Diagnostic Criteria and Treatment Options for Autoimmune Hepatitis
The diagnosis of autoimmune hepatitis (AIH) requires a comprehensive laboratory workup, autoantibody testing, and liver biopsy, with treatment consisting of prednisone and azathioprine for all patients with moderate to severe inflammation. 1
Diagnostic Criteria
Clinical and Laboratory Features
- Female sex is a positive diagnostic factor (+2 points in diagnostic scoring) 2
- Laboratory abnormalities:
- Elevated transaminases (AST/ALT)
- Elevated serum globulins or IgG (>1.1× upper limit of normal)
- ALP:AST (or ALT) ratio <1.5 favors AIH diagnosis 2
Autoantibody Testing
AIH is classified into two main types based on autoantibody profiles 1:
- Type 1 AIH (80% of cases):
- Positive ANA and/or SMA
- Type 2 AIH:
- Positive anti-LKM1 and/or anti-LC1
Significant titers in adults are ≥1:40 by immunofluorescence, while in children, titers of 1:20 for ANA/SMA and 1:10 for anti-LKM1 are significant 1
Liver Biopsy
Liver biopsy is essential for diagnosis and should be obtained pre-treatment if possible 2. Key histological features include:
- Interface hepatitis (+3 points in scoring) 2
- Predominantly lymphoplasmacytic infiltrate (+1 point) 2, 3
- Rosetting of liver cells (+1 point) 2, 4
- Emperipolesis (lymphocytes within hepatocyte cytoplasm) 4, 5
- Centrilobular necrosis (present in 29% of AIH cases) 2
Diagnostic Scoring Systems
Two validated scoring systems help establish the diagnosis 1:
Original Revised Scoring System (1999):
- Definite AIH: ≥15 points
- Probable AIH: 10-15 points
Simplified Scoring System (2008):
- Definite AIH: ≥7 points
- Probable AIH: ≥6 points
Differential Diagnosis
Exclusion of other liver diseases is crucial 1:
- 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
Treatment Options
Indications for Treatment
Treatment should be initiated for 2, 1:
Moderate to severe inflammation (one or more of):
- AST/ALT >5× upper limit of normal
- Serum globulins >2× upper limit of normal
- Liver biopsy showing confluent necrosis
Consider treatment even in milder cases if:
- Patient has symptoms
- Cirrhosis is present on biopsy
- Patient is younger (to prevent cirrhosis development)
Standard Treatment Regimen
First-line therapy 1:
- Combination therapy with prednisone and azathioprine:
- Prednisone 30 mg/day (tapered over weeks to 10 mg/day or less)
- Azathioprine 50 mg/day
- This combination has fewer corticosteroid-related side effects (10% versus 44% with prednisone alone)
Monitoring and Follow-up
- Regular assessment of transaminases and IgG levels 1
- Complete biochemical remission defined as normalization of both transaminases and IgG levels
- Bone mineral densitometry at baseline and annually for patients on long-term corticosteroids
- HCC screening with liver ultrasound every 6 months in cirrhotic patients
- Consider repeat liver biopsy before withdrawing treatment to ensure histological remission
Special Considerations
- 10-20% of patients may have insufficient response to standard therapy 1
- AIH may overlap with primary biliary cholangitis or primary sclerosing cholangitis, requiring modified treatment approaches
- All children with AIH should undergo MR cholangiography to exclude autoimmune sclerosing cholangitis 1
Clinical Pitfalls and Caveats
Atypical presentations may occur, particularly in acute severe (fulminant) AIH, where autoantibodies may be absent, IgG levels normal, and diagnostic scores lower than in classical presentations 2
Centrilobular necrosis can be mistaken for toxic, ischemic, hypoxic, or drug-induced liver injury 2
Diagnostic uncertainty may require a short (≤2 weeks) treatment trial with corticosteroids, which can have both diagnostic and prognostic implications 2
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 and may require additional management 1