What is the management approach for autoimmune hepatitis with elevated liver transferases?

Management of Autoimmune Hepatitis with Elevated Liver Transferases

The cornerstone of management for autoimmune hepatitis with elevated liver transferases is prompt initiation of corticosteroid therapy (prednisolone 0.5-1 mg/kg/day), followed by addition of azathioprine (1-2 mg/kg/day) as a steroid-sparing agent after 2 weeks when bilirubin levels decrease. 1

Diagnosis Confirmation

Before initiating treatment, confirm the diagnosis with:

• Laboratory tests:

  • Elevated aminotransferases (AST, ALT)
  • Increased IgG/gamma-globulin levels (though normal in ~10% of European patients and 25-39% of Japanese patients with acute presentation) 2
  • Autoantibodies: ANA, SMA (type 1 AIH) or anti-LKM1, anti-LC1 (type 2 AIH) 2

• Liver biopsy: Essential for diagnosis and assessment of disease severity 2

  • Interface hepatitis with lymphoplasmacytic infiltration
  • Plasma cell clusters
  • Hepatocyte rosettes

• Exclusion of other etiologies: Viral hepatitis, alcoholic liver disease, NAFLD, drug-induced liver injury, Wilson's disease, hemochromatosis 2

Treatment Protocol

Initial Treatment

1. Corticosteroids:

   • Prednisolone 0.5-1 mg/kg/day (typically 30-60 mg/day) 2, 1
   • For severe acute presentation: IV methylprednisolone ≥1 mg/kg 2

2. Add azathioprine after 2 weeks (when bilirubin decreases below 6 mg/dL):

   • Start at 50 mg/day
   • Increase to maintenance dose of 1-2 mg/kg/day 2, 1

Tapering Schedule (for 60kg patient) 2:

Week	Prednisolone (mg/day)	Azathioprine (mg/day)
1	60	-
2	50	-
3	40	50
4	30	50
5	25	100
6	20	100
7-8	15	100
9-10	12.5	100
>10	10	100

• Reduce prednisolone to 7.5 mg/day when aminotransferases normalize
• Further reduce to 5 mg/day after three months
• Consider tapering off steroids at 3-4 month intervals depending on response 2

Monitoring Response

• Weekly monitoring of liver tests and blood counts for first 4 weeks

• Monthly monitoring once stable 1

• Treatment targets:

  • Normalization of aminotransferases (AST/ALT)
  • Normalization of IgG levels 1, 3
  • Resolution of symptoms

• Important caveat: Normal serum parameters do not guarantee complete histological remission. About half of patients with normal serum parameters may still show residual histological activity (HAI 4-5) 3

Treatment Duration and Relapse Management

• Minimum treatment duration: 24 months 1
• Consider follow-up liver biopsy after 2 years to confirm histological remission 1
• Relapse rate: 50-86% after drug withdrawal 1
• For relapse: Reinstitute induction therapy followed by maintenance therapy, or consider long-term azathioprine monotherapy (2 mg/kg/day) for multiple relapses 1

Second-Line Therapy for Suboptimal Response

If inadequate response despite confirmed diagnosis and adherence:

1. Increase immunosuppression:

   • Increase prednisolone to 1-2 mg/kg/day methylprednisolone equivalent 2
   • Optimize azathioprine dosage

2. Alternative agents if still inadequate:

   • Mycophenolate mofetil (MMF): First choice second-line agent due to better side effect profile 1
   • Tacrolimus: Alternative second-line agent (56% vs 34% remission rate compared to MMF) 1
   • Calcineurin inhibitors (cyclosporine) 2

Special Considerations

• Acute severe AIH: Treat with high-dose IV corticosteroids (≥1 mg/kg) as early as possible 2
• Cirrhotic patients: Avoid budesonide due to risk of side effects from reduced first-pass metabolism 2
• Pregnancy: Azathioprine should be avoided; consider alternative agents 1
• Bone health: Provide calcium and vitamin D supplementation to all patients on steroids; consider DEXA scanning at 1-2 year intervals 1
• Surveillance: Hepatic ultrasonography every 6 months in cirrhotic patients, with serum alpha-fetoprotein level monitoring 2

Liver Transplantation Indications

Consider referral for transplantation in patients with:

• Decompensation at presentation
• Severe disease with no/slow response to treatment
• Fulminant hepatic failure
• High MELD or Child-Pugh scores 1

Remember that autoimmune hepatitis can recur after liver transplantation in 8-12% of patients at 1 year and 36-68% at 5 years 4, requiring vigilant monitoring.