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

Autoimmune Hepatitis Diagnosis and Treatment

The diagnosis of autoimmune hepatitis (AIH) requires a combination of specific laboratory, immunological, and histological findings using validated scoring systems, with treatment indicated for all patients with moderate to severe disease, young patients, symptomatic patients, and those with cirrhosis even with mild activity. 1

Diagnostic Criteria

Two validated scoring systems are used to diagnose AIH:

Original Revised Scoring System (1999)

• Definite AIH: Score ≥15
• Probable AIH: Score 10-15 2, 1

Simplified Scoring System (2008)

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

Key Diagnostic Parameters

1. Demographics and Clinical Features:

   • Female sex (+2 points) 2
   • Personal or family history of other autoimmune diseases (+2 points) 2

2. Laboratory Parameters:

   • ALP:AST (or ALT) ratio <1.5 (+2 points) 2
   • Elevated serum globulins or IgG:

     • 2.0× upper limit: +3 points

     • 1.5-2.0× upper limit: +2 points
     • 1.0-1.5× upper limit: +1 point 2, 1

3. Autoantibodies:

   • ANA, SMA, or LKM-1:

     • 1:80: +3 points

     • 1:80: +2 points
     • 1:40: +1 point 2
   • Significant titers in adults: ≥1:40 for ANA, SMA, anti-LKM1, and anti-LC1 1
   • In children: titers of 1:20 for ANA/SMA and 1:10 for anti-LKM1 are significant 1

4. Histological Features:

   • Interface hepatitis (+3 points) 2, 3
   • Predominantly lymphoplasmacytic infiltrate (+1 point) 2, 4
   • Rosetting of liver cells (+1 point) 2, 5
   • Centrilobular necrosis (present in 29% of cases) 1, 4
   • Emperipolesis (lymphocytes within hepatocyte cytoplasm) 4, 5

5. Exclusion Criteria:

   • Negative viral hepatitis markers (+3 points) 2
   • No drug history (+1 point) 2
   • Alcohol intake <25 g/day (+2 points) 2
   • Absence of antimitochondrial antibodies (AMA) 2

Diagnostic Algorithm

1. Initial Evaluation:

   • Liver function tests (AST, ALT, ALP, bilirubin)
   • Serum immunoglobulins (particularly IgG)
   • Autoantibody testing (ANA, SMA, LKM-1, SLA)

2. Exclude Other Causes:

   • Viral hepatitis (HBV, HCV)
   • 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

3. Liver Biopsy:

   • Essential for diagnosis and prognosis assessment 3, 5
   • Look for interface hepatitis, plasma cell-rich infiltrate, rosettes, and emperipolesis 4
   • Centrilobular injury may represent early disease 5

4. Apply Scoring Systems:

   • Calculate score using either Original Revised or Simplified criteria
   • Interpret as definite, probable, or unlikely AIH 2, 1

Treatment Indications

Treatment should be initiated for:

1. Moderate to severe AIH:

   • AST/ALT >5× upper limit of normal
   • Serum globulins >2× upper limit of normal
   • Liver biopsy showing confluent necrosis 1

2. Special Populations:

   • Young patients
   • Symptomatic patients
   • Patients with cirrhosis (even with mild histological activity) 2, 1

3. Mild Disease Considerations:

   • Benefits of treating mild disease (Ishak necroinflammatory score <6) in asymptomatic older patients are not established
   • Treatment is not indicated if there is no biochemical or histological evidence of disease activity 2

Treatment Approach

First-line therapy is combination therapy with prednisone and azathioprine, which has fewer corticosteroid-related side effects (10% versus 44% with prednisone alone) 1, 6

Monitoring and Follow-up

1. Response Assessment:

   • Regular monitoring of transaminases and IgG levels
   • Complete biochemical remission defined as normalization of both transaminases and IgG 1

2. Long-term Monitoring:

   • Lifelong monitoring in a designated liver clinic
   • Bone mineral densitometry at baseline and annually for patients on long-term corticosteroids
   • HCC screening with liver ultrasound every 6 months in cirrhotic patients 1
   • Consider repeat liver biopsy before withdrawing treatment 1

Special Considerations

• About 10-20% of patients may have insufficient response to standard therapy 1
• Cirrhosis at presentation occurs in approximately 1/3 of adult patients and 1/2 of children 1
• Extra-hepatic autoimmune diseases are common and may require additional management 1
• AIH may overlap with primary biliary cholangitis or primary sclerosing cholangitis 1
• All children with AIH should undergo MR cholangiography to exclude autoimmune sclerosing cholangitis 1

Common Pitfalls and Caveats

1. Diagnostic Challenges:

   • Heterogeneous clinical, serological, and pathological features make diagnosis difficult 4
   • No single pathognomonic feature exists; diagnosis requires comprehensive evaluation 4
   • Atypical presentations may require a short (≤2 weeks) treatment trial with corticosteroids 1

2. Histological Interpretation:

   • Centrilobular injury pattern may be misdiagnosed as drug-induced liver injury 5
   • Plasma cell predominance may be subtle in some cases 4
   • Concurrent liver diseases may mask typical features 5

3. Treatment Considerations:

   • Spontaneous recovery may occur in some patients, making treatment decisions complex 2
   • Drug-related AIH may resolve on drug withdrawal, though this is poorly documented 2
   • Up to 40% of patients relapse despite initial response to treatment 6