When should treatment be initiated for autoimmune hepatitis?

When to Treat Autoimmune Hepatitis

Immunosuppressive treatment should be initiated in all patients with active autoimmune hepatitis (AIH), including those with serum AST/ALT levels >10-fold ULN, at least 5-fold ULN with serum γ-globulin levels ≥2-fold ULN, and/or histological features of bridging necrosis or multilobular necrosis. 1

Absolute Indications for Treatment

• Symptomatic patients with clinical manifestations such as fatigue and arthralgia 1
• Laboratory abnormalities:
  • Serum AST/ALT >10-fold ULN
  • Serum AST/ALT ≥5-fold ULN with serum γ-globulin/IgG ≥2-fold ULN 1
• Histological findings:
  • Bridging necrosis
  • Multilobular necrosis 1
• All children with confirmed AIH diagnosis 1

Treatment Considerations for Mild Disease

For patients with mild disease (minimal symptoms, mild laboratory and histological abnormalities), treatment decisions should follow this algorithm:

1. Assess disease activity:

   • ALT <3× ULN and Hepatitis Activity Index (HAI) <4/18 = mild disease 1
   • ALT >3× ULN or HAI ≥4/18 = active disease requiring treatment 1

2. For mild disease, consider:

   • Patient age (younger patients tolerate immunosuppression better) 1
   • Presence of advanced fibrosis/cirrhosis (treat if present) 1
   • Patient preference 1
   • Comorbidities that may worsen with immunosuppression 1

3. If deciding not to treat mild disease:

   • Monitor every 3 months with ALT and IgG measurements 1
   • Perform follow-up liver biopsy if ALT/IgG increase 1

Rationale for Treatment

Untreated severe AIH carries a high mortality rate (60% at 6 months), and histological findings of bridging necrosis or multilobular necrosis progress to cirrhosis in 82% of untreated patients with a 5-year mortality of 45% 1.

Even in mild disease, untreated asymptomatic patients have lower 10-year survival than treated counterparts (67% versus 98%, P < 0.01) 1. While spontaneous improvement occurs in some asymptomatic patients with mild disease (12%), it is less common and slower than in treated patients (63%) 1.

Contraindications to Treatment

Treatment should not be initiated in:

• Patients with minimal or no disease activity or inactive cirrhosis (but close monitoring every 3-6 months is required) 1
• Patients with serious pre-existing comorbidities unless the disease is severe and progressive 1
• For azathioprine specifically: patients with severe cytopenia (WBC <2.5×10^9/L or platelets <50×10^9/L) 1

Special Considerations

Acute Severe AIH or Acute Liver Failure

• Acute severe AIH: Trial of prednisone/prednisolone (0.5-1 mg/kg daily in adults, up to 2 mg/kg in children) 1
• AIH with acute liver failure: Evaluate directly for liver transplantation 1
• If no improvement in laboratory tests or clinical worsening within 1-2 weeks of glucocorticoid therapy, proceed to liver transplantation evaluation 1

Children

The disease process in children appears more severe than in adults, with >50% having cirrhosis at presentation 1. Therefore, all children with established AIH diagnosis should receive treatment 1.

Treatment Regimens

Once the decision to treat is made, standard regimens include:

• Prednisone alone (60 mg daily) OR
• Lower dose prednisone (30 mg daily) plus azathioprine (50 mg daily in US or 1-2 mg/kg daily in Europe) 1

The combination therapy has similar efficacy but fewer side effects (10% vs 44%) compared to prednisone monotherapy 1.

Remember that the goal of treatment is complete biochemical and histological resolution to prevent disease progression 1. Regular monitoring is essential, even after treatment cessation, due to the high relapse rate (50-90% within 12 months of stopping treatment) 2.