Recommended Treatment Regimen for Autoimmune Hepatitis
First-line therapy for autoimmune hepatitis should be prednisolone 40 mg/day (or 0.5 mg/kg/day) combined with azathioprine 1 mg/kg/day, with the goal of normalizing transaminases and IgG within 6–12 months. 1, 2
Initial Treatment Strategy
Standard First-Line Regimen
Start prednisolone at 40 mg/day (or 0.5 mg/kg/day, maximum 40 mg) as a single morning dose, combined with azathioprine 1 mg/kg/day in all patients with active AIH, including those with cirrhosis 1, 2.
Measure TPMT enzyme activity before starting azathioprine to exclude homozygous TPMT deficiency, which would cause severe myelosuppression 1, 2.
In patients with homozygous TPMT deficiency, substitute mycophenolate mofetil for azathioprine (with mandatory contraception counseling) 1.
Gradually increase azathioprine to 2 mg/kg/day as prednisolone is tapered, with regular blood count monitoring for bone marrow suppression 1, 3.
Alternative First-Line Option (Non-Cirrhotic Patients Only)
In non-cirrhotic adults with major concerns about steroid cosmetic side effects, budesonide 9 mg/day may replace prednisolone 1, 2.
Budesonide is absolutely contraindicated in cirrhosis due to impaired first-pass hepatic metabolism and risk of portal vein thrombosis 4, 1, 2.
Budesonide is not recommended as first-line therapy in children 1.
Recent evidence shows budesonide may be less effective than prednisolone for achieving biochemical remission (37% vs. 52% at 6 months in treatment-naïve patients) 4.
Steroid Tapering Protocol
Reduce prednisolone gradually over 1–3 months to 5–10 mg/day (or budesonide to 6 mg/day), guided by the fall in serum transaminases 1.
Once complete biochemical response is achieved and confirmed (repeat testing 2–4 weeks later), withdraw steroids slowly over 3 months in adults 1, 2.
Check morning serum cortisol before complete steroid withdrawal; low values require a short Synacthen test and endocrinology consultation 1, 2.
In children, maintain low-dose steroids and stop only after specialist discussion 1.
Special Clinical Scenarios
Acute Severe AIH (Jaundice + INR ≥1.5, No Encephalopathy)
Start prednisolone 40 mg/day if INR <2.5 and sepsis is excluded 2, 3.
Recognize that approximately 35% may require early liver transplantation despite treatment 2, 3.
Acute Liver Failure (With Encephalopathy)
Decompensated Cirrhosis
Initiate prednisolone monotherapy (0.5 mg/kg/day, maximum 40 mg) after negative septic screen in patients with MELD <27 1, 2.
Discuss transplant options if MELD does not improve with treatment 2, 3.
Drug-Induced Autoimmune-Like Hepatitis
Discontinue the offending agent immediately and perform liver biopsy if transaminases do not improve within one week 2.
If jaundice, advanced fibrosis, or persistent enzyme elevation occurs, start prednisolone 0.5 mg/kg/day (maximum 40 mg) 2.
Monitoring Treatment Response
Early Assessment (1 Month)
Inadequate response is defined as <50% reduction in ALT/AST 2, 3.
In severe cases, monitor transaminases and INR weekly until a clear downward trend is documented 2.
Intermediate Assessment (6 Months)
Inadequate response is failure to achieve normal ALT/AST and IgG levels 2, 3.
For inadequate responders:
- Re-evaluate the diagnosis and assess medication adherence 1, 2.
- Measure azathioprine metabolites (thioguanine nucleotides; target 235–450 pmol/8×10⁸ RBC) to guide dose optimization 2, 3.
- Consider switching prednisolone to budesonide in non-cirrhotic patients with significant steroid-related adverse effects 2, 3.
Second-Line Therapies
For Azathioprine Intolerance or Inadequate Response
Mycophenolate mofetil (MMF) 1–2 g/day is the preferred second-line agent for azathioprine-intolerant patients 1, 2, 3.
MMF requires effective contraception due to teratogenicity; counsel all women of childbearing potential 1, 2.
Tacrolimus (target trough 3–5 ng/mL) may be more effective than MMF as rescue therapy for patients inadequately responding to optimized azathioprine 2, 3.
MMF has a more favorable side-effect profile than tacrolimus but may be less effective in refractory disease 2, 3.
Third-Line Options
Cyclosporine, sirolimus, rituximab, and infliximab require specialist expertise before use 1, 2.
Emerging data suggest telitacicept (BAFF/APRIL dual inhibitor) shows promise for steroid-dependent, refractory AIH, though this remains investigational 5.
Long-Term Management
Maintenance Therapy Duration
Maintain therapy for at least 3–5 years, and for at least 2 years after achieving complete biochemical response 1, 2.
In patients with sustained response for 3–4 years, azathioprine can be withdrawn in a single step with continued monitoring 1, 2.
Routine liver biopsy before treatment withdrawal is not required in adults, though it may be useful in selected cases 1, 2.
Relapse Management
Relapse is indicated by rising ALT/AST with variable IgG elevation; exclude other causes but liver biopsy is usually unnecessary 1, 2.
Restart prednisolone (or budesonide in non-cirrhotic patients) together with azathioprine or another steroid-sparing agent 1, 2.
After achieving remission following relapse, continue long-term maintenance with a steroid-sparing agent rather than attempting withdrawal 1, 2.
Surveillance and Preventive Care
Bone Health
Calculate FRAX score in adults starting steroids and consider early bisphosphonate therapy in high-risk patients 1, 2, 3.
Supplement vitamin D and ensure adequate calcium intake in all patients receiving bisphosphonates or with risk factors for deficiency 1, 3.
Fibrosis and Cirrhosis Monitoring
Perform non-invasive fibrosis assessment (transient elastography) every 2–3 years 1, 2.
Transient elastography correlates with fibrosis stage after 6 months of immunosuppression, with cut-offs for severe fibrosis at 9 kPa and cirrhosis at 12.5–16 kPa 4.
In patients with cirrhosis, perform 6-monthly ultrasound for hepatocellular carcinoma surveillance unless contraindicated by frailty or comorbidity 1, 2.
Cancer Screening
Encourage regular cervical screening and HPV vaccination (up to age 45 for at-risk groups) in women on long-term immunosuppression 1, 2.
Advise sun protection and vigilance for new skin lesions due to increased non-melanoma skin cancer risk 1, 2.
Vaccination
- Ensure COVID-19 vaccination, including a third dose for adequate humoral response in immunosuppressed patients 2.
Critical Pitfalls to Avoid
Do not use budesonide in cirrhotic patients due to reduced first-pass metabolism and systemic exposure 4, 1, 2.
Do not prescribe MMF without effective contraception in women of childbearing potential 1, 2.
Do not abruptly stop immunosuppression; always taper gradually to avoid precipitating acute-on-chronic liver failure 2.
Do not initiate immunosuppression based solely on low-titer autoantibodies (1:40) in acute infectious hepatitis; defer AIH work-up unless liver injury persists >3 months 2.
Do not dismiss pan-lobular hepatitis as "not AIH" in acute presentations; this pattern is recognized in acute-onset AIH 2.