What is the management algorithm for autoimmune hepatitis?

Management Algorithm for Autoimmune Hepatitis

The preferred management strategy for autoimmune hepatitis is a combination of prednisolone (or prednisone) and azathioprine as first-line therapy, with prednisolone typically started at 0.5-1 mg/kg/day and azathioprine at 1-2 mg/kg/day. 1

Initial Diagnosis and Treatment Decision

1. Patient Selection for Treatment:

   • Treat patients with:
     • Incapacitating symptoms (fatigue, arthralgia)
     • Severe laboratory abnormalities
     • Bridging necrosis or multilobular necrosis on histology 1, 2
   • Consider observation only for asymptomatic patients with mild laboratory and histological changes 1

2. First-Line Treatment Options:

   a) Combination Therapy (Preferred):

   • Prednisolone 30-60 mg/day initially
   • Add azathioprine 50 mg/day after 2 weeks, increasing to 1-2 mg/kg/day maintenance 1

   Tapering Schedule (for 60kg patient):

   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

   b) Prednisolone Monotherapy:

   • For patients with contraindications to azathioprine
   • Initial dose: 60 mg daily
   • Taper gradually based on response

   c) Alternative First-Line Option:

   • Budesonide (9 mg/day) with azathioprine for non-cirrhotic patients 3
   • Contraindicated in cirrhotic patients due to portal-systemic shunting 1

Monitoring During Treatment

1. Laboratory Monitoring:

   • Weekly liver tests and blood counts for first 4 weeks
   • Then monthly once stable 1
   • Monitor serum AST/ALT and IgG levels as key indicators of response 2

2. Treatment Goals:

   • Complete biochemical remission (normalization of serum aminotransferases and IgG)
   • Histological resolution of inflammation 1

3. Additional Monitoring:

   • Baseline DEXA scan and repeat every 1-2 years while on prednisolone 2
   • Screen for glaucoma and cataracts after 12 months of prednisolone 2
   • Monitor for metabolic syndrome components (hypertension, hypertriglyceridemia, hyperglycemia) 1

4. Preventive Measures:

   • Calcium (1000-1200 mg/day) and vitamin D (400-800 IU/day) supplementation 1
   • Hepatitis A and B vaccination for susceptible patients 2, 1

Management of Treatment Response

1. Complete Response:

   • Continue treatment until normalization of laboratory tests
   • Consider liver biopsy before termination of immunosuppression 1
   • Note: Interface hepatitis is found in 55% of patients with normal serum AST and γ-globulin levels during therapy 1

2. Relapse Management (occurs in ~80% of patients):

   • Reinstitute therapy with prednisone and azathioprine until resolution
   • Then eliminate prednisone while increasing azathioprine to 2 mg/kg daily
   • Continue azathioprine indefinitely as maintenance therapy 2
   • Alternative: Low-dose prednisone (<10 mg daily, median 7.5 mg) to maintain AST <3x ULN 2

3. Treatment Failure:

   • Try high-dose prednisone (60 mg daily) or prednisone (30 mg daily) with azathioprine (150 mg daily) before considering alternatives 2

Second-Line Therapies

1. For Azathioprine Intolerance:

   • Mycophenolate mofetil (starting at 1g daily, increasing to 1.5-2g daily) 2, 1
   • Note: Mycophenolate has teratogenic risk in pregnancy 2

2. For Non-responders:

   • Tacrolimus (more effective than MMF for non-responders) 1, 4
   • Cyclosporine as salvage therapy 1, 4
   • Other options: 6-mercaptopurine, cyclophosphamide, methotrexate 2, 4

Special Situations

1. Treatment-Dependent Patients:

   • For patients not achieving remission after 24-36 months:
     • Consider long-term maintenance therapy with azathioprine 2 mg/kg daily 2
     • Young adults (<40 years) may need longer treatment (up to 36 months) 2

2. Pregnancy:

   • Risk of postpartum exacerbation
   • Consider discontinuing azathioprine if possible (FDA pregnancy category D)
   • Resume standard therapy 2 weeks before anticipated delivery 1

3. Liver Transplantation Indications:

   • Decompensated disease not responding to medical management
   • Fulminant hepatic failure
   • High MELD or Child-Pugh scores
   • Patients with acute liver failure should be listed even while receiving corticosteroids 1

Pitfalls and Caveats

1. Azathioprine-related:

   • Check TPMT activity before starting azathioprine to exclude homozygous TPMT deficiency
   • Monitor for myelosuppression, especially in patients with pre-existing cytopenia 2
   • Long-term azathioprine may be associated with malignancy risk in 8% of patients 2

2. Corticosteroid-related:

   • Higher risk of side effects in elderly patients
   • Withdrawal arthralgia occurs in 63% of patients on azathioprine maintenance 2

3. Treatment Decisions:

   • Histological assessment is critical - normal transaminases don't guarantee histological remission
   • Relapse is common (50-86%) after drug withdrawal 5
   • Better efficacy may be achieved using combination therapy from the beginning rather than sequential introduction 6