Workup and Treatment for Autoimmune Hepatitis
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
Diagnostic Workup
Initial Laboratory Tests
- Complete liver panel (AST, ALT, ALP, bilirubin, albumin)
- Gamma-globulin or IgG levels (>1.5 times upper limit of normal is characteristic) 1
- Complete blood count
- Prothrombin time/INR
- Exclusion tests for other liver diseases:
- Viral hepatitis serologies (HAV, HBV, HCV)
- Ceruloplasmin (Wilson disease)
- Alpha-1 antitrypsin levels and phenotype
- Iron studies and ferritin
- Drug history assessment
Autoantibody Testing
- Antinuclear antibodies (ANA)
- Smooth muscle antibodies (SMA)
- Anti-liver kidney microsome type 1 (anti-LKM1)
- Anti-liver cytosol type 1 (anti-LC1)
Significant titers in adults: ≥1:40 by immunofluorescence 1 Significant titers in children: ≥1:20 for ANA/SMA and ≥1:10 for anti-LKM1 1
Liver Biopsy
- Essential for definitive diagnosis unless contraindicated 2, 1
- Key histological features:
- Interface hepatitis
- Predominantly lymphoplasmacytic infiltrate
- Rosetting of liver cells
- Absence of biliary changes or other features suggesting alternative diagnoses
Diagnostic Scoring Systems
Two validated scoring systems can help establish the diagnosis:
| Scoring System | Definite AIH | Probable AIH |
|---|---|---|
| Original Revised (1999) | ≥15 | 10-15 |
| Simplified (2008) | ≥7 | ≥6 |
Treatment
Indications for Treatment
- All patients with moderate to severe inflammation should receive treatment, including those with: 2
- AST/ALT >5 times upper limit of normal
- Serum globulins >2 times upper limit of normal
- Liver biopsy showing confluent necrosis
- Treatment should also be considered in milder cases if: 2
- Patient has symptoms
- Cirrhosis is present on biopsy
- Patient is younger
First-Line Treatment Regimens
Adult Regimens: 2
Combination therapy (preferred):
- Prednisone 30 mg/day (tapered over weeks to 10 mg/day or less)
- Azathioprine 50 mg/day
Prednisone monotherapy:
- Starting at 40-60 mg/day
- Tapered to maintenance dose of 20 mg/day or less
Children Regimens: 2
- Prednisone 1-2 mg/kg/day (up to 60 mg/day) for two weeks
- With or without azathioprine 1-2 mg/kg/day
- Taper prednisone over 6-8 weeks to 0.1-0.2 mg/kg/day or 5 mg daily
The combination regimen of prednisone and azathioprine is associated with fewer corticosteroid-related side effects (10% versus 44%) and is generally preferred. 2
Monitoring and Maintenance
Treatment Response Monitoring
- Regular assessment of transaminases and IgG levels 1
- Complete biochemical remission is defined as normalization of both transaminases and IgG levels 1
- Consider repeat liver biopsy before withdrawing treatment to ensure histological remission
Long-term Monitoring
- Lifelong monitoring in a designated liver clinic 2
- Bone mineral densitometry at baseline and annually for patients on long-term corticosteroids 2
- HCC screening with liver ultrasound every 6 months in cirrhotic patients 2
- All children with AIH should undergo MR cholangiography to exclude autoimmune sclerosing cholangitis 2, 1
Treatment Challenges and Pitfalls
- Side effects of therapy: Corticosteroid-related side effects (cosmetic changes, osteopenia, diabetes, hypertension) occur in up to 80% of patients after 2 years 2
- Incomplete response: About 10-20% of patients may have insufficient response to standard therapy
- Diagnostic uncertainty: Consider a trial of steroids with quick tapering in atypical cases; recurrence after tapering supports the diagnosis 3
- Overlap syndromes: AIH may overlap with primary biliary cholangitis or primary sclerosing cholangitis, requiring modified treatment approaches
Special Considerations
- Acute severe presentation: May require more aggressive initial immunosuppression
- Pregnancy: Azathioprine is generally avoided; prednisone monotherapy is preferred
- Cirrhosis at presentation: Occurs in approximately 1/3 of adult patients and 1/2 of children 2
- Extra-hepatic autoimmune diseases: Common in AIH patients and may require additional management 2