Review article: Immunosuppression in Decompensated Autoimmune Hepatitis Cirrhosis - To Suppress or Not to Suppress?

In adults with AIH, first-line induction is predniso(lo)ne of AT LEAST 0.5 mg/kg/day, potentially up to 1 mg/kg/day in more severe and advanced disease, in combination with EITHER azathioprine OR mycophenolate mofetil (LoE 2, strong recommendation; 82% agreement). Azathioprine is added only when bilirubin is <6 mg/dL and ideally 2 weeks after corticosteroid start (to avoid confusing non-response with azathioprine toxicity), at an initial dose of 50 mg/day titrated to a final dose of 1-2 mg/kg/day according to toxicity and response; azathioprine must never be used alone as induction; before starting azathioprine, thiopurine methyltransferase (TPMT) activity should ideally be tested to exclude COMPLETE (absent) TPMT activity, in which azathioprine is CONTRAINDICATED because of the risk of severe, potentially life-threatening myelosuppression, whereas in PARTIAL (intermediate/heterozygous) TPMT deficiency it may be used only with caution and dose reduction; azathioprine should likewise be given cautiously in pregnancy, cytopenias or malignancy, and should be AVOIDED in acute severe AIH and decompensated cirrhosis. Mycophenolate mofetil is dosed 1.5-2 g/day (0.75-1.0 g twice daily) and is positioned by EASL as an alternative first-line option to azathioprine; the CAMARO RCT found MMF superior to azathioprine in treatment-naive patients (CBR at 6 months 72.2% vs 32.3%, p=0.004) with fewer severe adverse events (0% vs 12.9%) and less withdrawal (5.1% vs 25.8%). MMF is teratogenic and counselling of both female and male patients is recommended (LoE 2, strong); it must be withdrawn at least 3 months before conception, and first presentations during pregnancy are treated with standard regimens EXCLUDING MMF. Induction therapy and corticosteroid tapering should be individualised according to CBR status (LoE 4, strong). Budesonide is NOT recommended as part of first-line treatment for AIH and is CONTRAINDICATED in patients with cirrhosis (LoE 2, strong; 82%), but it retains a defined second-line role: switching to budesonide may be suggested because of corticosteroid side effects in patients WITHOUT cirrhosis who are predniso(lo)ne-dependent (LoE 3, WEAK recommendation; 91%). Maintenance after CBR should consist of azathioprine or MMF as monotherapy OR in combination with low-dose corticosteroids (predniso(lo)ne ≤5 mg/day), with the dose adapted to sustain stable CBR (LoE 2, strong); low-dose predniso(lo)ne monotherapy can be suggested ONLY in patients with mild disease who achieved CBR and are intolerant to both azathioprine and MMF (LoE 3, weak). Most patients require long-term, often lifelong immunosuppression, and a trial of stopping is appropriate only in carefully selected patients whose low-dose monotherapy has maintained stable CBR for at least 2 years. For ACUTE SEVERE AIH the guideline stratifies by liver failure: in acute severe AIH WITHOUT ALF or ACLF, an early treatment trial with predniso(lo)ne 0.5-1 mg/kg/day (or intravenous methylprednisolone at equivalent dose) is recommended, and failure to improve after 3-7 days of treatment initiation should trigger REFERRAL TO A LIVER TRANSPLANT CENTRE (LoE 3, strong; 91%); in acute severe AIH WITH ALF or ACLF, direct evaluation (discussion with a transplant centre) for liver transplantation is recommended, because data on the role of corticosteroids in these patients is very limited and outcomes are poor (LoE 3, strong; 97%), and if corticosteroids are given, strict surveillance for infection and close monitoring of efficacy is recommended.