Does prednisone (corticosteroid) have a role in the treatment of hepatitis, specifically autoimmune hepatitis?

Prednisone is Essential First-Line Therapy for Autoimmune Hepatitis

Prednisone (or prednisolone) is the cornerstone treatment for autoimmune hepatitis and should be initiated immediately in patients with moderate-to-severe disease, combined with azathioprine to minimize steroid-related complications. 1, 2 This combination achieves biochemical remission in 80% of patients within 6 months and is superior to monotherapy in reducing corticosteroid side effects (10% versus 44%). 1, 3

When to Start Prednisone

Initiate treatment immediately if patients meet any of these criteria: 3

• Serum aminotransferases >10-fold the upper limit of normal
• Serum aminotransferases >5-fold the upper limit of normal with serum γ-globulin levels at least twice the upper limit of normal
• Moderate to severe disease with symptoms, regardless of age
• Any degree of cirrhosis with even mild histological activity

Do not treat asymptomatic older patients with mild AIH (Ishak necroinflammatory score <6) and no biochemical or histological evidence of active disease. 3

Standard Dosing Regimen

The preferred regimen is combination therapy with prednisone plus azathioprine: 1, 2

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

For patients with severe hyperbilirubinemia (>6 mg/dL), start prednisone first, then add azathioprine after 2 weeks as a safer approach. 2, 4

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, 4, 3 However, budesonide should NOT be used in patients with cirrhosis or acute severe AIH. 1

Treatment Duration and Goals

Continue treatment for at least 2 years and for at least 12 months after normalization of liver enzymes. 2, 4 The average duration to achieve normalization is 19 months. 2

Complete normalization of BOTH serum aminotransferases AND IgG levels must be the treatment goal, as persistent elevations predict relapse, ongoing histological activity, progression to cirrhosis, and poor outcomes. 2, 4, 3

Monitoring Response

Serum aminotransferases should improve within 2 weeks of starting therapy, and the rapidity of response is the most important predictor of outcome. 3 Assess response at 4-8 weeks after treatment initiation. 2 If positive biochemical response is observed, taper prednisone to 5-10 mg daily over the next 6 months while maintaining azathioprine. 2

Management of Non-Response

For confirmed non-responders after 3 years, increase to high-dose therapy: prednisone 60 mg daily alone OR prednisone 30 mg daily plus azathioprine 150 mg daily (or up to 2 mg/kg/day) for at least 1 month. 2, 4, 3

For steroid-refractory cases, use alternative second-line agents including tacrolimus, cyclosporine, or mycophenolate mofetil. 2 Tacrolimus was superior to MMF at achieving biochemical remission in patients who had not responded to standard therapy (56% versus 34%, P = 0.03). 1

Acute Severe Autoimmune Hepatitis

Treat acute severe AIH 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, 3

Prevention of Treatment Complications

All patients must receive calcium and vitamin D supplementation from treatment initiation. 2, 4 Monitor bone mineral density with DEXA scanning at 1-2 year intervals. 1, 2 Vaccinate against hepatitis A and B early in susceptible patients. 2, 4

Cosmetic changes occur in 80% of patients after 2 years of corticosteroid treatment regardless of regimen. 1 Severe complications (osteopenia with vertebral compression, brittle diabetes, psychosis, hypertension, malignancy) are uncommon but typically occur after protracted therapy (>18 months) with prednisone alone at 20 mg daily. 1

Long-Term Management and Relapse

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

After relapse, consider long-term maintenance with azathioprine 2 mg/kg/day, which maintains remission in 83-87% of adult patients during median follow-up of 67 months. 4, 3 This is particularly recommended for younger patients, LKM antibody-positive patients, and SLA-positive patients. 3

Special Populations

For children: Prednisone is the mainstay at 1-2 mg/kg daily (up to 60 mg/day) for two weeks, then taper over 6-8 weeks to 0.1-0.2 mg/kg daily or 5 mg daily with azathioprine. 1 Early use of azathioprine is recommended for all children without contraindications due to significant deleterious effects of long-term corticosteroids on linear growth, bone development, and physical appearance. 1

For patients with cytopenia: Consider measuring thiopurine methyltransferase (TPMT) activity before starting azathioprine to exclude homozygote TPMT deficiency. 2 Prednisone monotherapy is appropriate for patients with severe pre-treatment cytopenia. 1, 2

Critical Pitfall to Avoid

Do NOT use prednisone for hepatitis B-associated chronic active hepatitis, as it is not effective and may be deleterious. 5 Prednisone is specifically indicated for autoimmune hepatitis, which can be differentiated from other types by serological markers. 5