What is the typical management of autoimmune hepatitis?

Management of Autoimmune Hepatitis

Initial Treatment Regimen

Start with combination therapy of prednisone (30 mg/day initially, tapering to 10 mg/day over 4 weeks) plus azathioprine (1-2 mg/kg/day) as first-line treatment for all patients with autoimmune hepatitis. 1, 2, 3

This combination regimen produces significantly fewer corticosteroid-related side effects compared to prednisone monotherapy (10% versus 44%) while maintaining equivalent efficacy. 2, 3

Specific Dosing Schedule

• Week 1: Prednisone 30 mg/day + Azathioprine 50 mg/day (US) or 1-2 mg/kg/day (Europe) 2, 3
• Week 2: Prednisone 20 mg/day + Azathioprine (same dose) 2
• Weeks 3-4: Prednisone 15 mg/day + Azathioprine (same dose) 2
• Maintenance: Prednisone 10 mg/day + Azathioprine (same dose) until treatment endpoint 2, 3

Alternative Approach for Severe Hyperbilirubinemia

For patients with bilirubin >6 mg/dL, start prednisone first, then add azathioprine after 2 weeks as a safer approach. 2, 3

Alternative Regimen for Non-Cirrhotic Patients

Budesonide 9 mg/day plus azathioprine may be used specifically in treatment-naive, non-cirrhotic patients with early-stage disease who face high risk of steroid side effects (psychosis, poorly controlled diabetes, severe osteoporosis). 2, 3

Pre-Treatment Considerations

TPMT Testing

Measure thiopurine methyltransferase (TPMT) activity before starting azathioprine to exclude homozygote TPMT deficiency, particularly in patients with pre-existing leucopenia (white blood cell counts <2.5 × 10⁹/L or platelet counts <50 × 10⁹/L). 1, 2

Common pitfall: While TPMT testing is recommended, full TPMT deficiency is rare, and TPMT activity is not consistently predictive of azathioprine toxicity in all patients. 1

Contraindications to Azathioprine

Use prednisone monotherapy in patients with:

• Severe pre-treatment cytopenia 2
• Complete TPMT deficiency 1
• Pregnancy (discontinue azathioprine and use prednisone alone) 1, 4

Monitoring and Response Assessment

Early Monitoring

Assess treatment response at 4-8 weeks after initiation. 2, 3 Serum aminotransferase levels should improve within 2 weeks of starting therapy. 4

Monitor serum aminotransferase levels monthly, as small decrements in prednisone dose can be associated with marked increases in aminotransferase levels. 4

Expected Timeline

• 80-90% of patients achieve biochemical improvement with transaminases normalizing within 6 months in most responders 3
• Normal liver tests are achieved in 66-91% of treated patients within 2 years, with average duration to normalization being 19 months 2

Treatment Goals and Duration

Treatment Endpoint

Complete normalization of BOTH serum aminotransferases AND IgG levels must be the treatment goal. 2, 3 Persistent elevations predict relapse, ongoing histological activity, progression to cirrhosis, and poor outcomes. 2

Common pitfall: Do not accept biochemical endpoint of <2 times the upper limit of normal as adequate—relapse after termination of therapy in those patients is universal. 1

Duration of Treatment

Continue treatment for at least 2 years and for at least 12 months after normalization of liver enzymes. 2, 4, 3 The average duration of initial treatment is 18-24 months. 1, 4

Pre-Withdrawal Liver Biopsy

Perform liver biopsy before termination of treatment to ensure full resolution of disease. 1 Interface hepatitis is found in 55% of patients with normal serum AST and γ-globulin levels during therapy, and these individuals typically relapse after cessation of treatment. 1

Key point: A normal repeat liver biopsy and absence of portal tract plasma cells are associated with a lower risk of relapse. 1

Management of Incomplete Response

Definition

Incomplete response occurs when protracted therapy has improved clinical, laboratory, and histological indices but not induced complete resolution after 36 months of treatment. 1

Management Strategy

For confirmed non-responders, increase to high-dose therapy: 2, 3

• Prednisone 60 mg daily alone, OR
• Prednisone 30 mg daily plus azathioprine 150 mg daily (up to 2 mg/kg/day)
• Continue for at least 1 month 2

Alternatively, consider tacrolimus or cyclosporine for steroid-refractory cases. 1, 2, 3

Important: If no improvement occurs, contact a liver transplant center or seek expert advice. 1

Management of Acute Severe Autoimmune Hepatitis

Treat immediately with high-dose intravenous corticosteroids (≥1 mg/kg) as early as possible. 2, 3

If no improvement occurs within 7 days, list for emergency liver transplantation. 2

For patients with liver failure, bridging necrosis on biopsy, or jaundiced patients whose MELD score does not rapidly improve on treatment, contact a liver transplant center immediately. 1

Relapse Management

Relapse Frequency

Relapse occurs in 50-90% of patients within 12 months of stopping treatment, even after achieving complete biochemical and histological remission. 2, 4, 3 Only 20-28% achieve sustained remission off therapy. 2

Treatment of Relapse

After relapse, reinitiate combination prednisone and azathioprine therapy using the same induction regimen. 4

For patients who have relapsed more than once, consider long-term maintenance with azathioprine 2 mg/kg/day. 2, 4, 3 With this approach, 87% of adult patients remain in remission during median follow-up of 67 months. 4, 3

Prevention of Treatment Complications

Mandatory Prophylaxis

All patients must receive from treatment initiation: 2, 4, 3

• Calcium and vitamin D supplementation
• DEXA scanning for bone mineral density monitoring at 1-2 year intervals
• Vaccination against hepatitis A and B early in susceptible patients

Steroid-Related Complications

Severe complications (osteoporosis, vertebral compression, diabetes, cataracts, hypertension, psychosis) typically develop after 18 months of therapy at prednisone doses >10 mg daily. 4

Key strategy: Minimize cumulative steroid exposure by using combination therapy rather than prednisone monotherapy. 2

Long-Term Maintenance for Treatment-Dependent Patients

For patients requiring continuous therapy beyond 36 months without achieving complete resolution, institute long-term maintenance therapy with the lowest achievable histological and biochemical activity using minimal side effects. 1

Options include:

• Long-term low-dose prednisone (gradually decrease to 10 mg daily) 1
• Long-term azathioprine 2 mg/kg daily 1

Important consideration: Progression to cirrhosis occurs in 54% and need for liver transplantation in 15% of patients requiring continuous therapy for >36 months without achieving resolution. 1