What is the treatment for a patient presenting with sudden jaundice, hyperbilirubinemia, elevated IgG (Immunoglobulin G) levels, and positive autoantibodies?

Treatment of Autoimmune Hepatitis Presenting with Acute Severe Disease

The correct answer is C: Prednisolone plus Azathioprine. This patient's presentation of sudden jaundice, hyperbilirubinemia, elevated IgG, and positive autoantibodies is diagnostic of acute severe autoimmune hepatitis (AIH), which requires immediate immunosuppressive therapy with corticosteroids combined with azathioprine as the standard of care. 1

Immediate Treatment Approach

Start high-dose corticosteroids immediately at ≥1 mg/kg/day (typically prednisolone 30-60 mg/day), preferably intravenously in severe presentations. 1, 2

• The European Association for the Study of the Liver emphasizes treating acute severe AIH as early as possible with high-dose intravenous corticosteroids. 2
• All patients with acute severe AIH should receive a trial of corticosteroids at sufficiently high doses (≥1 mg/kg), with available data suggesting this approach improves outcomes even in severe presentations. 1

Add azathioprine after initial stabilization, typically starting at 50 mg/day when bilirubin is below 6 mg/dL, ideally within 2 weeks of starting steroids. 3, 4, 2

• The combination of prednisolone plus azathioprine achieves remission in 80-90% of AIH patients while dramatically reducing corticosteroid-related side effects compared to prednisone monotherapy (10% versus 44% incidence). 1, 3, 5
• Increase azathioprine to maintenance dose of 1-2 mg/kg/day based on response. 3, 4

Why Other Options Are Incorrect

Plasma exchange (Option A) is NOT indicated for autoimmune hepatitis. 1

• There is no evidence supporting plasma exchange in AIH management.
• Immunosuppression with corticosteroids is the established treatment.

Phototherapy (Option B) is NOT appropriate for AIH-related hyperbilirubinemia. 1

• Phototherapy is only used for unconjugated hyperbilirubinemia in neonates (e.g., Crigler-Najjar syndrome). 1
• AIH causes conjugated hyperbilirubinemia from hepatocellular injury, which does not respond to phototherapy.

Antibiotics (Option D) are NOT the primary treatment, though prophylactic antimicrobials may be considered in severe liver failure. 1

• The EASL guidelines note that prophylactic antibiotics and antifungal agents may be justified in liver failure due to infection risk with corticosteroids, but this is adjunctive, not primary therapy. 1

Critical Monitoring and Decision Points

Assess response within 7 days of initiating treatment. 1, 2

• Failure to improve serum bilirubin, MELD-Na, or UKELD within 7 days has strong negative prognostic value. 1
• If no improvement occurs within 7 days, immediately list for emergency liver transplantation while continuing corticosteroids. 1, 2

Treatment goals include complete normalization of serum aminotransferases (AST, ALT) AND IgG levels. 1, 2

• Serum aminotransferases should improve within 2 weeks; most patients achieve biochemical remission within 6-12 months. 3, 2
• Persistent elevations predict relapse, ongoing histological activity, progression to cirrhosis, and poor outcomes. 4, 2

Dosing Schedule

Week 1: Prednisolone 30-60 mg/day (start high in severe disease) + Azathioprine 50 mg/day (if bilirubin <6 mg/dL). 3, 4, 2

Week 2-4: Taper prednisolone to 20 mg/day, then 15 mg/day, maintaining azathioprine. 3, 2

Maintenance: Prednisolone ≤10 mg/day + Azathioprine 1-2 mg/kg/day for at least 2 years and at least 12 months after normalization of liver enzymes. 3, 4, 2

Critical Pitfalls to Avoid

Do NOT delay corticosteroid initiation while awaiting liver biopsy or complete serological workup in acute severe presentations. 1, 2

• Clinical suspicion with jaundice, elevated IgG, and positive autoantibodies is sufficient to start treatment immediately. 6

Do NOT use budesonide in this patient, as it should only be used in treatment-naive, non-cirrhotic patients with early-stage disease. 2

• Budesonide is contraindicated in cirrhosis due to impaired first-pass metabolism causing systemic side effects. 3

Do NOT start azathioprine immediately if bilirubin is ≥6 mg/dL, as azathioprine hepatotoxicity is more common in advanced liver disease. 3, 2

• Begin with corticosteroids alone, then add azathioprine after bilirubin improves. 2

Consider measuring thiopurine methyltransferase (TPMT) before starting azathioprine if pre-existing cytopenia exists, to exclude homozygote deficiency. 3, 4, 2

Prognosis and Transplant Considerations

Overall mortality in acute severe AIH ranges from 19-45%, with liver transplantation required in 9-81% of cases depending on severity. 1

• In the largest UK study, 48% of corticosteroid-treated patients required transplantation versus 100% of untreated patients (p=0.01). 1
• Six deaths (19%) occurred, all post-transplant, emphasizing the importance of early medical therapy. 1

Liver transplantation should be considered early if no improvement occurs within 7 days, as the optimal timing for transplant in non-responders remains uncertain. 1, 2