What are the treatment guidelines for autoimmune hepatitis?

Autoimmune Hepatitis Treatment Guidelines

First-Line Treatment: Combination Therapy is Standard

Start all patients with combination therapy of prednisolone plus azathioprine unless they are cytopenic, pregnant, or completely deficient in TPMT activity. 1, 2

Specific Dosing Protocol

• Begin with prednisolone 30-60 mg/day for week 1, then taper weekly to 10 mg/day over 4 weeks 1
• Delay azathioprine initiation by 2 weeks after starting steroids to avoid confusing azathioprine hepatotoxicity with primary non-response 1, 2
• Once azathioprine is introduced, dose at 1 mg/kg/day initially, increasing to 1-2 mg/kg/day for maintenance 1, 2
• This combination achieves remission in 80-90% of patients and significantly improves survival 1, 3

Why Combination Over Monotherapy

• Combination therapy is strongly preferred because it reduces corticosteroid-related complications, particularly in elderly patients 1, 4
• Prednisone monotherapy should only be used in patients who are cytopenic, pregnant, or have complete TPMT deficiency 1

Treatment Goals: Complete Normalization Required

The therapeutic endpoint is complete normalization of both ALT and IgG levels—not just improvement, but complete normalization. 1, 2

• Persistent elevation of liver enzymes predicts relapse after treatment withdrawal, ongoing histological activity, progression to cirrhosis, and poor outcomes 1, 2
• Liver biopsy remains the best method to evaluate completeness of response 4, 5

Maintenance Therapy Duration

• Continue treatment with azathioprine 1 mg/kg/day and prednisolone 5-10 mg/day for at least 2 years and for at least 12 months after normalization of transaminases 1
• Once aminotransferases normalize, reduce prednisolone to 7.5 mg/day, then after 3 months taper to 5 mg/day 1, 2
• For patients requiring continuous therapy beyond 24 months (age ≥60 years) or 36 months (age ≤40 years) without achieving remission, long-term maintenance therapy adjusted to laboratory evidence of disease activity is justified 1

Critical Warning About Treatment Duration

• Continuous therapy for more than 3 years without achieving complete resolution is associated with progression to cirrhosis (54%) and need for transplantation (15%) 1

Alternative First-Line: Budesonide (Non-Cirrhotic Patients Only)

• In non-cirrhotic patients with severe steroid-related side effects, use budesonide 9 mg/day (3 mg three times daily) plus azathioprine 1-2 mg/kg/day 1, 2
• Budesonide achieves normalization of aminotransferases more frequently with fewer side effects compared to standard prednisone at 6 months 2
• Never use budesonide in cirrhotic patients due to risk of systemic side effects from impaired first-pass hepatic metabolism 1

Second-Line Therapy: Mycophenolate Mofetil

For patients who fail to achieve remission after 2 years on standard therapy or develop drug intolerance, mycophenolate mofetil (MMF) is the preferred second-line agent. 1, 2

• Start MMF at 1 g daily, increasing to maintenance of 1.5-2 g daily 2
• MMF is effective in 58% of patients with azathioprine intolerance versus only 23% with refractory disease 1, 2
• MMF is absolutely contraindicated in pregnancy due to severe cranial, facial, and cardiac abnormalities 1, 2

Other Salvage Options

• High-dose corticosteroids with or without high-dose azathioprine, 6-mercaptopurine, tacrolimus, or cyclosporin can be considered for refractory cases 3, 6, 5

Special Clinical Situations

Acute Severe Autoimmune Hepatitis

• Treat with high-dose intravenous corticosteroids (≥1 mg/kg) as early as possible 1, 2
• Consider liver transplant evaluation for fulminant cases 2

AIH-PBC Overlap Syndrome

• Use combined therapy with ursodeoxycholic acid (UDCA) 13-15 mg/kg/day plus immunosuppressants (corticosteroids and azathioprine) 1, 2
• Direct treatment at the predominant disease component 1, 2

Pregnancy Considerations

• Azathioprine requires risk-benefit analysis in pregnancy but may be continued if disease control requires it 1, 2
• MMF is absolutely contraindicated in pregnancy (Category D) 1, 2

Critical Pitfalls and Safety Monitoring

Before Starting Azathioprine

• Check TPMT levels before initiating azathioprine to exclude homozygote deficiency, especially in patients with pre-existing leucopenia 1, 2
• Discontinue immediately if intolerance symptoms emerge 2

Bone Health Protection

• Provide calcium and vitamin D supplementation to all patients on steroids 1
• Perform DEXA scanning at 1-2 yearly intervals while on steroids 1
• Actively treat osteopenia/osteoporosis 1

Vaccination

• Vaccinate against hepatitis A and hepatitis B early in susceptible patients 1

Monitoring for Non-Adherence

• Non-adherence is a major cause of relapse, particularly in adolescents and young adults 1, 2
• Regular monitoring of immunosuppressant drug levels is indicated 1, 2

Treatment Failure Evaluation

• Failure of adequate response should prompt reconsideration of the diagnosis or evaluation of treatment adherence before escalating therapy 1

Relapse Management

• Relapse after drug withdrawal occurs in 50-86% of patients 4, 3
• Re-treat with the original regimen, then maintain long-term with azathioprine 2 mg/kg daily 3, 5

Liver Transplantation Indications

• Consider transplantation for hepatic failure unresponsive to corticosteroid treatment, decompensated cirrhosis with MELD score ≥15, or hepatocellular carcinoma meeting transplantation criteria 3
• Autoimmune hepatitis recurs after transplantation in at least 17% of patients and typically improves after adjustments in immunosuppressive regimen 3