Autoimmune Hepatitis Management

Diagnosis

• Portal plasma cell infiltration is a key feature in the diagnosis of autoimmune hepatitis, according to the Hepatology society 1
• The American Association for the Study of Liver Diseases recommends a combination of laboratory tests, immunological markers, and liver biopsy for the diagnosis of autoimmune hepatitis (AIH), with liver biopsy being essential for definitive diagnosis as it cannot be diagnosed without compatible histological findings 2
• Serum immunoglobulin G (IgG) is elevated in 90% of AIH cases, and may be normal in 10% of patients, especially in acute presentations (25-39%) 2
• First-line autoantibody testing by indirect immunofluorescence (IFA) includes antinuclear antibodies (ANA), smooth muscle antibodies (SMA), anti-liver kidney microsome type 1 (anti-LKM1), and anti-liver cytosol type 1 (anti-LC1), with specificities and sensitivities as follows: ANA (75-95% of AIH-1), SMA (up to 75% of AIH-1), anti-LKM1 (70% of AIH-2), and anti-LC1 (30% of AIH-2) 2, 3
• Diagnostic criteria include:

• Validated scoring systems:

  Scoring System	Definite AIH	Probable AIH
  Original Revised Scoring System (1999)	≥15	10-15
  Simplified Scoring System (2008)	≥7	≥6

  1, 4

• Exclusion of viral hepatitis, Wilson disease, alpha-1 antitrypsin deficiency, drug-induced liver injury, alcoholic liver disease, non-alcoholic fatty liver disease, primary biliary cholangitis, and primary sclerosing cholangitis is necessary for AIH diagnosis, as recommended by the European Association for the Study of the Liver 3, 5

Treatment

• The American Association for the Study of Liver Diseases recommends combination therapy with prednisone and azathioprine for adults and children, with initial prednisone dose and gradual tapering to maintenance level, and high-dose prednisone for children with gradual decrease to maintenance level within 6-8 weeks 1
• Treatment should be initiated for moderate to severe inflammation, defined as AST/ALT >5× upper limit of normal, serum globulins >2× upper limit of normal, or liver biopsy showing confluent necrosis, with a strength of evidence of high, as recommended by the American Association for the Study of Liver Diseases 3
• First-line therapy is combination therapy with prednisone and azathioprine, which has fewer corticosteroid-related side effects (10% versus 44% with prednisone alone), as reported by the American Association for the Study of Liver Diseases 1
• Atypical presentations, such as acute severe (fulminant) AIH, may require modified treatment approaches 6
• Diagnostic uncertainty may require a short (≤2 weeks) treatment trial with corticosteroids, which can have both diagnostic and prognostic implications 6
• AIH may overlap with primary biliary cholangitis or primary sclerosing cholangitis, requiring modified treatment approaches, as recommended by the American Association for the Study of Liver Diseases 3

Treatment Duration and Monitoring

• Treatment endpoint is defined as resolution of laboratory indices and tissue manifestations of active liver inflammation, with average treatment duration of 18-24 months 1
• Liver biopsy prior to treatment termination is recommended to ensure full resolution, and treatment should be considered for termination after at least 2 years when liver function tests and immunoglobulin levels have been repeatedly normal 1
• Incomplete treatment, with titrations in dose, is associated with delayed or incomplete histological improvement 1
• Premature treatment discontinuation can lead to relapse, with interface hepatitis found in 55% of patients with normal serum AST and γ-globulin levels during therapy 1
• Inadequate monitoring can lead to relapse, with 60% of patients who relapse doing so despite disappearance of inflammatory features 1
• Regular assessment of transaminases and IgG levels is necessary, with complete biochemical remission defined as normalization of both transaminases and IgG levels, as recommended by the European Association for the Study of the Liver 4
• Lifelong monitoring in a designated liver clinic is recommended, with bone mineral densitometry at baseline and annually for patients on long-term corticosteroids, and HCC screening with liver ultrasound every 6 months in cirrhotic patients, as recommended by the American Association for the Study of Liver Diseases 3
• All children with AIH should undergo MR cholangiography to exclude autoimmune sclerosing cholangitis, as recommended by the European Society of Pediatric Gastroenterology, Hepatology and Nutrition 3
• Monitor transaminases and IgG levels regularly to assess treatment response, as recommended by the American Association for the Study of Liver Diseases 3
• Consider repeat liver biopsy before withdrawing treatment to ensure histological remission, although the strength of evidence for this recommendation is not specified 3

Special Considerations

• Long-term low-dose corticosteroid therapy or azathioprine may be necessary for patients who improve but don't achieve complete resolution after 36 months 1
• Drug toxicity can justify premature discontinuation or alteration of conventional therapy, with therapy with the tolerated agent maintained in adjusted dose 1
• About 10-20% of patients may have insufficient response to standard therapy, and diagnostic uncertainty may require a trial of steroids with quick tapering in atypical cases, as recommended by the European Association for the Study of the Liver 4
• Cirrhosis at presentation occurs in approximately 1/3 of adult patients and 1/2 of children, and extra-hepatic autoimmune diseases are common in AIH patients and may require additional management, as reported by the American Association for the Study of Liver Diseases 3