Treatment Plans for Autoimmune Hepatitis
First-Line Treatment Regimen
Start combination therapy with prednisone (or prednisolone) 30 mg/day plus azathioprine 1-2 mg/kg/day immediately in treatment-naïve patients without cirrhosis, acute severe hepatitis, or acute liver failure. 1, 2, 3
Standard Dosing Schedule
- Week 1: Prednisone 30 mg/day + Azathioprine 50 mg/day (US) or 1-2 mg/kg/day (Europe) 4, 2
- Week 2: Prednisone 20 mg/day + Azathioprine (same dose) 2
- Weeks 3-4: Prednisone 15 mg/day + Azathioprine (same dose) 2
- Maintenance: Taper prednisone to 10 mg/day + Azathioprine (same dose) by week 4 4, 2
This combination regimen produces significantly fewer corticosteroid-related side effects compared to prednisone monotherapy (10% versus 44%) 4, 2, making it the preferred approach for most patients.
Alternative First-Line Option for Non-Cirrhotic Patients
Budesonide 9 mg/day plus azathioprine may be used specifically in treatment-naïve, non-cirrhotic patients with early-stage disease who face high risk of steroid side effects. 1, 2 However, budesonide is contraindicated in cirrhotic patients due to impaired first-pass hepatic metabolism 3.
Pre-Treatment Considerations
TPMT Testing Before Azathioprine
Test for thiopurine methyltransferase (TPMT) activity before starting azathioprine to exclude homozygote TPMT deficiency, which predisposes to severe myelosuppression. 1, 2 If TPMT deficiency is confirmed or if severe pre-treatment cytopenia exists (leukocytes <4000/mm³, platelets <150,000/mm³), use prednisone monotherapy instead 2.
Hepatitis B Screening
Screen all patients for hepatitis B virus (HBV) by measuring HBsAg and anti-HBc before initiating immunosuppressive therapy. 5, 6 For patients with evidence of prior or current HBV infection, consult hepatology specialists regarding HBV antiviral prophylaxis before starting treatment 5, 6.
Treatment Duration and Goals
Continue treatment for at least 2 years and for at least 12 months after complete normalization of BOTH serum aminotransferases AND IgG levels. 4, 2 The average duration to achieve biochemical normalization is 18-24 months 4, 2.
Complete biochemical remission (normal ALT, AST, and IgG) should be the treatment goal, as persistent elevations predict relapse, ongoing histological activity, progression to cirrhosis, and poor outcomes 2.
Monitoring Strategy
Early Phase (First 6 Months)
- Check serum aminotransferases and IgG at 2-4 weeks to confirm early response 3
- Monitor monthly during dose adjustments 4, 3
- Assess treatment response by 4-8 weeks after initiation; serum aminotransferases typically improve within 2 weeks 4
Maintenance Phase
- Monitor serum aminotransferases and IgG every 3 months initially, then every 6 months once stable 3
- Consider elastography (FibroScan) to detect disease reactivation or progressive fibrosis 1, 3
- Monitor for drug toxicity: Complete blood count for azathioprine-induced myelosuppression, bone density (DEXA) at 1-2 year intervals for steroid-induced osteoporosis 4, 2, 3
Management of Inadequate Response
Non-Response (Deterioration Despite Compliance)
If patients deteriorate clinically despite compliant therapy, increase to high-dose therapy: prednisone 60 mg daily alone OR prednisone 30 mg daily plus azathioprine 150 mg daily for at least 1 month. 2, 3
Incomplete Response (Minimal Improvement After 2-3 Years)
For patients showing minimal or no improvement after 2-3 years of compliant therapy, reduce prednisone by 2.5 mg/month to the lowest level that prevents ALT elevation and continue indefinite azathioprine 2 mg/kg daily. 3
Second-Line Agents for Steroid-Refractory Cases
Consider mycophenolate mofetil (MMF) or tacrolimus as second-line treatment in patients who fail first-line therapy. 1, 4, 2 Recent evidence suggests MMF may have lower non-response rates (at 4 weeks) and higher complete biochemical response rates (at 12 months and end of follow-up) compared to azathioprine, with better safety profile 7.
Special Clinical Situations
Acute Severe Autoimmune Hepatitis
Immediately start high-dose intravenous prednisolone (≥1 mg/kg) as early as possible. 2, 3 If no improvement occurs within 7 days (some guidelines suggest 2 weeks), list for emergency liver transplantation 1, 2, 3.
Pregnancy
Azathioprine can be continued throughout pregnancy, whereas mycophenolate mofetil is contraindicated. 1 Prednisone is generally safe during pregnancy 1.
Cirrhotic Patients
Never use budesonide in cirrhotic patients due to impaired first-pass metabolism. 3 Use standard prednisone/prednisolone plus azathioprine combination instead 1, 3.
Long-Term Management After Remission
Relapse Risk
Relapse occurs in 50-90% of patients within 12 months of stopping treatment, even after achieving complete biochemical and histological remission. 4, 2, 3 Only 20-28% achieve sustained remission off therapy 2.
Maintenance Strategy After Relapse
After relapse, re-induce remission with combination therapy (prednisone + azathioprine), then maintain long-term with azathioprine 2 mg/kg daily alone. 4, 3 In one long-term study, 87% of adult patients remained in remission during a median observation interval of 67 months on azathioprine monotherapy 4, 8.
Consideration for Treatment Withdrawal
Liver tissue examination prior to drug withdrawal in individuals with ≥2 years of biochemical remission is preferred but not mandatory in adults and required in children. 1 This helps confirm histological remission and predict relapse risk.
Prevention of Treatment Complications
Bone Health
Provide calcium and vitamin D supplementation from treatment initiation. 4, 2, 3 Monitor bone mineral density with DEXA scanning at 1-2 year intervals in patients on corticosteroids 4, 2, 3.
Infection Prevention
Vaccinate against hepatitis A and B early in susceptible patients. 4, 2, 3 Avoid live vaccines during immunosuppressive therapy 5.
Monitoring for Serious Complications
- Perform periodic eye examinations for cataracts and glaucoma 3, 5
- Monitor for infections: Serious bacterial, fungal, and viral infections (including HBV reactivation, varicella, measles) can occur during immunosuppression 5, 6
- Watch for myelosuppression: Check complete blood counts regularly, especially with azathioprine 2 mg/kg/day 4, 8
Severe complications (osteoporosis, vertebral compression, diabetes, cataracts, hypertension, psychosis) typically develop after 18 months of therapy at prednisone doses >10 mg daily 4, emphasizing the importance of minimizing cumulative steroid exposure through combination therapy and aggressive tapering once remission is achieved 3.