What is the role of corticosteroids, such as prednisone, in the treatment of autoimmune hepatitis?

Role of Corticosteroids in Autoimmune Hepatitis

Corticosteroids, particularly prednisone or prednisolone, are the cornerstone of first-line therapy for autoimmune hepatitis (AIH), either alone or in combination with azathioprine, and should be initiated in all patients with active disease to prevent progression to cirrhosis and liver failure. 1

Indications for Treatment

• Treatment should be initiated in patients with serum aminotransferase levels >10-fold the upper limit of normal 1
• Patients with serum aminotransferase levels >5-fold the upper limit of normal with serum γ-globulin levels at least twice the upper limit of normal should be treated 1
• Histologic features of bridging necrosis or multiacinar necrosis compel therapy 1
• Most children should be treated at the time of diagnosis 1
• Patients with acute severe AIH should receive high-dose intravenous corticosteroids (≥1 mg/kg) as early as possible 1

Standard Treatment Regimens

Adults

• First-line regimen: Predniso(lo)ne as initial therapy followed by addition of azathioprine after two weeks 1
• Prednisone monotherapy: Starting with 60 mg/day, then tapering to 40 mg, 30 mg, and maintenance of 20 mg until endpoint 1
• Combination therapy (preferred): Prednisone starting at 30 mg/day with azathioprine 50 mg/day, then tapering prednisone to 20 mg, 15 mg, and maintenance of 10 mg with continued azathioprine 1
• The combination regimen is associated with fewer corticosteroid-related side effects (10% vs. 44%) 1

Children

• Prednisone 1-2 mg/kg daily (up to 60 mg/day) for two weeks either alone or with azathioprine 1-2 mg/kg daily 1
• Early use of azathioprine is recommended to minimize corticosteroid effects on growth 1

Alternative Corticosteroid Option: Budesonide

• Budesonide (9 mg/day) plus azathioprine may be considered in treatment-naive non-cirrhotic patients with early-stage disease 1
• Budesonide has 90% first-pass hepatic clearance, potentially reducing systemic side effects 1
• Biochemical remission is more likely with budesonide and azathioprine compared to prednisone and azathioprine (OR 2.19; 95% CI 1.30-3.67) 1
• Important caveat: Budesonide should NOT be used in patients with cirrhosis, portal hypertension, or acute severe AIH due to risk of reduced efficacy and increased side effects 1

Special Situations

Acute Severe AIH

• High-dose intravenous corticosteroids (≥1 mg/kg) should be administered as early as possible 1
• If no improvement within 7 days, patients should be evaluated for liver transplantation 1
• Prednisone or prednisolone alone (0.5-1 mg/kg daily in adults and up to 2 mg/kg in children) has been effective in 20-100% of patients with acute severe AIH 1

Treatment Duration and Monitoring

• Treatment should continue until resolution of symptoms, laboratory tests, and liver tissue abnormalities 2
• Complete normalization of transaminases and IgG levels should be the aim of treatment 1
• Serum aminotransferase levels should improve within 2 weeks of starting therapy 1
• Biochemical remission achieved within 6 months is associated with lower frequency of progression to cirrhosis 1

Corticosteroid-Related Side Effects

• 80% of patients develop cosmetic changes (facial rounding, acne, dorsal hump, truncal obesity) after two years of corticosteroid therapy 1
• Severe complications (osteoporosis, vertebral compression, diabetes, cataracts, hypertension, psychosis) typically develop after 18 months of therapy at prednisone doses >10 mg daily 1
• Most common reasons for treatment withdrawal: intolerable cosmetic changes/obesity (47%), osteopenia with vertebral compression (27%), and brittle diabetes (20%) 1
• Patients on long-term corticosteroid treatment should be monitored for bone disease with baseline and annual bone mineral densitometry 1

Management of Treatment Response

Relapse

• Relapse occurs in 50-79% of patients after drug withdrawal 3
• Should be retreated with the original regimen followed by long-term maintenance with azathioprine (2 mg/kg daily) 1, 3

Treatment Failure

• Warrants high doses of the original regimen 4
• Consider alternative immunosuppressants if no response 1

Clinical Pearls and Pitfalls

• The rapidity of response to treatment is the most important predictor of outcome 1
• Elderly patients (≥60 years) respond more quickly to treatment than young adults 1
• Laboratory features of cholestasis may indicate incomplete or delayed response or alternative diagnosis 1
• Non-response should prompt reconsideration of diagnosis and evaluation of treatment adherence 1
• Advanced cirrhosis can impair conversion of prednisone to prednisolone, but this is usually not sufficient to alter treatment response 1

By following these evidence-based guidelines for corticosteroid use in AIH, clinicians can effectively manage this condition and improve long-term outcomes for patients.