Is azathioprine used to treat autoimmune hepatitis?

Azathioprine in Autoimmune Hepatitis Treatment

Yes, azathioprine is a standard treatment for autoimmune hepatitis (AIH), typically used in combination with prednisone/prednisolone as the preferred first-line therapy to induce and maintain remission while reducing steroid-related side effects. 1

Standard Treatment Regimens

Combination Therapy (Preferred Approach)

• Prednisone/prednisolone plus azathioprine is the standard combination therapy for AIH, providing equivalent efficacy to prednisone alone but with significantly fewer steroid-related side effects (10% vs 44%) 1
• Typical dosing regimen for adults:
  • Prednisone: Starting at 30mg/day and gradually tapering to 10mg/day maintenance
  • Azathioprine: 50mg/day (USA) or 1-2mg/kg/day (Europe) 1

Delayed Azathioprine Introduction Strategy

• Starting with prednisone monotherapy (0.5-1mg/kg/day) and delaying azathioprine introduction by about two weeks 1
• This approach helps resolve diagnostic uncertainties and avoids confusion between azathioprine-induced hepatotoxicity and primary non-response 1
• Particularly useful in patients with advanced liver disease, as azathioprine hepatotoxicity risk increases in this population 1

Patient Selection for Azathioprine

Ideal Candidates for Combination Therapy

• Patients who will be treated continuously for at least 6 months 1
• Individuals at higher risk for steroid-related complications:
  • Postmenopausal women
  • Patients with emotional instability
  • Pre-existing osteoporosis
  • Brittle diabetes
  • Labile hypertension
  • Obesity
  • Young female patients concerned about weight gain and cosmetic side effects 1

Cautions and Contraindications

• Azathioprine should be avoided or used with caution in:
  • Patients with malignancy
  • Cytopenia (white blood cell counts <2.5×10^9/L or platelet counts <50×10^9/L)
  • Established thiopurine methyltransferase (TPMT) deficiency
  • Pregnancy (though risk-benefit assessment should be individualized) 1

Monitoring and Safety Considerations

TPMT Testing

• Thiopurine methyltransferase (TPMT) mediates elimination of 6-mercaptopurine, affecting therapeutic action and drug toxicities 2
• Approximately 0.3% of patients of European or African ancestry have little or no TPMT activity (homozygous deficient), and about 10% have intermediate activity (heterozygous deficient) 2
• Pretreatment testing for TPMT activity is recommended, especially in patients with pretreatment cytopenia 1

Side Effects and Complications

• Azathioprine side effects occur in <10% of patients receiving 50mg daily and can include:
  • Cholestatic hepatitis
  • Veno-occlusive disease
  • Pancreatitis
  • Nausea and vomiting
  • Rash
  • Bone marrow suppression 1
• Long-term complications include a theoretical risk of malignancy (5% with cumulative treatment of 42 months), with an incidence of 1 per 194 patient-years 1

Treatment Response and Long-term Management

• Complete biochemical and histological remission is the goal of therapy 1
• After achieving normal aminotransferases and IgG levels, prednisolone can be reduced to 7.5mg/day, then to 5mg/day after three months, with further tapering at 3-4 month intervals 1
• For maintenance therapy after relapse, options include:
  • Continuing low-dose prednisone (median 7.5mg daily)
  • Increasing azathioprine to 2mg/kg daily as a steroid-sparing strategy 1

Alternative Options for Azathioprine Intolerance

• Mycophenolate mofetil (MMF) is the second-line drug of choice for patients intolerant to azathioprine 1
• 6-Mercaptopurine (6-MP) may be effective in 75% of patients with azathioprine intolerance 3
• Other options for treatment failure include cyclosporine, tacrolimus, and budesonide 1, 4

Special Considerations

• In patients with features of both AIH and primary sclerosing cholangitis (PSC), combination therapy with UDCA and immunosuppression (prednisolone and azathioprine) is recommended 1
• All children diagnosed with AIH should be treated due to the typically more aggressive course of disease in pediatric patients 1

Remember that treatment should be response-guided and individualized based on disease severity, comorbidities, and patient-specific risk factors 1.