Liver and intrahepatic bile ducts-nontumor
Hepatitis - noninfectious
Autoimmune hepatitis (AIH)

Author: Anthony W.H. Chan, BMedSc, MBChB, FRCPA (see Authors page)

Revised: 30 December 2016, last major update June 2015

Copyright: (c) 2003-2016, PathologyOutlines.com, Inc.

PubMed Search: Autoimmune hepatitis [title] liver
Cite this page: Autoimmune hepatitis. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/liverautoimmune.html. Accessed January 18th, 2017.
Definition / General
  • Chronic self-perpetuating inflammatory liver disease of unknown cause mainly occurring in females of all ages and ethnic groups (J Hepatol 2015;62:S100)
Terminology
  • Previously known as lupoid hepatitis
Epidemiology
  • Incidence is highest in North American (42.9 / 100,000), followed by Europe (10.7-23.9 / 100,000) (J Gastroenterol Hepatol 2015;30:1230)
  • Female predominance with female to male ratio of 4-6:1
  • Usual age of presentation 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 (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
  • 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 syndrome, vitiligo or ulcerative colitis (J Hepatol 2015;62:S100)
  • The incidence of cirrhosis at presentation varies widely: North America (59-85%), Middle East (22.2-45.5%), China (24.8%), Japan (6.4-12.8%) (J Gastroenterol Hepatol 2015;30:1230)
  • "Burnt-out" AIH is one of the most common causes of cryptogenic cirrhosis (Scand J Gastroenterol 2010;45:60)
Diagnosis
  • The diagnosis is based on combinations of clinical, laboratory and histological features
  • Revised diagnostic International Autoimmune Hepatitis Group (IAHG) scoring system (J Hepatol 1999;31:929):
    • Complex system evaluating 11 clinical, laboratory and histological factors
    • For research purposes - not designed for clinical practice
  • Simplified diagnostic IAHG scoring system (Hepatology 2008;48:169):
    • Simple system evaluating 4 laboratory and histological factors: serum autoantibodies, IgG, liver histology and viral hepatitis serology
    • Cutoff values for probable and definite AIH are 6 points (88% sensitivity and 97% specificity) and 7 points (81% sensitivity and 99% specificity), respectively
  • AIH subtypes depend on autoantibody serology:
    • Type 1: positive for antinuclear antibody (ANA) or anti-smooth muscle antibody (SMA); 10% have other autoimmune disorders
    • Type 2: positive for anti-liver-kidney-microsomal (LKM) antibody or anti-liver cytosol type 1 (LC1) antibody positive; often presents with acute or fulminant hepatitis; 17% have other autoimmune disorders
  • About 10% of AIH shows coexisting features of immune mediated biliary disease (overlap syndrome) or are associated with atypical features (variant syndrome)
    • Overlap syndrome: AIH-primary biliary cirrhosis and AIH-primary sclerosing cholangitis
    • Variant syndromes: seronegative AIH and antimitochondrial antibody (AMA)-positive AIH
Laboratory
  • Serum autoantibodies (J Autoimmun 2013;46:17):
    • ANA: positive in 75% of type 1 AIH; not associated with disease course or outcome
    • Anti-SMA: positive in 95% of type 1 AIH; not associated with disease course or outcome
    • Anti-LKM: diagnostic for type 2 AIH; associated with younger age at presentation, fulminant hepatic failure and partial IgA deficiency
    • Anti-LC1: diagnostic for type 2 AIH; associated with more severe inflammation and rapid progression to cirrhosis
    • Anti-soluble liver antigen (SLA) / live-pancreas (LP): positive in 20-50% of AIH; associated with more severe disease, treatment dependence, relapse after drug withdrawal and need for transplantation
  • Serum immunoglobulin G (IgG): not only a diagnostic marker but also a marker for monitoring treatment response (Hepatology 2010;51:2193)
Prognostic Factors
  • Associated with poor clinical outcome: extreme age (≤ 20 years or ≥ 60 years), failure to normalize ALT within 6 months of onset of therapy, serum albumin ≤ 35 g/L (J Gastroenterol Hepatol 2015;30:1230)
Case Reports
Treatment
  • Corticosteroids alone or with azathioprine to achieve normalization of serum transaminase and IgG
  • If no response, add other immunosuppressants (e.g. cyclosporine, tacrolimus or mycophenolate mofetil) and consider liver transplantation
  • Good long term prognosis with 10 year survival rate of 80-100% (J Gastroenterol Hepatol 2015;30:1230, Hepatology 2010;51:2193)
Clinical Images

Images hosted on PathOut server:

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Multiple hypoechoic lesions

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Multiple hypodense liver lesions

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Diffuse gray-white plaque

Micro Description
  • Typical morphological changes:
    • Portal plasma cell rich inflammation
    • Interface hepatitis, formerly referred to as piecemeal necrosis: portal inflammatory cells eroding through the limiting plate between the portal tract and liver parenchyma
    • Emperipolesis: apparent engulfment of lymphocytes by hepatocytes
    • Hepatocyte rosette formation
    • Variable fibrosis (about 10% of AIH does not show any fibrosis at initial presentation)
    • Lobular necroinflammatory activity: usually accompanied by portal and periportal inflammation
  • Uncommon morphological changes:
    • Perivenular necrosis: present in up to 17% of AIH with or without typical portal and periportal changes; usually associated with more severe disease activity and lower histological stage
    • Intrahepatic cholestasis (bilirubinostasis)
    • Syncytial multinucleated giant cells: AIH is the most common cause (30%) of postinfantile giant cell hepatitis, which is rare in adults (0.1-0.25% of all hepatitis) (Hepat Res Treat 2013;2013:601290)
    • Mild bile duct injury: present up to 24% of classical AIH (Hepatology 2001;34:659)
    • Chronic biliary disease or overlap syndrome only need to be considered in the presence of more extensive bile duct injury, florid duct lesion, ductular reaction, ductopenia, chronic cholate stasis, portal granulomas or periductal fibrosis
Micro Images

Images hosted on other servers:

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Interface hepatitis

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Portal inflammation

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Histological features

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Dense portal lymphoplasmacytic infiltrate



Images courtesy of Anthony W.H. Chan, BMedSc, MBChB, FRCPA:

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Rosettes

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PV necrosis

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Portal plasma and IH


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Lobular infiltration

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Giant cell

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Emperipolesis

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Cholestasis

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Bile duct injury

Differential Diagnosis