What are the diagnostic criteria and treatment options for autoimmune hepatitis?

Diagnosis of Autoimmune Hepatitis

The diagnosis of autoimmune hepatitis requires a comprehensive panel of tests including liver function tests, immunoglobulins, autoantibodies, and liver biopsy, with histological examination being essential to establish the diagnosis and guide treatment. 1

Diagnostic Criteria

Autoimmune hepatitis (AIH) diagnosis is based on:

1. Clinical and Laboratory Features:

   • Predominantly elevated serum aminotransferases (AST/ALT) 2
   • Alkaline phosphatase to AST ratio <1.5 supports AIH diagnosis 1
   • Hypergammaglobulinemia - IgG levels >1.5 times upper normal limit for definite AIH 2
   • Absence of viral hepatitis markers 2
   • Exclusion of drug-induced, alcoholic, and genetic liver diseases 2

2. Autoantibody Testing:

   • Conventional autoantibodies:

     • Antinuclear antibodies (ANA)
     • Smooth muscle antibodies (SMA)
     • Anti-liver/kidney microsome type 1 (anti-LKM1)
     • Anti-liver cytosol type 1 (anti-LC1) 2

   • Supplemental autoantibodies (when conventional tests are negative):

     • Anti-soluble liver antigen/liver pancreas (anti-SLA/LP)
     • Anti-actin
     • Perinuclear anti-neutrophil cytoplasmic antibodies (pANCA) 1

3. Histological Examination:

   • Interface hepatitis is the histological hallmark 2
   • Portal plasma cell infiltration is typical 2
   • Additional features: emperipolesis, hepatocellular rosette formation 1, 3
   • Centrilobular (zone 3) injury may represent early disease 2

Diagnostic Scoring Systems

Two validated scoring systems help establish the diagnosis:

1. Original Revised Scoring System (1999):

   • Pretreatment score ≥15: Definite AIH
   • Pretreatment score 10-15: Probable AIH 2

2. Simplified Scoring System (2008):

   • ≥7 points: Definite AIH
   • ≥6 points: Probable AIH 1

The simplified scoring system includes:

• ANA or SMA ≥1:40: +1 point
• ANA or SMA ≥1:80: +2 points
• or LKM ≥1:40: +2 points
• or SLA/LP positive (any titer): +2 points
• IgG >upper limit of normal: +1 point
• IgG >1.1× upper limit: +2 points
• Liver histology compatible with AIH: +1 point
• Liver histology typical of AIH: +2 points
• Absence of viral hepatitis: +2 points 2

AIH Classification

AIH is classified into two main types:

1. Type 1 AIH (80% of cases):

   • Positive for ANA and/or SMA
   • More common in adults
   • Often associated with other autoimmune diseases 1

2. Type 2 AIH:

   • Positive for anti-LKM1 and/or anti-LC1
   • More common in children
   • May have more severe presentation 1

Differential Diagnosis

The following conditions must be excluded:

• Viral hepatitis (hepatitis A, B, C)
• Wilson disease (check ceruloplasmin, copper levels)
• Alpha-1 antitrypsin deficiency (check phenotype)
• Drug-induced liver injury (detailed medication history)
• Alcoholic liver disease
• Non-alcoholic fatty liver disease
• Primary biliary cholangitis (check for AMA)
• Primary sclerosing cholangitis 2, 1

Special Considerations

• All children with AIH should undergo MR cholangiography to exclude autoimmune sclerosing cholangitis 1
• Patients with AIH and multiple endocrine disorders should be tested for APECED syndrome (check for AIRE gene mutations) 1
• Cirrhotic patients should undergo liver ultrasound every 6 months for HCC screening 1

Common Pitfalls and Caveats

1. Atypical presentations:

   • Acute or fulminant presentation may occur in up to 40% of cases 2
   • Asymptomatic patients can still have advanced disease 2
   • Normal IgG levels can be seen in 25-39% of acute presentations 2

2. Histological interpretation:

   • Absence of plasma cells does not exclude AIH diagnosis 2
   • Centrilobular injury pattern may represent early disease 2
   • Overlap features with other autoimmune liver diseases may be present 3

3. Autoantibody testing:

   • Testing should be performed according to guidelines to avoid false negatives 4
   • Titers may fluctuate during the course of disease 2
   • Negative conventional autoantibodies do not exclude AIH if other features are present 1

By following this diagnostic approach, clinicians can accurately diagnose AIH and initiate appropriate treatment to prevent disease progression and improve outcomes.