What is the initial treatment for autoimmune liver disease?

Initial Treatment for Autoimmune Liver Disease

The initial treatment for autoimmune hepatitis should be prednisolone plus azathioprine, with prednisolone started at 30 mg/day (reducing to 10 mg/day over 4 weeks) plus azathioprine 1 mg/kg/day. 1

First-Line Treatment Approach

Corticosteroid Initiation

• Start with prednisolone 30 mg/day (or up to 1 mg/kg/day in severe cases)
• Reduce dose gradually over 4 weeks to 10 mg/day as transaminases normalize
• Higher initial doses (up to 1 mg/kg/day) may result in more rapid normalization of transaminases 1
• In acute severe AIH, use high-dose intravenous corticosteroids (≥1 mg/kg) immediately 1

Addition of Azathioprine

• Add azathioprine after 2 weeks of steroid treatment 1
• Initial dose: 50 mg/day
• Increase to maintenance dose of 1-2 mg/kg/day depending on response and toxicity 1
• Azathioprine can be initiated when bilirubin levels are below 6 mg/dl (100 μmol/L) 1

Treatment Monitoring and Goals

Laboratory Monitoring

• Monitor transaminases, bilirubin, and IgG levels every 3-6 months 1
• Complete normalization of transaminases and IgG levels should be the treatment goal 1
• Persistent elevations predict relapse after treatment withdrawal, ongoing activity on liver biopsy, progression to cirrhosis, and poor outcome 1

Treatment Duration

• Continue treatment for at least 2 years 1
• Maintain therapy for at least 12 months after normalization of transaminases 1
• Average duration of treatment until normalization is approximately 19 months 1

Special Considerations

TPMT Testing

• Consider thiopurine methyltransferase (TPMT) measurement before starting azathioprine
• Recommended in patients with pre-existing leucopenia to exclude homozygote TPMT deficiency 1

Budesonide Alternative

• In non-cirrhotic patients intolerant of prednisolone, budesonide (9 mg/day) plus azathioprine may be considered 1
• Do not use budesonide in cirrhotic patients or those with peri-hepatic shunting due to high risk of side effects 1
• Budesonide has a 90% first-pass hepatic clearance, making systemic side effects less common in patients with preserved liver function 1

Bone Health Protection

• Provide calcium and vitamin D supplementation to all patients on corticosteroids 1
• Perform DEXA scanning at 1-2 yearly intervals while on steroids 1
• Actively treat osteopenia and osteoporosis if detected 1

Management of Suboptimal Response

If inadequate response occurs despite confirmed diagnosis and adherence:

• Increase prednisolone dose (up to 60 mg daily) and azathioprine (up to 150 mg daily) 1
• Continue higher doses for at least 1 month, then reduce by 10 mg prednisolone and 50 mg azathioprine each month as improvement occurs 1
• Consider referral to a specialist center for alternative immunosuppressive options 1

Vaccination Recommendations

• Vaccinate against hepatitis A and hepatitis B early in susceptible patients 1

Common Pitfalls to Avoid

1. Delayed recognition of treatment failure: Patients who fail to improve within 7 days of high-dose steroids for acute severe AIH should be listed for emergency liver transplantation 1

2. Inadequate steroid dosing: Using too low initial doses may delay normalization of liver enzymes and histological improvement 2

3. Premature azathioprine introduction: Starting azathioprine simultaneously with steroids can make it difficult to distinguish azathioprine hepatotoxicity from primary non-response 1

4. Insufficient treatment duration: Stopping therapy too early leads to high relapse rates (50-86%) 3, 4

5. Neglecting bone health: Failure to provide calcium/vitamin D supplementation and monitor bone density can lead to significant osteoporosis 1