What is the treatment for autoimmune hepatitis?

Treatment for Autoimmune Hepatitis

The first-line treatment for autoimmune hepatitis is prednisolone (or prednisone) plus azathioprine, with prednisolone starting at 30 mg/day (reducing to 10 mg/day over 4 weeks) plus azathioprine 1 mg/kg/day. 1

Initial Treatment Approach

First-Line Therapy

• Combination therapy: Prednisolone plus azathioprine is the standard of care

  • Prednisolone: Start at 30 mg/day and reduce to 10 mg/day over 4 weeks
  • Azathioprine: 50 mg/day initially, with target maintenance dose of 1-2 mg/kg/day 2, 1
  • Azathioprine should ideally be initiated two weeks after steroid treatment when bilirubin levels are below 6 mg/dl (100 μmol/L) 1

• Monotherapy option: Prednisolone alone (starting with 60 mg/day and reduced to 20 mg over four weeks) can be used if azathioprine is contraindicated 2

  • However, this has higher side effect rates (44% vs 10% with combination therapy) 2

Treatment Goals

• Complete biochemical remission (normalization of both serum aminotransferase and IgG levels) 2
• Histological resolution of inflammation 2
• Average treatment duration: 18-24 months 2

Monitoring and Assessment

Follow-up Schedule

• Monthly liver tests initially, then every 3 months once stable 1
• Liver biopsy recommended before termination of immunosuppressive treatment 2
  • Interface hepatitis is found in 55% of patients with normal serum AST and γ-globulin levels during therapy 2

Treatment Endpoints

• Normalization of serum AST/ALT, γ-globulin, and IgG levels 2
• Resolution of histological inflammation 2
• Treatment should continue for at least 2 years with repeatedly normal liver function tests and immunoglobulin levels 2

Management of Suboptimal Response

Incomplete Response

• Defined as clinical and laboratory improvement without complete resolution after 36 months of treatment 2
• Options:
  1. Long-term low-dose corticosteroid therapy (gradual decrease to 10 mg daily) 2
  2. Long-term azathioprine (2 mg/kg daily) for corticosteroid-intolerant individuals 2

Treatment Failure or Drug Intolerance

• For patients who fail to achieve remission or cannot tolerate first-line agents:
  • Mycophenolate mofetil (MMF) is suggested as the initial second-line agent due to better side-effect profile 2
  • Tacrolimus (TAC) is an alternative second-line agent 2
    • TAC is superior to MMF for patients who are non-responders to standard therapy (56% vs 34% remission rate) 2
    • MMF and TAC are comparably effective for patients intolerant to standard therapy (92% vs 94% remission rate) 2

Special Considerations

Cirrhosis

• Treatment should always be initiated in patients with advanced fibrosis or cirrhosis as this represents a negative prognostic predictor 2
• Substantial regression of fibrosis is possible even in advanced cases with successful treatment 2

Liver Transplantation

• Consider referral for transplantation in patients with:
  • Decompensation at presentation
  • Severe disease with no or very slow response to treatment
  • Fulminant hepatic failure
  • Clinical liver decompensation (ascites, hepatic encephalopathy, hepatorenal syndrome)
  • MELD score >15 or Child-Pugh score >10 2

Relapse Management

• Relapse is common (50-86%) after drug withdrawal 1
• Options include:
  • Reinstitution of induction therapy followed by maintenance therapy
  • Long-term maintenance with azathioprine monotherapy (2 mg/kg/day) for patients with multiple relapses 1

Common Pitfalls and Caveats

1. Inadequate treatment endpoints: Accepting <2 times upper limit of normal for liver enzymes is insufficient; complete normalization of laboratory indices is required to reduce relapse risk 2

2. Premature discontinuation: Liver biopsy before stopping treatment is essential as interface hepatitis may persist despite normal laboratory values 2

3. Azathioprine monotherapy for induction: This strategy results in high mortality rates (36-41%) and should be avoided 2

4. Overlooking mild disease: Even patients with mild disease should be treated or closely monitored with regular follow-up including liver biopsy if ALT/IgG levels increase 2

5. Drug-specific considerations:

   • Check TPMT levels before starting azathioprine to exclude homozygote TPMT deficiency 1
   • Provide calcium and vitamin D supplementation to all patients on steroids 1
   • Avoid azathioprine in pregnancy 1

By following this treatment algorithm and being vigilant about monitoring response and managing complications, most patients with autoimmune hepatitis can achieve remission and prevent progression to cirrhosis and liver failure.