What is the treatment algorithm for autoimmune hepatitis?

Treatment Algorithm for Autoimmune Hepatitis

The first-line treatment for autoimmune hepatitis is a combination of prednisolone (or prednisone) and azathioprine, with prednisolone typically started at 0.5-1 mg/kg/day and azathioprine at 1-2 mg/kg/day. 1

Patient Selection for Treatment

• Absolute indications for treatment:
  • Incapacitating symptoms
  • Severe laboratory abnormalities
  • Bridging necrosis or multilobular necrosis on histology
  • Untreated severe disease has 60% mortality at 6 months 1

First-Line Treatment Protocol

Standard Combination Regimen

• Initial prednisolone dose: 30-60 mg/day
• Initial azathioprine dose: 50 mg/day, increasing to 1-2 mg/kg/day maintenance
• Monitoring: Weekly liver tests and blood counts for first 4 weeks, then monthly once stable 1

Recommended Tapering Schedule (for 60kg patient)

Week	Prednisolone (mg/day)	Azathioprine (mg/day)
1	60	-
2	50	-
3	40	50
4	30	50
5	25	100
6	20	100
7-8	15	100
9-10	12.5	100
>10	10	100

Alternative Approach

• Low-dose prednisone (<10 mg daily, median 7.5 mg) to maintain AST <3x ULN 1

Treatment Response Monitoring

• Key indicators: Serum AST/ALT and IgG levels 1
• Treatment goal: Complete biochemical remission (normalization of both serum aminotransferase and IgG levels) 1
• Liver biopsy: Best method to evaluate completeness of response 2

Management of Treatment Failure

For patients not responding to standard therapy:

1. First step: Try high-dose prednisone (60 mg daily) or prednisone (30 mg daily) with azathioprine (150 mg daily) 1

2. Second-line options for azathioprine intolerance:

   • Mycophenolate mofetil (starting at 1g daily, increasing to 1.5-2g daily) 1
   • Note: MMF has teratogenic risk in pregnancy

3. Other second-line agents:

   • Tacrolimus (more effective than MMF for non-responders: 56% vs 34% remission rate) 1
   • Cyclosporine (as salvage therapy) 1
   • 6-mercaptopurine, cyclophosphamide, methotrexate 1

Long-term Management

• Treatment duration: Consider long-term maintenance therapy with azathioprine 2 mg/kg daily if not achieving remission after 24-36 months 1
• Young adults (<40 years): May need longer treatment (up to 36 months) 1
• Relapse rate: 50-79% after drug withdrawal 3
• Relapse management: Long-term azathioprine (2 mg/kg daily) 1, 4

Prevention of Complications

• Bone health:

  • Baseline DEXA scan and repeat every 1-2 years while on prednisolone 1
  • All patients on steroids should receive calcium (1,000-1,200 mg) and vitamin D (400-800 IU) supplementation daily 1

• Ophthalmologic monitoring:

  • Screen for glaucoma and cataracts after 12 months of prednisolone 1
  • Corticosteroids may produce posterior subcapsular cataracts, glaucoma with possible damage to optic nerves 5

• Infection risk:

  • Monitor for increased risk of infection with any pathogen (viral, bacterial, fungal) 5, 6
  • Screen for hepatitis B before initiating immunosuppressive treatment 5, 6
  • Consider vaccination against hepatitis A and B for susceptible patients 1

• Metabolic monitoring:

  • Assess metabolic syndrome components (hypertension, hypertriglyceridemia, low HDL, hyperglycemia, central obesity) before starting glucocorticoid therapy 1

Special Populations

Pregnant Patients

• Risk for postpartum exacerbation
• Standard therapy should be resumed 2 weeks prior to anticipated delivery
• Azathioprine should be discontinued if possible during pregnancy (FDA pregnancy category D) 1
• Monitor serum liver enzymes at 3-week intervals for at least 3 months after delivery 1

Patients with Liver Disease

• Patients with moderate to severe liver disease should be monitored for increased signs of hypercorticism 6
• Reduced liver function affects glucocorticosteroid elimination 6

Liver Transplantation

• Indications for transplantation referral:

  • Decompensation at presentation
  • Severe disease with no/slow response to treatment
  • Fulminant hepatic failure
  • Clinical liver decompensation
  • High MELD or Child-Pugh scores 1

• Patients with acute liver failure due to autoimmune hepatitis should be placed on the transplant list even while receiving corticosteroids 1

Caution and Pitfalls

• Long-term azathioprine may be associated with malignancy risk in 8% of patients 1
• Avoid azathioprine in patients with severe pre-treatment cytopenia 1
• Carefully evaluate patients with severe pre-existing comorbidities (vertebral compression, psychosis, brittle diabetes, uncontrolled hypertension) before starting treatment 1
• When transferring from higher to lower systemic glucocorticosteroid effects, monitor for symptoms of acute adrenal suppression 6