What are the diagnostic criteria for autoimmune hepatitis?

How to Identify Autoimmune Hepatitis

The diagnosis of autoimmune hepatitis requires the simultaneous presence of elevated aminotransferases with hypergammaglobulinemia or elevated IgG, positive autoantibodies (ANA, SMA, or anti-LKM1), interface hepatitis on liver biopsy, and exclusion of viral hepatitis, drug-induced liver injury, and hereditary liver diseases. 1

Essential Diagnostic Components

Laboratory Findings Required

• Aminotransferases (AST/ALT): Predominantly elevated, ranging from just above normal to >50 times the upper limit of normal, with normal or only moderately elevated alkaline phosphatase 1
• ALP:AST ratio: Typically <1.5 (ratios >1.5 suggest cholestatic disease rather than AIH) 2, 3
• Hypergammaglobulinemia: IgG or γ-globulins >1.5 times upper normal limit for definite AIH, or any degree of elevation for probable AIH 1
  • Approximately 85% of patients have elevated IgG even without cirrhosis 1
  • Selective IgG elevation is distinctive (IgA and IgM typically normal) 1
  • Important caveat: 25-39% of patients with acute onset may have normal IgG levels initially 1

Autoantibody Testing (Mandatory)

Initial serological battery must include 1, 2:

• Antinuclear antibodies (ANA): ≥1:80 in adults (≥1:20 in children) for definite AIH 1
• Smooth muscle antibodies (SMA): ≥1:80 in adults (≥1:20 in children) for definite AIH 1
• Anti-liver kidney microsome type 1 (anti-LKM1): ≥1:40 for definite AIH 1
• Anti-soluble liver antigen (anti-SLA/LP): Any titer positive scores 2 points 1, 2

If conventional autoantibodies are negative, test for 1, 2:

• Anti-liver cytosol type 1 (anti-LC1)
• Anti-actin (F-actin)
• Atypical perinuclear anti-neutrophil cytoplasmic antibodies (pANCA)

Histological Requirements (Liver Biopsy Essential)

Liver biopsy is mandatory for diagnosis and cannot be omitted 1, 2. Typical features include 1, 4:

• Interface hepatitis (portal inflammation disrupting the limiting plate with extension into the acinus) - the histologic hallmark 1
• Portal lymphocytic/lymphoplasmacytic infiltrates extending into the lobule 1, 4
• Emperipolesis (active penetration by one cell into and through a larger cell) 1, 4
• Hepatic rosette formation 1, 4

Critical point: Portal plasma cell infiltration typifies AIH but is not required for diagnosis, and its absence does not exclude AIH 1

Exclusion Criteria (Must Rule Out)

Before diagnosing AIH, you must exclude 1, 2:

• Viral hepatitis: Negative hepatitis A, B, and C serologies 1
• Drug-induced hepatitis: No recent exposure to minocycline, nitrofurantoin, isoniazid, propylthiouracil, α-methyldopa 1
• Wilson disease: Normal ceruloplasmin level 1
• Hereditary hemochromatosis: Normal iron and ferritin levels 1
• Alpha-1 antitrypsin deficiency: Normal α-1AT phenotype 1
• Alcohol consumption: <25 g/day for definite AIH, <50 g/day for probable AIH 1
• Antimitochondrial antibodies (AMA): Must be negative (positive suggests primary biliary cholangitis) 1

Simplified Diagnostic Scoring System (For Clinical Use)

Use this scoring system when clinical suspicion exists 1:

Parameter	Criteria	Points
Autoantibodies	ANA or SMA ≥1:40	+1
	ANA or SMA ≥1:80	+2
	Anti-LKM1 ≥1:40	+2
	Anti-SLA/LP any titer	+2
IgG or γ-globulins	>Upper limit of normal	+1
	>1.1× upper limit	+2
Liver histology	Compatible with AIH	+1
	Typical of AIH	+2
Viral hepatitis	Absent	+2

Interpretation 1:

• Score ≥7: Definite AIH
• Score 6: Probable AIH
• Maximum 2 points for autoantibodies (don't add all positive antibodies)

Classification by Autoantibody Pattern

Type 1 AIH (80% of cases) 1, 2:

• ANA and/or SMA positive
• 70% female, peak incidence 16-30 years
• 25% have cirrhosis at diagnosis

Type 2 AIH (more common in children) 1, 2:

• Anti-LKM1 and/or anti-LC1 positive
• May have reduced IgA despite elevated IgG
• More acute severe presentations possible

Common Diagnostic Pitfalls

Avoid these errors 1, 5:

• Do not skip liver biopsy: Aminotransferases and γ-globulin levels do not predict histologic severity or presence of cirrhosis 1
• Do not rely on single autoantibody test: Up to 5% of AIH patients may be seronegative for conventional markers, requiring extended panel 1, 5
• Do not dismiss AIH with normal IgG: Patients with acute onset may have normal IgG initially, but levels are often in upper normal range and fall dramatically with treatment 1
• Do not diagnose AIH with cholestatic features: Presence of ductopenia or destructive cholangitis suggests alternative diagnosis 1
• Do not forget imaging: Patients with AIH should undergo cholangiography to exclude autoimmune sclerosing cholangitis 1

Additional Considerations

In patients with multiple endocrine disorders and AIH, test for APECED syndrome by checking for AIRE gene mutations 1, 6. This is the only AIH syndrome with Mendelian inheritance requiring genetic counseling 1.