Autoimmune Hepatitis

Diagnostic Criteria

• The presence of autoantibodies, such as ANA, SMA, LKM-1, and LC-1, is a key diagnostic feature of autoimmune hepatitis, with elevated IgG levels being a distinctive feature of the disease, and liver biopsy showing interface hepatitis, periportal necrosis, emperipolesis, and rosetting of hepatocytes 1
• Liver tissue examination is essential in acute severe presentations to distinguish autoimmune hepatitis from other causes, and to rule out drug-induced autoimmune-like hepatitis, which can mimic the disease but resolves after drug discontinuation 2

Differential Diagnosis

• Minocycline and nitrofuratoin account for 90% of drug-induced autoimmune-like hepatitis, which can be distinguished from autoimmune hepatitis by the resolution of symptoms after drug discontinuation 2
• Consider overlap with other autoimmune liver diseases, such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), if cholestatic features are present, using the "Paris criteria" to identify overlap syndromes 2

Treatment and Management

• Long-term maintenance therapy is typically required for autoimmune hepatitis, as only a minority of patients achieve sustained remission after treatment withdrawal 1
• The standard first-line treatment for AIH is prednisolone (0.5-1 mg/kg/day) alone or in combination with azathioprine (1-2 mg/kg/day), which can induce biochemical remission in up to 90% of patients within 12 months, as recommended by the AASLD 3
• The EASL suggests corticosteroid treatment as first-line therapy for AIH, even in cirrhotic stage, with prednisolone 0.5-1 mg/kg/day initially, and azathioprine (1-2 mg/kg/day) 4
• The initial dose of prednisolone is 30-60 mg/day, and azathioprine is started at 50 mg/day, increasing to 1-2 mg/kg/day maintenance dose, with weekly liver tests and blood counts for the first 4 weeks, then monthly once stable 1, 5
• The EASL recommends the following tapering schedule for a 60 kg patient:

• Mycophenolate mofetil is effective for azathioprine intolerance with a 58% response rate, with an initial dose of 1 g daily, increasing to a maintenance dose of 1.5-2 g daily 2
• Calcineurin inhibitors, such as Ciclosporin and Tacrolimus, are effective in 93-98% of refractory cases, with Ciclosporin dosed at 2-5 mg/kg daily and Tacrolimus dosed at 0.075 mg/kg daily initially, and 1 mg daily to 3 mg twice daily for maintenance 2
• Corticosteroids are recommended for acute liver failure due to autoimmune hepatitis, with a definite indication for this condition, as stated by the American Association for the Study of Liver Diseases (AASLD) 6

Monitoring and Follow-up

• Serum liver enzyme levels, such as AST/ALT, should be monitored at 3-week intervals for at least 3 months after delivery in patients with autoimmune hepatitis 7
• The AASLD recommends monitoring serum AST/ALT and IgG levels at 3-6 month intervals during treatment to assess treatment response in patients with autoimmune hepatitis 7
• Systematic screening for infection before and during treatment is recommended, according to the EASL 8
• The Lille score at day 7 should be used to assess response to treatment in alcoholic hepatitis, as recommended by the EASL 8
• Complete biochemical response is defined as normalization of both serum transaminases and IgG below the upper limit of normal within 6 months of treatment, according to the EASL 9

Special Considerations

• Patients with acute liver failure should be placed on the transplant list even while receiving corticosteroids, as recommended by the AASLD 6
• Liver transplantation is reserved for patients who deteriorate despite compliance with corticosteroid therapy or have decompensated disease not responding to medical management, as recommended by the AASLD 10
• Pregnant patients with autoimmune hepatitis are at risk for postpartum exacerbation, and standard therapy should be resumed 2 weeks prior to anticipated delivery 7
• Azathioprine should be discontinued if possible during pregnancy, as it has an FDA pregnancy category D rating, as recommended by the AASLD 7
• All patients on steroids should receive calcium and vitamin D supplementation, with a recommended daily dose of 1,000-1,200 mg and 400-800 IU, respectively, to prevent osteoporosis, as recommended by the AASLD 11
• Vaccination against hepatitis A and B should be considered for susceptible patients, as recommended by the AASLD 11

Adverse Effects and Complications

• Up to 25% of patients may develop side effects requiring withdrawal in about 10% of cases, with a higher incidence in cirrhotic patients 1
• Early reactions, such as arthralgias, fever, skin rash, or pancreatitis, may occur within days or weeks of treatment 1
• The EASL recommends monitoring for increased risk of infections, especially in non-responders to steroid therapy, and considering prophylactic antibiotics in high-risk patients 12, 4