Diagnosis and Treatment of Autoimmune Hepatitis
The diagnosis of autoimmune hepatitis requires a comprehensive laboratory workup including autoantibody testing, elevated IgG levels, liver biopsy showing interface hepatitis with lymphoplasmacytic infiltrate, and exclusion of other liver diseases, while treatment should be initiated with a combination of prednisone and azathioprine for all patients with moderate to severe inflammation. 1
Diagnostic Criteria
Laboratory Testing
- Elevated aminotransferases (AST/ALT)
- Elevated serum IgG/hypergammaglobulinemia
- Positive autoantibodies:
- Type 1 AIH (80% of cases): ANA and/or SMA positive
- Type 2 AIH: Anti-LKM1 and/or anti-LC1 positive
- Significant titers in adults: ≥1:40 for ANA, SMA, anti-LKM1, and anti-LC1 1
- Significant titers in children: 1:20 for ANA/SMA and 1:10 for anti-LKM1 1
Histological Features
- Interface hepatitis (hallmark feature)
- Predominantly lymphoplasmacytic infiltrate
- Emperipolesis (lymphocytes within hepatocyte cytoplasm)
- Hepatocellular rosette formation 1, 2
- Centrilobular injury may represent early disease 2
Validated Scoring Systems
- 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 1
Exclusion of Other Liver Diseases
Essential to 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 Approach
Indications for Treatment
- All patients with moderate to severe inflammation should receive treatment, including:
- AST/ALT >5 times upper limit of normal
- Serum globulins >2 times upper limit of normal
- Liver biopsy showing confluent necrosis 1
- Treatment should also be considered in milder cases if:
- Patient has symptoms
- Cirrhosis is present on biopsy
- Patient is younger 1
First-Line Treatment
- Combination therapy with prednisone and azathioprine is preferred:
- Prednisone 30 mg/day (tapered over weeks to 10 mg/day or less)
- Azathioprine 50 mg/day 1
- This combination results in fewer corticosteroid-related side effects (10% versus 44%) compared to prednisone monotherapy 1
- Alternative first-line option: prednisone with mycophenolate mofetil 3
Treatment Duration and Monitoring
- Treatment should be given for at least 3-5 years
- Continue for at least 2 years after achieving complete biochemical response 3
- Regular monitoring of transaminases and IgG levels is essential 1
- Complete biochemical remission defined as normalization of both transaminases and IgG levels 1
- Consider repeat liver biopsy before withdrawing treatment 1
Special Considerations
Challenging Presentations
- 10-20% of patients may have insufficient response to standard therapy 1
- Diagnostic uncertainty may require a trial of steroids with quick tapering in atypical cases 1
- Differentiation from drug-induced liver injury can be challenging 4
Overlap Syndromes
- 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
- Manifestations of bile duct injury require careful evaluation for variant forms 5
Long-term Follow-up
- Lifelong monitoring in a designated liver clinic is recommended 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
- Corticosteroid-related side effects occur in up to 80% of patients after 2 years 1
Common Pitfalls and Caveats
- Diagnosis may be challenging in cholestatic and severe presentations 4
- Cirrhosis at presentation occurs in approximately 1/3 of adults and 1/2 of children 1
- Extra-hepatic autoimmune diseases are common in AIH patients and may require additional management 1
- Clinical manifestations vary widely, from asymptomatic to fulminant disease 3
- Autoantibody testing must be performed according to guidelines to be reliable 3