious

Autoimmune hepatitis

Reviewers: Komal Arora, M.D. (see Reviewers page)
Revised: 2 May 2012, last major update May 2012
Copyright: (c) 2004-2012, PathologyOutlines.com, Inc.

General
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● Formerly called lupoid hepatitis
● Indolent or severe
● 70% women, usually ages 20-45 years
● A diagnosis of exclusion
● Associated with HLA-B8 or HLA-DRw3
● 60% have other autoimmune disorders (rheumatoid arthritis, thyroiditis, Sjogren’s syndrome, ulcerative colitis)
● Symptoms: amenorrhea, arthralgias, symptoms of chronic hepatitis (eMedicine)

Laboratory
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● Viral markers negative, elevated IgG, high ALT and AST (300-500 mg/dl)

Antinuclear antibody: 80% have ANA > 1:80, but ANAs also present in 60% with primary biliary cirrhosis, 50% with alcohol related liver disease, 40% with hepatitis B

Anti-smooth muscle actin antibody: 50% sensitive, not specific, often occurs with antinuclear antibodies
● Directed against F-act, part of hepatocyte cytoskeleton, usually > 1:80 vs. low titers in normals
● Indirect fluorescence shows uniform staining of rat stomach muscularis propria, muscularis mucosa and walls of blood vessels but faint staining of glomerular mesangial zones
● Cable-like staining of Hep 2 cells

Anti-liver-kidney-microsomal antibody: 25% sensitive, usually younger patients
● Antibodies to LKMA and CK 8/18
● Rat distal tubules are negative, but hepatocytes and proximal convoluted tubules are positive
● If positive, anti-mitochondrial antibodies are negative
● Confirm LKMA with Western blot
● LKMA is cytochrome P450 component for LKMA-1; LKMA-2 in patients taking ticrynafen (off market), LKMA-3 in patients with delta hepatitis

Anti-mitochondrial antibody: 15%, may be part of overlap syndrome with primary biliary cirrhosis
● Type 1: anti-smooth muscle antibody and antinuclear antibody positive; typically teenager girls or ages 45-70 years
● 10% have other autoimmune disorders such as arthralgias and thyroid disease
● Type 2: anti-liver-kidney-microsomal antibody positive
● More common in children
● Adult cases may represent chronic hepatitis C
● Often presents with acute or fulminant hepatitis
● 17% have other autoimmune disorders
● Type 3: 25% have only antisoluble liver protein antibody
● Negative for ANA and anti-liver-kidney-microsomal antibody
● 75% have anti-smooth muscle antibody or anti-liver membrane antibody
● Usually women, mean age 37 years
● Usually no systemic autoimmune manifestations

Treatment
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● Steroids (dramatic response); failure to respond suggests diagnosis is wrong
● Liver transplantation (Ann Hepatol 2012;11:222)
● Overall, excellent long term prognosis (Hepat Res Treat 2011;2011:390916)

Gross images
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HIV+ woman after HAART treatment

Micro description
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● Dense uniform portal infiltrate with abundance of plasma cells, central vein to portal tract bridging necrosis, extensive piecemeal necrosis, central necrosis with plasma cells, variable eosinophils

Micro images
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Interface hepatitis

HIV+ woman after HAART treatment

Differential diagnosis
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● Hepatitis A, chronic hepatitis C (less severe and more focal interface hepatitis), primary biliary cirrhosis, primary sclerosing cholangitis, overlap syndromes (Ulster Med J 2011;80:15), drug/toxin reaction

Additional references
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● Best Pract Res Clin Gastroenterol 2011;25:689, Ann Hepatol 2005;4:6, Minerva Gastroenterol Dietol 2007;53:43

End of Liver and intrahepatic bile ducts-nontumor > Hepatitis - noninfectious > Autoimmune hepatitis

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