Latest EASL Guidelines for Autoimmune Hepatitis (2015)
Diagnosis
The simplified scoring system (2008) from the International Autoimmune Hepatitis Group is the recommended tool for everyday clinical practice, while the revised scoring system (1999) helps diagnose difficult cases by incorporating treatment response. 1
Key Diagnostic Considerations
Perform (MR) cholangiography in adult AIH patients with cholestatic laboratory changes to identify sclerosing cholangitis. 1
Test for PBC and PSC in all patients showing cholestatic features, as overlap syndromes can occur both at diagnosis and during follow-up. 1
The heterogeneity of AIH is substantial—it affects patients from infancy to octogenarians, can present as mild subclinical disease or fulminant hepatic failure, and may overlap with PBC, PSC, DILI, NASH, or viral hepatitis. 1
Treatment Indications
All patients with active AIH must be treated—this is a Grade I recommendation based on randomized controlled trials demonstrating survival benefit. 1
Who Requires Treatment
Symptomatic patients and those with advanced fibrosis or cirrhosis must always receive treatment, as these represent negative prognostic predictors. 1
Active disease is defined as elevated transaminases >3× normal values and hepatitis activity index (HAI) >4/18. 1
Only patients in spontaneous remission may avoid therapy, but they require close monitoring every 3-6 months with ALT and IgG measurements, plus follow-up liver biopsy if levels increase or fluctuate. 1
First-Line Treatment Regimen
The standard first-line treatment is combination therapy with predniso(lo)ne plus azathioprine, which achieves remission in 80-90% of patients and provides proven survival benefit. 1, 2
Induction Protocol
Start prednisolone at 60 mg/day for week 1, then taper weekly. 2
Delay azathioprine introduction by 2 weeks to avoid diagnostic confusion between azathioprine hepatotoxicity and primary non-response. 2
Initiate azathioprine at 50 mg/day when bilirubin is below 6 mg/dL, then increase to maintenance dose of 1-2 mg/kg/day based on response and toxicity. 1, 3
The combination regimen produces similar efficacy to prednisone monotherapy (mortality 6% vs. 7% vs. 41% placebo) but with dramatically fewer side effects (10% vs. 44%). 1
Treatment Goals
The therapeutic endpoint is complete normalization of both ALT and IgG levels—not just improvement, but complete normalization. 2, 3
Persistent elevation of liver enzymes predicts relapse after treatment withdrawal, ongoing histological activity, progression to cirrhosis, and poor outcomes. 2, 3
Histological remission is achieved in 75% of patients after 18 months but lags behind biochemical remission by several months. 1
Dosage of therapy should be adapted to disease activity. 1
Maintenance Therapy
Once remission is achieved, reduce prednisolone to 7.5 mg/day when aminotransferases normalize, and after 3 months, taper to 5 mg/day. 2
Maintain azathioprine at 1-2 mg/kg as a steroid-sparing agent. 2
Treatment should continue for a minimum of 2 years before considering withdrawal. 4
Alternative First-Line Option: Budesonide
Budesonide 3 mg three times daily plus azathioprine (1-2 mg/kg/day) is an alternative first-line option for non-cirrhotic patients, particularly those at high risk for steroid side effects. 2
Critical Caveat
- Never use budesonide in cirrhotic patients—it carries significant risk of systemic side effects due to impaired first-pass metabolism. 3, 4
Second-Line Therapies
Mycophenolate mofetil (MMF) is the preferred second-line agent, particularly for azathioprine intolerance rather than refractory disease. 2
Dose MMF at 1 g daily initially, increasing to maintenance of 1.5-2 g daily. 2, 4
MMF is effective in 58% of patients with azathioprine intolerance versus only 23% with refractory disease. 2
MMF is absolutely contraindicated in pregnancy due to severe cranial, facial, and cardiac abnormalities (Category D). 2, 4
Tacrolimus is more effective for refractory disease not responding to standard therapy, with a starting dose of 0.075 mg/kg daily. 4
Special Clinical Situations
Acute Severe AIH
Treat acute severe AIH with high-dose intravenous corticosteroids (≥1 mg/kg) as early as possible, with consideration of liver transplant evaluation for fulminant cases. 2, 3
AIH-PBC Overlap Syndrome
Combined therapy with ursodeoxycholic acid (UDCA) 13-15 mg/kg/day plus immunosuppressants is required, with treatment directed at the predominant disease component. 2, 3
Pregnancy
Azathioprine requires risk-benefit analysis in pregnancy but may be continued if disease control requires it, while MMF is absolutely contraindicated. 2, 4
Critical Pitfalls and Safety Monitoring
Check TPMT levels before initiating azathioprine to exclude homozygote deficiency, especially in patients with pre-existing leucopenia. 2, 3, 4
Discontinue azathioprine immediately if intolerance symptoms emerge. 2
Azathioprine hepatotoxicity is more common in patients with advanced liver disease. 3
Non-adherence is a major cause of relapse, particularly in adolescents and young adults—regular monitoring of immunosuppressant drug levels is indicated. 2
Management should include early recognition of extra-hepatic manifestations, associated autoimmune diseases, and surveillance for disease-specific and treatment-associated complications. 1