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

Diagnosis and Treatment of Autoimmune Hepatitis

The diagnosis of autoimmune hepatitis (AIH) requires a combination of laboratory tests, immunological markers, and liver biopsy, with liver biopsy being essential for definitive diagnosis as it cannot be diagnosed without compatible histological findings. 1

Diagnostic Criteria

Key Diagnostic Features

• Histological Features:

  • Portal plasma cell infiltration (key diagnostic feature) 1
  • Interface hepatitis 1
  • Predominantly lymphoplasmacytic infiltrate 1
  • Rosetting of liver cells 1
  • Emperipolesis (lymphocytes within hepatocyte cytoplasm) 1

• Laboratory Markers:

  • Elevated serum IgG (in 90% of cases, may be normal in acute presentations) 1
  • Elevated transaminases (AST/ALT) 1
  • ALP:AST (or ALT) ratio <1.5 1

• Autoantibodies (first-line testing by indirect immunofluorescence):

  • Antinuclear antibodies (ANA): present in 75-95% of AIH-1 1
  • Smooth muscle antibodies (SMA): present in up to 75% of AIH-1 1
  • Anti-liver kidney microsome type 1 (anti-LKM1): present in 70% of AIH-2 1
  • Anti-liver cytosol type 1 (anti-LC1): present in 30% of AIH-2 1

Validated Scoring Systems

1. Original Revised Scoring System (1999):

   • Definite AIH: ≥15 points
   • Probable AIH: 10-15 points 1

2. Simplified Scoring System (2008):

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

Scoring Components

• Female sex (+2 points)
• Personal or family history of other autoimmune diseases (+2 points)
• ALP:AST (or ALT) ratio <1.5 (+2 points)
• Elevated serum globulins or IgG (+1 to +3 points)
• Presence of autoantibodies such as ANA, SMA, or LKM-1 (+1 to +3 points)
• Interface hepatitis on histology (+3 points)
• Predominantly lymphoplasmacytic infiltrate (+1 point)
• Rosetting of liver cells (+1 point)
• Negative viral hepatitis markers (+3 points)
• No drug history (+1 point)
• Alcohol intake <25 g/day (+2 points) 1

Differential Diagnosis

Must exclude:

• Viral hepatitis
• Wilson disease
• Alpha-1 antitrypsin deficiency
• Drug-induced liver injury
• Alcoholic liver disease
• Non-alcoholic fatty liver disease
• Primary biliary cholangitis
• Primary sclerosing cholangitis 1

Treatment Options

First-Line Therapy

• Combination therapy with prednisone and azathioprine is the standard first-line treatment 1, 2
  • This combination has fewer corticosteroid-related side effects (10% versus 44% with prednisone alone) 1
  • Initial prednisone dose with gradual tapering to maintenance level 1

Indications for Treatment

Treatment should be initiated for:

• Moderate to severe inflammation (AST/ALT >5× upper limit of normal)
• Serum globulins >2× upper limit of normal
• Liver biopsy showing confluent necrosis 1

Treatment Duration and Monitoring

• Average treatment duration: 18-24 months 1
• Treatment endpoint: resolution of laboratory indices and tissue manifestations of active liver inflammation 1
• Liver biopsy prior to treatment termination is recommended 1
• Regular monitoring of transaminases and IgG levels is necessary 1
• Complete biochemical remission: normalization of both transaminases and IgG levels 1

Special Situations

• Diagnostic uncertainty: Short (≤2 weeks) treatment trial with corticosteroids 1
• Atypical presentations (e.g., acute severe/fulminant AIH): Modified treatment approaches 1
• Overlap syndromes (with primary biliary cholangitis or primary sclerosing cholangitis): Modified treatment approaches 1
• Treatment non-responders (10-20% of patients): Consider second-line agents 1, 2

Second-Line Therapies

For patients who don't respond to standard treatment or have unacceptable adverse effects:

• Budesonide
• Mycophenolate mofetil
• Cyclosporin
• Tacrolimus
• 6-mercaptopurine
• 6-thioguanine
• Rituximab
• Ursodeoxycholic acid
• Rapamycin
• Methotrexate 2

Long-term Management

• Lifelong monitoring in a designated liver clinic 1
• Bone mineral densitometry at baseline and annually for patients on long-term corticosteroids 1
• HCC screening with liver ultrasound every 6 months in cirrhotic patients 1
• All children with AIH should undergo MR cholangiography to exclude autoimmune sclerosing cholangitis 1

Common Pitfalls and Caveats

1. Diagnostic challenges:

   • Heterogeneous clinical presentation can delay diagnosis 3
   • Atypical histological features may be present, especially in acute presentations 4, 5
   • The current simplified histologic criteria may underscore AIH cases 5

2. Treatment pitfalls:

   • Incomplete treatment with dose titrations can lead to delayed or incomplete histological improvement 1
   • Premature treatment discontinuation can lead to relapse 1
   • Inadequate monitoring: 60% of patients who relapse do so despite disappearance of inflammatory features 1

3. Special considerations:

   • Cirrhosis at presentation occurs in approximately 1/3 of adult patients and 1/2 of children 1
   • Extra-hepatic autoimmune diseases are common in AIH patients 1
   • Long-term low-dose corticosteroid therapy or azathioprine may be necessary for patients who improve but don't achieve complete resolution after 36 months 1