What is the management and treatment of autoimmune hepatitis?

Management and Treatment of 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

Indications for Treatment

Absolute Indications

• Serum AST/ALT levels >10-fold ULN
• Serum AST/ALT levels >5-fold ULN with serum γ-globulin levels >2-fold ULN
• Histological features showing bridging necrosis or multilobular necrosis
• Incapacitating symptoms (fatigue, arthralgia) regardless of other disease severity indices 2

Uncertain Indications

• Asymptomatic patients with mild laboratory and histological changes
  • Decision must be balanced against possible risks of therapy
  • Consider referral to a hepatologist before starting therapy 2

Contraindications for Treatment

• Minimal or no disease activity or inactive cirrhosis
• Serious pre-existing comorbidities (vertebral compression, psychosis, brittle diabetes, uncontrolled hypertension)
• For azathioprine: severe pre-treatment cytopenia (WBC <2.5×10⁹/L or platelets <50×10⁹/L) 2

First-Line Treatment Regimens

Standard Regimen

1. Prednisolone + Azathioprine:
   • Initial prednisolone dose: 30-60 mg/day
   • Azathioprine: Start at 50 mg/day, increase to 1-2 mg/kg/day maintenance
   • Tapering schedule (for 60kg patient):
     • Week 1: Prednisolone 60 mg/day
     • Week 2: Prednisolone 50 mg/day
     • Week 3: Prednisolone 40 mg/day, add azathioprine 50 mg/day
     • Week 4: Prednisolone 30 mg/day, azathioprine 50 mg/day
     • Week 5: Prednisolone 25 mg/day, azathioprine 100 mg/day
     • Week 6: Prednisolone 20 mg/day, azathioprine 100 mg/day
     • Weeks 7-8: Prednisolone 15 mg/day, azathioprine 100 mg/day
     • Weeks 9-10: Prednisolone 12.5 mg/day, azathioprine 100 mg/day

     • Week 10: Prednisolone 10 mg/day, azathioprine 100 mg/day 1

Alternative First-Line Regimen

1. Budesonide + Azathioprine (for non-cirrhotic patients without acute severe disease):
   • Budesonide: 9 mg/day
   • Azathioprine: 1-2 mg/kg/day 1
   • Important: Budesonide is contraindicated in cirrhotic patients or those with portosystemic shunts due to portal-systemic shunting 1

Monitoring and Follow-up

• Weekly liver tests and blood counts for first 4 weeks, then monthly once stable 1
• Assess TPMT activity in patients with pre-existing cytopenia or those who develop cytopenia during therapy 1
• Calcium and vitamin D supplementation (1,000-1,200 mg and 400-800 IU daily, respectively) for all patients on steroids 2, 1
• DEXA scanning at 1-2 year intervals 1
• Vaccination against hepatitis A and B for susceptible patients 2, 1

Treatment Goals

• Complete biochemical remission (normalization of serum aminotransferases and IgG levels) 1
• Histological resolution of inflammation
• Liver biopsy recommended before termination of immunosuppressive treatment 1

Management of Treatment Failure or Incomplete Response

Second-Line Therapies

1. Mycophenolate mofetil (MMF):

   • Preferred initial second-line agent, especially for azathioprine intolerance 1

2. Tacrolimus:

   • Alternative second-line agent
   • More effective than MMF for non-responders (56% vs 34% remission rate) 1

3. Cyclosporine:

   • May be considered as salvage therapy 1

Special Populations

Pregnant Patients

• Risk for postpartum exacerbation
• Standard therapy should be resumed 2 weeks prior to anticipated delivery
• Consider discontinuing azathioprine 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

HBV-Infected Patients

• HBsAg-negative/anti-HBc-positive patients should undergo periodic serological testing (HBsAg, HBV DNA) during conventional therapy to detect HBV reactivation 2
• Patients with serological evidence of previous HBV infection who are treated with high-dose glucocorticoids or other immune modulators are at moderate risk for HBV reactivation and should be considered for preemptive antiviral therapy 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
• High MELD or Child-Pugh scores 1

Patients with acute liver failure due to AIH should be placed on the transplant list even while receiving corticosteroids 1.

Common Pitfalls and Caveats

1. Failure to recognize diverse presentations: AIH may present acutely, have mild inflammatory activity, lack autoantibodies, or exhibit atypical histological changes 3

2. Underestimating the importance of early treatment: Untreated patients with severe disease have high mortality (60% at 6 months) 2

3. Premature treatment withdrawal: Rapid withdrawal of immunosuppression often leads to disease relapse 4

4. Overlooking bone health: Assess bone density at baseline in patients with risk factors for osteoporosis and every 2-3 years in adult patients 2

5. Neglecting metabolic syndrome risk: Assess for metabolic syndrome components (hypertension, hypertriglyceridemia, low HDL, hyperglycemia, central obesity) before starting glucocorticoid therapy 2