Diagnosing Autoimmune Hepatitis
Autoimmune hepatitis (AIH) diagnosis requires a combination of elevated aminotransferases with hypergammaglobulinemia/elevated IgG, positive autoantibodies (ANA, SMA, anti-LKM1, or anti-SLA/LP), interface hepatitis on liver biopsy, and exclusion of other liver diseases—with treatment being essential for moderate to severe disease to prevent progression to cirrhosis in 82% of patients within 5 years. 1, 2
Biochemical Criteria
- Aminotransferases (AST/ALT) are elevated, ranging from just above normal to >50 times normal, with a predominantly hepatitic pattern 1
- The alkaline phosphatase (ALP) to AST (or ALT) ratio is typically <1.5 in AIH, which helps distinguish it from cholestatic diseases 1, 2
- Globulin, γ-globulin, or IgG levels ≥1.5 times normal are characteristic of definite AIH, though IgG can be normal in some cases 2, 3
- Elevated beta globulin reflects the hypergammaglobulinemia that characterizes this disease 1
Autoantibody Testing (Mandatory Initial Evaluation)
- Test for antinuclear antibodies (ANA), smooth muscle antibodies (SMA), anti-liver kidney microsomal type 1 antibodies (anti-LKM1), and anti-soluble liver antigen (anti-SLA/LP) 1, 2, 3
- Type 1 AIH: ANA and/or SMA positive, predominantly affects women with peak incidence 16-30 years 3
- Type 2 AIH: anti-LKM1 and/or anti-LC1 positive, more common in children 3
- Anti-SLA antibodies have high specificity for AIH and may be the only marker in some patients 3
- Anti-F-actina (a subtype of SMA) is present in most AIH patients 3
Critical pitfall: Autoantibodies can be supportive in ≥95% of cases only if testing is performed according to proper guidelines—clinicians must communicate with laboratory personnel to ensure appropriate testing methods are used 4
Histological Features (Liver Biopsy Essential)
- Liver biopsy is essential for diagnosis and evaluation of disease severity 1, 2, 5
- Interface hepatitis with portal lymphocytic/lymphoplasmacytic infiltrates extending into the lobule is the hallmark finding 1, 6
- Predominance of plasma cells in the portal infiltrate is typical 5, 6
- Additional features include emperipolesis, hepatocellular rosette formation, and Kupffer cell hyaline globules, though recent studies question their specificity 5, 6
- Centrilobular injury with prominent hepatocellular necrosis is now recognized as part of the AIH spectrum and may represent early disease 5
Diagnostic Scoring Systems
- The International Autoimmune Hepatitis Group (IAIHG) comprehensive scoring system includes: gender, ALP:AST ratio, serum globulin/IgG levels, autoantibodies, viral markers, drug history, alcohol intake, histology, and other autoimmune diseases 1, 2
- Pre-treatment scores >15 indicate definite AIH; scores 10-15 suggest probable AIH 2, 3
- The Simplified Scoring System (2008) includes autoantibodies, IgG or γ-globulin levels, liver histology, and absence of viral hepatitis—applicable when clinical features are atypical 1, 3
- Female sex is a supportive feature that contributes to diagnostic scoring 1, 2
Mandatory Exclusions (Differential Diagnosis)
Must exclude the following before diagnosing AIH:
- Viral hepatitis (hepatitis B, C, E) 1, 2, 3
- Drug-induced liver injury 1, 2, 3
- Wilson's disease 1, 3
- Alcoholic liver disease 1, 2
- Non-alcoholic steatohepatitis 1, 3
- Primary biliary cholangitis 1, 2
- Primary sclerosing cholangitis 1, 2
- Hemocromatosis hereditaria 3
Special consideration: In patients with multiple endocrine disorders, exclude APECED syndrome by testing for AIRE gene mutations 3
Clinical Presentation Variations
- Presentation ranges from asymptomatic with abnormal liver tests to acute severe hepatitis or fulminant liver failure 3, 7, 4
- Manifestations vary by ethnicity, with more severe presentations in African Americans and Alaska Natives 3
- AIH can affect anyone regardless of age, gender, or ethnicity, though it commonly affects women 7, 4
Treatment Indications
Treatment should be offered to:
- All patients with moderate to severe AIH (clear survival benefit) 1, 2
- Young patients 1, 2
- Symptomatic patients 1, 2
- Patients with cirrhosis 1, 2
- Asymptomatic patients may be considered for trial treatment to assess symptom improvement 2
Standard induction therapy: prednisone and azathioprine 1, 7, 8
Prognostic Importance
- Untreated moderate to severe AIH progresses to cirrhosis in 82% of patients within 5 years, with 45% mortality 1, 2
- With treatment, approximately 80% of patients achieve remission 1, 8
- 20-40% of patients require second- or third-line therapies due to intolerance or insufficient response 7