Diagnosis of Autoimmune Hepatitis
The diagnosis of autoimmune hepatitis (AIH) requires a combination of serological, biochemical, and histological findings, along with exclusion of other liver diseases, using established diagnostic scoring systems such as the International Autoimmune Hepatitis Group (IAIHG) criteria or the simplified scoring system. 1, 2
Key Diagnostic Elements
Laboratory Findings
- Predominantly hepatitic pattern with elevated bilirubin and aminotransferases (ranging from just above normal to >50 times normal) with normal or only moderately elevated cholestatic enzymes 1
- Alkaline phosphatase (ALP) to AST (or ALT) ratio typically <1.5 2, 3
- Hypergammaglobulinemia or elevated IgG levels (found in approximately 85% of patients) - a very distinctive feature 1, 2
- IgA and IgM levels are usually normal (increased IgA suggests alcoholic steatohepatitis, while increased IgM suggests primary biliary cholangitis) 1
Autoantibody Testing
- Initial evaluation should include testing for: 1, 2
- Antinuclear antibodies (ANA)
- Smooth muscle antibodies (SMA)
- Anti-liver kidney microsomal type 1 antibodies (anti-LKM1)
- Anti-soluble liver antigen/liver pancreas (anti-SLA/LP)
- Autoantibody patterns help classify AIH into: 1, 2
- Type 1 AIH: ANA and/or SMA positive (80% of cases)
- Type 2 AIH: Anti-LKM1 and/or anti-LC1 positive (more common in children)
- In patients negative for conventional autoantibodies, additional testing for anti-SLA and atypical pANCA should be performed 1
Histological Features
- Liver biopsy is essential for diagnosis and evaluation of disease severity 1, 2, 4
- Typical histological features include: 1, 4, 5
- Interface hepatitis (moderate to severe)
- Lymphocytic/lymphoplasmacytic infiltrates in portal tracts extending into the lobule
- Emperipolesis (active penetration by one cell into and through a larger cell)
- Hepatocyte rosette formation
- No biliary lesions, granulomas, or prominent changes suggestive of another disease
Diagnostic Scoring Systems
Simplified Diagnostic Criteria (IAIHG)
The simplified scoring system includes: 1, 2
| Feature/parameter | Discriminator | Score |
|---|---|---|
| ANA or SMA+ | ≥1:40 | +1* |
| ANA or SMA+ | ≥1:80 | +2* |
| or LKM+ | ≥1:40 | +2* |
| or SLA/LP+ | Any titer | +2* |
| IgG or γ-globulins | >Upper limit of normal | +1 |
| >1.1x upper limit | +2 | |
| Liver histology | Compatible with AIH | +1 |
| Typical of AIH | +2 | |
| Atypical | 0 | |
| Absence of viral hepatitis | No | 0 |
| Yes | +2 |
*Addition of points achieved for all autoantibodies (maximum, two points)
- Definite AIH: ≥7 points
- Probable AIH: ≥6 points 1
Differential Diagnosis and Exclusion Criteria
- Must exclude: 1, 2, 3
- Viral hepatitis (hepatitis A, B, C)
- Drug-induced liver injury
- Wilson's disease (normal ceruloplasmin level)
- Alcoholic liver disease (daily alcohol <25 g/day for definite AIH, <50 g/day for probable AIH)
- Non-alcoholic steatohepatitis
- Alpha-1 antitrypsin deficiency (normal α-1AT phenotype)
- Hemochromatosis (normal iron and ferritin levels)
- Primary biliary cholangitis (AMA negative)
- Primary sclerosing cholangitis
Special Considerations
- AIH patients with cirrhosis should undergo liver ultrasound every six months for hepatocellular carcinoma screening 1
- In patients with AIH and multiple endocrine disorders, the APECED syndrome must be excluded by testing for mutations in the AIRE gene 1
- AIH patients should undergo (MR-) cholangiography to exclude autoimmune sclerosing cholangitis 1
- Clinical presentation can vary from asymptomatic with abnormal liver function tests to fulminant liver failure 6, 7
- Untreated moderate to severe AIH can progress to cirrhosis in 82% of patients within 5 years, with 45% mortality 2, 3
Diagnostic Algorithm
- Initial evaluation: Complete liver function tests, IgG/γ-globulin levels, viral hepatitis markers 1
- Autoantibody testing: ANA, SMA, anti-LKM1, anti-SLA/LP 1, 2
- Exclude other liver diseases: Viral hepatitis, drug-induced liver injury, metabolic liver diseases 1
- Liver biopsy: Essential for confirming diagnosis and assessing disease severity 1, 4
- Apply diagnostic scoring system: Either the comprehensive IAIHG criteria or the simplified scoring system 1, 2
- If conventional autoantibodies are negative but AIH is still suspected, test for additional markers (anti-SLA, atypical pANCA) 1, 8
By following this diagnostic approach, clinicians can accurately diagnose AIH and initiate appropriate treatment to prevent disease progression and improve patient outcomes.