What is the treatment for autoimmune hepatitis?

Treatment of Autoimmune Hepatitis

Start combination therapy with prednisone 30 mg/day (tapering to 10 mg/day over 4 weeks) plus azathioprine 1-2 mg/kg/day (typically 50 mg/day) as first-line treatment, which achieves remission in 80-90% of patients and significantly improves survival. 1, 2, 3

First-Line Treatment Regimen

Standard Combination Therapy (Preferred)

• Initiate prednisone 30 mg/day plus azathioprine 50 mg/day (or 1-2 mg/kg/day) simultaneously. 1, 2, 3
• Taper prednisone to 10 mg/day over the first 4 weeks while maintaining azathioprine at the same dose. 1, 2
• This combination produces significantly fewer corticosteroid-related side effects compared to prednisone monotherapy (10% versus 44%). 1, 2

Important Timing Considerations

• Only start azathioprine when bilirubin is below 6 mg/dL, ideally two weeks after initiating steroids. 2, 3
• Measure thiopurine methyltransferase (TPMT) levels before azathioprine initiation to exclude homozygote deficiency, especially in patients with pre-existing leucopenia. 2

Alternative Monotherapy Option

• Prednisone alone starting at 60 mg daily, then tapered to 40 mg, 30 mg, and maintenance of 20 mg is appropriate for patients with cytopenia, pregnancy, TPMT deficiency, or malignancy. 2

Budesonide Consideration

• Budesonide 9 mg/day with azathioprine may be considered as first-line therapy, but should NOT be used in patients with cirrhosis or acute severe AIH due to risk of systemic side effects. 2

Treatment Monitoring

Early Response Assessment

• Serum aminotransferase levels should improve within 2 weeks of starting therapy. 1, 2, 3
• Assess treatment response formally at 4-8 weeks after initiation. 1, 3
• Monitor serum aminotransferase levels monthly, as small decrements in prednisone dose can trigger marked increases in aminotransferase levels. 1

Treatment Goals

• Aim for complete normalization of both transaminases (AST, ALT) AND IgG levels, not just improvement. 1, 2, 3
• Biochemical remission achieved within 6 months is associated with lower frequency of progression to cirrhosis. 1, 2
• Normalization of laboratory indices before treatment termination reduces the relative risk of relapse by 3-fold to 11-fold. 2

Treatment Duration and Withdrawal

Minimum Treatment Duration

• Continue treatment for at least 2 years AND for at least 12 months after normalization of liver enzymes. 1, 2
• Average duration of initial treatment is 18-24 months. 1

Pre-Withdrawal Assessment

• Perform liver biopsy before terminating treatment to ensure full histological resolution, as 55% of patients with normal serum enzymes may still have persistent interface hepatitis. 2, 3
• Failure to achieve complete normalization of liver enzymes and IgG leads to almost universal relapse after treatment withdrawal. 2

Management of Treatment Failure or Incomplete Response

Definition and Initial Approach

• Treatment failure is defined as persistent severe laboratory or histologic abnormalities despite standard therapy. 4
• For non-responding patients, escalate to higher doses of prednisone (60 mg daily) alone or prednisone (30 mg daily) with azathioprine (150 mg daily), continued for at least 1 month. 1

Second-Line Agents

For Azathioprine Intolerance:

• Mycophenolate mofetil (MMF) is the first second-line agent, starting at 1 g daily and increasing to maintenance of 1.5-2 g daily. 2

For Refractory Disease:

• Tacrolimus (starting dose 0.075 mg/kg daily) may be more effective for patients not responding to standard therapy. 2
• Cyclosporine (2-5 mg/kg daily) has shown effectiveness in inducing and maintaining remission, particularly in pediatric patients. 2

Management of Relapse

Relapse Rates and Re-Treatment

• Relapse occurs in 50-90% of patients within 12 months of stopping treatment. 1
• After relapse, re-treat with combination prednisone and azathioprine therapy. 1

Long-Term Maintenance After Multiple Relapses

• For patients who have relapsed more than once, consider long-term maintenance with azathioprine 2 mg/kg/day, which maintains remission in 87% of adult patients during a median observation of 67 months. 1
• Long-term low-dose prednisone (gradually decreased to 10 mg daily) is an alternative for corticosteroid-intolerant individuals. 2

Special Populations

Acute Severe Autoimmune Hepatitis

• Administer high-dose intravenous corticosteroids (≥1 mg/kg) as early as possible. 2, 3
• If no improvement within 7 days, evaluate immediately for liver transplantation. 2, 3

Pediatric Patients

• Treatment regimens are similar to adults but with dose adjustments. 2, 3
• Use azathioprine (1-2 mg/kg daily) or 6-mercaptopurine (1.5 mg/kg daily) early to minimize steroid effects on growth. 2, 3
• Response to treatment is excellent in children, with normalization of liver tests in 75-90% after 6-9 months. 2

Prevention of Treatment Complications

Bone Health

• All patients should receive calcium and vitamin D supplementation from treatment initiation. 1, 3
• Monitor bone mineral density with DEXA scanning at 1-2 year intervals. 1, 3
• Severe complications (osteoporosis, vertebral compression, diabetes, cataracts, hypertension, psychosis) typically develop after 18 months of therapy at prednisone doses >10 mg daily. 1, 2

Vaccination

• Perform vaccination against hepatitis A and B early in susceptible patients. 1, 3

Liver Transplantation Indications

Urgent referral for liver transplantation is indicated for:

• Decompensation at presentation or fulminant hepatic failure 3
• Clinical liver decompensation during treatment 3
• Hepatocellular carcinoma 3
• MELD score >15 or Child-Pugh score >10 3

Common Pitfalls to Avoid

• Do not withdraw treatment based solely on normalized transaminases—liver biopsy may still show active inflammation in 55% of cases. 2, 3
• Do not use budesonide in cirrhotic patients or acute severe AIH, as it carries risk of systemic side effects in these populations. 2
• Do not start azathioprine when bilirubin is above 6 mg/dL, as this increases risk of bone marrow toxicity. 2, 3
• Cosmetic side effects of corticosteroids occur in 80% of patients after 2 years of treatment, which may affect adherence. 2