What is the treatment for Autoimmune Hepatitis (AIH) related Chronic Liver Disease (CLD)?

Treatment of Autoimmune Hepatitis (AIH) Related Chronic Liver Disease

The first-line treatment for AIH-related chronic liver disease is prednisolone (or prednisone) plus azathioprine, which achieves remission in 80-90% of patients and significantly improves survival compared to no treatment. 1

First-Line Treatment Options

Standard Regimen

• Prednisolone/prednisone initially at 30 mg/day (reducing to 10 mg/day over 4 weeks) plus azathioprine 1 mg/kg/day 1
• Higher initial doses of prednisolone (up to 1 mg/kg/day) may result in more rapid normalization of transaminases 1
• Azathioprine should be initiated when bilirubin levels are below 6 mg/dl (100 μmol/L), ideally two weeks after starting steroid treatment 1
• Initial azathioprine dosage should be 50 mg/day, increasing to a maintenance dose of 1-2 mg/kg based on response and toxicity 1

Alternative First-Line Approach

• In non-cirrhotic patients intolerant of prednisolone, budesonide (9 mg/day) plus azathioprine may be considered 1
• Budesonide should NOT be used in cirrhotic patients or those with peri-hepatic shunting due to high risk of side effects from reduced first-pass metabolism 1
• In patients intolerant of azathioprine, prednisolone alone (in higher doses) is effective but has more side effects 1

Treatment Goals and Monitoring

• Complete normalization of transaminases and IgG levels should be the aim of treatment 1
• Persistent elevations of transaminases predict relapse after treatment withdrawal, ongoing activity on liver biopsy, progression to cirrhosis, and poor outcomes 1
• Follow-up liver biopsy is not routinely required if there is complete biochemical normalization 1
• Consider follow-up biopsy in patients with sub-optimal response to immunosuppression or treatment side effects 1

Management of Treatment Failure or Intolerance

• Failure of adequate response should prompt reconsideration of diagnosis or evaluation of treatment adherence 1
• In patients with confirmed diagnosis and adherence but sub-optimal response, increase dosage of prednisolone and azathioprine or consider alternative medications 1
• For patients who fail standard therapy (treatment failure, incomplete response, or drug intolerance), second-line options include: 1
  • Mycophenolate mofetil (MMF) - particularly effective for azathioprine-intolerant patients 1
  • Tacrolimus (TAC) - may be more effective than MMF for non-responders to standard therapy 1
  • Cyclosporine - limited data available 1

Special Situations

Acute Severe AIH

• Treat with high doses of intravenous corticosteroids (≥1 mg/kg) as early as possible 1
• If no improvement within seven days, list for emergency liver transplantation 1

Variant Syndromes

AIH-PBC Variant Syndrome

• Combined therapy with ursodeoxycholic acid (UDCA) and immunosuppressants is recommended 1

AIH-PSC Variant Syndrome

• Addition of UDCA to immunosuppressant therapy can be considered 1
• In patients with dominant AIH features, an alternative approach is to start with immunosuppressants only and then add UDCA if response is insufficient 1

Post-Liver Transplantation AIH

• Recurrent and "de novo" AIH occurs in about 20-25% of cases after liver transplantation 1
• Treatment should follow the standard management principles of AIH 1
• Usually managed by increasing the dose of corticosteroids or re-instituting their use with or without azathioprine or mycophenolate mofetil 1

Treatment Algorithm

1. Initial Assessment:

   • Evaluate disease severity (symptoms, liver function tests, histology)
   • Check for cirrhosis and comorbidities
   • Assess contraindications to standard therapy

2. First-Line Treatment:

   • Non-cirrhotic patients: Prednisolone + azathioprine OR budesonide + azathioprine
   • Cirrhotic patients: Prednisolone + azathioprine (avoid budesonide)
   • Acute severe AIH: High-dose IV corticosteroids

3. Response Evaluation (after 3-6 months):

   • Complete response: Taper prednisolone gradually
   • Partial response: Increase doses or consider second-line therapy
   • Non-response: Switch to second-line therapy

4. Second-Line Options:

   • Azathioprine intolerance: MMF + prednisolone
   • Treatment failure: TAC or MMF

Common Pitfalls and Caveats

• Do not use budesonide in cirrhotic patients due to risk of systemic side effects 1
• Delaying introduction of azathioprine (by about two weeks) can help resolve diagnostic uncertainties and avoid confusion between azathioprine-induced hepatotoxicity and primary non-response 1
• TPMT measurement should be considered to exclude homozygote TPMT deficiency, especially in patients with pre-existing leucopenia 1
• Azathioprine hepatotoxicity is more common in patients with advanced liver disease 1
• MMF is teratogenic and should be avoided in pregnancy 2
• Treatment withdrawal leads to relapse in many patients, making long-term maintenance therapy necessary in most cases 3