What is the recommended treatment for autoimmune hepatitis type 2?

Treatment of Autoimmune Hepatitis Type 2

The recommended treatment for autoimmune hepatitis type 2 is combination therapy with prednisone (30 mg/day initially, tapering to 10 mg/day over 4 weeks) plus azathioprine (1-2 mg/kg/day), which should be continued for at least 2 years and for at least 12 months after normalization of liver enzymes. 1

Initial Treatment Regimen

The standard first-line approach uses combination therapy from the outset, as this strategy produces fewer corticosteroid-related side effects compared to prednisone monotherapy (10% versus 44%). 1

Specific dosing schedule:

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

Monitoring and Response Assessment

Assess treatment response at 4-8 weeks after initiation. 1 Serum aminotransferase levels should improve within 2 weeks of starting therapy. 2 If a positive biochemical response is observed, taper prednisone to 5-10 mg daily over the next 6 months while maintaining azathioprine. 1

Monitor serum aminotransferase levels monthly, as small decrements in prednisone dose can be associated with marked increases in aminotransferase levels. 3

Special Considerations for Type 2 AIH

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

Alternative therapy for pediatric type 2 AIH: Cyclosporin A has demonstrated efficacy in children with type 2 autoimmune hepatitis, particularly when risk factors for poor steroid tolerance exist or when conventional therapy fails. 4 In one pediatric series, alanine aminotransferase activity returned to normal within 6 months with minimal, well-tolerated side effects. 4

Treatment Duration and Endpoints

Continue treatment until remission is achieved, defined as normal laboratory indices and resolution of liver inflammation on biopsy. 1 The average duration of initial treatment is 18-24 months. 1

Complete normalization of transaminases and IgG levels should be the aim of treatment. 2 Biochemical remission achieved within 6 months is associated with lower frequency of progression to cirrhosis. 2

Management of Non-Response

For non-responding patients, consider higher doses of steroids combined with azathioprine 2 mg/kg/day. 1 Alternative options include tacrolimus or cyclosporine for steroid-refractory cases. 1

Treatment failure should be managed with high doses of prednisone alone (60 mg daily) or prednisone (30 mg daily) in conjunction with azathioprine (150 mg daily), continued for at least 1 month. 3

Long-Term Maintenance After Relapse

Relapse occurs in 50-90% of patients within 12 months of stopping treatment. 1 After relapse, consider long-term maintenance with azathioprine 2 mg/kg/day. 1

For patients who have relapsed more than once, treat with combination prednisone and azathioprine therapy, low-dose prednisone, or azathioprine only. 3 In the indefinite azathioprine strategy, increase azathioprine to 2 mg/kg daily and decrease prednisone by 2.5 mg each month until complete withdrawal. 3 Eighty-seven percent of adult patients remain in remission during a median observation interval of 67 months with this approach. 3, 5

Prevention of Treatment Complications

All patients should receive calcium and vitamin D supplementation, and bone mineral density should be monitored with DEXA scanning at 1-2 year intervals. 1 Vaccination against hepatitis A and B should be performed early in susceptible patients. 1

Common pitfall: Eighty percent of patients develop cosmetic changes (facial rounding, acne, dorsal hump, truncal obesity) after two years of corticosteroid therapy. 2 Severe complications (osteoporosis, vertebral compression, diabetes, cataracts, hypertension, psychosis) typically develop after 18 months of therapy at prednisone doses >10 mg daily. 2