First-Line Treatment Options

The American Association for the Study of Liver Diseases recommends the first-line treatment for AIH-related chronic liver disease is prednisolone (or prednisone) plus azathioprine, which achieves remission in 80-90% of patients and significantly improves survival compared to no treatment 1, 2
The initial dose of prednisolone should be 30 mg/day, reducing to 10 mg/day over 4 weeks, plus azathioprine 1 mg/kg/day 2
Higher initial doses of prednisolone (up to 1 mg/kg/day) may result in more rapid normalization of liver enzymes 1
Azathioprine should be initiated when bilirubin levels are below 6 mg/dl, ideally two weeks after starting steroid treatment 1
The European Association for the Study of the Liver recommends initial azathioprine dosage should be 50 mg/day, increasing to a maintenance dose of 1-2 mg/kg based on response and toxicity 1

Treatment Goals and Monitoring

The treatment goal is complete normalization of liver enzymes and IgG levels 1
Persistent elevations of liver enzymes predict relapse after treatment withdrawal, ongoing activity on liver biopsy, progression to cirrhosis, and poor outcomes 1
Follow-up liver biopsy is not routinely required if there is complete biochemical normalization 3

The American Association for the Study of Liver Diseases recommends that failure of adequate response should prompt reconsideration of diagnosis or evaluation of treatment adherence 1, 4
In patients with confirmed diagnosis and adherence but sub-optimal response, increase dosage of prednisolone and azathioprine or consider alternative medications 1, 4
Second-line options include mycophenolate mofetil (MMF) and tacrolimus (TAC) 5, 6

The European Association for the Study of the Liver recommends treating acute severe AIH with high doses of intravenous corticosteroids (≥1 mg/kg) as early as possible 1
In patients with AIH-PBC variant syndrome, combined therapy with ursodeoxycholic acid (UDCA) and immunosuppressants is recommended 7, 8

Budesonide should not be used in cirrhotic patients due to risk of systemic side effects 1, 4
TPMT measurement should be considered to exclude homozygote TPMT deficiency, especially in patients with pre-existing leucopenia 2
Azathioprine hepatotoxicity is more common in patients with advanced liver disease 3

Persistent elevation of AST or ALT during treatment predicts 3-11 times higher risk of relapse, ongoing histological activity, progression to cirrhosis, and hepatocellular carcinoma in patients with autoimmune hepatitis, according to the American Association for the Study of Liver Diseases 9, 10
Liver biopsy before treatment termination is recommended, as 46% of patients with biochemical response for >6 months still have histological activity with Ishak score ≥4, which independently predicts death or liver transplantation, as suggested by the American Association for the Study of Liver Diseases 9, 10
Transient elastography should be performed after hepatic inflammation has been resolved in patients undergoing induction therapy to assess fibrosis, with a strength of evidence level of moderate, according to the American Association for the Study of Liver Diseases 9, 11

Tacrolimus may be more effective for refractory disease not responding to standard therapy, with a dosing regimen of 0.075 mg/kg daily, adjusted to maintenance of 1 mg daily to 3 mg twice daily, targeting trough level of 0.6-1.0 ng/mL, as recommended by the European Association for the Study of the Liver 12