Autoimmune Hepatitis Workup and Treatment
Diagnostic Workup
The diagnosis of autoimmune hepatitis (AIH) requires a comprehensive laboratory workup, autoantibody testing, and liver biopsy, followed by immunosuppressive therapy with corticosteroids alone or in combination with azathioprine as first-line treatment. 1
Initial Laboratory Testing
- Complete liver function tests (AST, ALT, ALP, GGT, bilirubin)
- Serum immunoglobulins (particularly IgG levels)
- Hypergammaglobulinemia with IgG >1.5 times upper limit of normal is characteristic 1
- Complete blood count
- Coagulation profile
Autoantibody Testing
- Test by indirect immunofluorescence on freshly prepared rodent substrate (kidney, liver, stomach sections) 2
- Significant titers in adults: ≥1:40 for:
- Antinuclear antibodies (ANA)
- Smooth muscle antibodies (SMA)
- Anti-liver kidney microsome type 1 (anti-LKM1)
- Anti-liver cytosol type 1 (anti-LC1) 1
- In children, significant titers are lower: 1:20 for ANA/SMA and 1:10 for anti-LKM1 1
- Additional testing for anti-soluble liver antigen (SLA) antibodies (associated with more severe disease) 2
Exclusion of Other Liver Diseases
- Viral hepatitis serologies (HBV, HCV)
- Wilson disease (ceruloplasmin, 24-hour urinary copper)
- Alpha-1 antitrypsin deficiency
- Drug-induced liver injury history
- Alcohol use assessment
- Non-alcoholic fatty liver disease evaluation
- Primary biliary cholangitis (anti-mitochondrial antibody)
- Primary sclerosing cholangitis (MRCP/ERCP) 1
Liver Biopsy
- Essential for definitive diagnosis unless contraindicated 1
- Key histological finding: interface hepatitis 3
- Helps rule out other liver diseases and assess severity/stage
Diagnostic Scoring Systems
- Original Revised Scoring System (1999): Definite AIH ≥15, Probable AIH 10-15
- Simplified Scoring System (2008): Definite AIH ≥7, Probable AIH ≥6 1
Special Considerations
- All children with AIH should undergo MR cholangiography to exclude autoimmune sclerosing cholangitis 1
Treatment
Indications for Treatment
- All patients with moderate to severe inflammation:
- AST/ALT >5 times upper limit of normal
- Serum globulins >2 times upper limit of normal
- Liver biopsy showing confluent necrosis 1
- Consider treatment in milder cases if:
- Patient has symptoms
- Cirrhosis is present on biopsy
- Patient is younger 1
First-Line Treatment
- Standard therapy: Combination of corticosteroids and azathioprine (preferred due to lower corticosteroid-related side effects) 1, 4
- Initial: Prednisone 30-60 mg/day (or equivalent) with or without azathioprine 50-100 mg/day
- Taper prednisone gradually once response is achieved
- Maintain on lowest effective dose of immunosuppression
Treatment Response Monitoring
- Regular monitoring of transaminases and IgG levels 1
- Complete biochemical remission defined as normalization of both transaminases and IgG levels 1
- Consider repeat liver biopsy before withdrawing treatment to ensure histological remission 1
Second-Line Therapies for Non-responders
For patients who don't respond to standard treatment or have unacceptable side effects:
- Budesonide (steroid with high first-pass metabolism)
- Mycophenolate mofetil
- Calcineurin inhibitors (cyclosporine, tacrolimus)
- 6-mercaptopurine or 6-thioguanine
- Rituximab
- Ursodeoxycholic acid 5
Long-term Monitoring
- Regular follow-up in a designated liver clinic 1
- Monitor for treatment-related complications
- Cirrhotic patients should undergo liver ultrasound every 6 months for HCC screening 1
- Assess for relapse after treatment withdrawal
Important Considerations
- AIH is highly responsive to immunosuppressive therapy, which should be instituted promptly to prevent rapid deterioration 2
- If left untreated, AIH has a high mortality rate 3
- Standard therapy is efficacious in approximately 80% of patients 5
- Treatment should be individualized based on disease severity, comorbidities, and patient factors
- Long-term immunosuppression carries risks of opportunistic infections and malignancies 5