What are the diagnostic criteria for autoimmune hepatitis?

Diagnostic Criteria for Autoimmune Hepatitis

The diagnosis of autoimmune hepatitis requires a combination of characteristic autoantibodies, elevated IgG levels, interface hepatitis on liver biopsy, and exclusion of other liver diseases, with the simplified scoring system (≥6 points for probable AIH, ≥7 for definite AIH) being the preferred approach for routine clinical practice. 1

Essential Diagnostic Components

The diagnostic work-up rests on three central pillars that must all be present 1:

• Circulating autoantibodies with specific titer thresholds
• Elevated serum IgG or γ-globulins indicating polyclonal hypergammaglobulinemia
• Interface hepatitis on liver biopsy with lymphocytic/lymphoplasmacytic infiltrates
• Exclusion of viral hepatitis (A, B, C) and other competing diagnoses

Simplified Diagnostic Scoring System (Preferred for Clinical Use)

Use this scoring system for routine diagnosis - it has 88% sensitivity and 97% specificity at cutoff ≥6, and 81% sensitivity with 99% specificity at cutoff ≥7 1, 2:

Autoantibodies (maximum 2 points) 1

• ANA or SMA ≥1:40: +1 point
• ANA or SMA ≥1:80: +2 points
• Anti-LKM1 ≥1:40: +2 points
• Anti-SLA/LP (any titer): +2 points

IgG or γ-globulin levels 1

• >Upper limit of normal: +1 point
• >1.1× upper limit of normal: +2 points

Liver Histology (biopsy is essential) 1

• Compatible with AIH (chronic hepatitis with lymphocytic infiltration): +1 point
• Typical of AIH (interface hepatitis, lymphocytic/lymphoplasmacytic infiltrates extending into lobule, emperipolesis, hepatic rosettes): +2 points

Absence of Viral Hepatitis 1

• Yes: +2 points
• No: 0 points

Interpretation: ≥6 points = probable AIH; ≥7 points = definite AIH 1, 2

Biochemical Profile

Look for these specific laboratory patterns 1, 3:

• Predominant AST/ALT elevation (ranging from just above normal to >50× normal)
• ALP:AST ratio typically <1.5 (distinguishes from cholestatic diseases)
• Elevated IgG specifically (IgA or IgM elevation suggests alcoholic hepatitis or PBC instead)
• Normal or only moderately elevated cholestatic enzymes

Important caveat: Approximately 15-39% of patients with acute presentation may have normal IgG levels at diagnosis, particularly in acute-onset disease 1. Many of these patients have IgG in the upper normal range that falls markedly with treatment 1.

Autoantibody Classification

Type 1 AIH (most common) 3, 4

• ANA and/or SMA positive
• Predominantly affects women, peak incidence 16-30 years

Type 2 AIH 3, 4

• Anti-LKM1 and/or anti-LC1 positive
• More common in children

Histological Requirements

Liver biopsy is mandatory - serum aminotransferases and γ-globulin levels do not predict histologic severity or presence of cirrhosis 1. Look for 1:

• Interface hepatitis (moderate to severe) - the histologic hallmark
• Portal lymphocytic/lymphoplasmacytic infiltrates extending into the lobule
• Emperipolesis (active penetration by one cell into a larger cell)
• Hepatic rosette formation
• Absence of biliary lesions, granulomas, or prominent changes suggesting another disease

Portal plasma cell infiltration is characteristic but neither pathognomonic nor required for diagnosis 1.

Mandatory Exclusions

Before diagnosing AIH, you must exclude 1:

Viral Hepatitis

• No active hepatitis A, B, or C infection markers

Genetic/Metabolic Diseases

• Normal α-1-antitrypsin phenotype
• Normal ceruloplasmin level (exclude Wilson disease)
• Normal iron and ferritin levels (exclude hemochromatosis)

Toxic Injury

• Alcohol <25 g/day (definite AIH) or <50 g/day (probable AIH)
• No recent hepatotoxic drugs (particularly minocycline, nitrofurantoin, isoniazid, propylthiouracil, α-methyldopa)

Other Autoimmune Liver Diseases

• AMA negative (exclude primary biliary cholangitis)
• Consider (MR-)cholangiography to exclude autoimmune sclerosing cholangitis 1

Critical Pitfalls

The simplified criteria may miss atypical presentations 5:

• 30% of male patients may not meet simplified criteria
• 23% of patients with acute presentation may be missed
• 50% of patients with histological acute hepatitis pattern may be missed
• 46% of ANA-negative patients at presentation may be missed

For these atypical cases, consider using the original 1999 IAIHG comprehensive scoring system (pre-treatment score >15 = definite AIH, 10-15 = probable AIH) 1, 6, which includes additional parameters like gender, concurrent immune diseases, and drug history.

Additional Supportive Features

• Female sex contributes to diagnostic probability 1, 3
• Concurrent autoimmune diseases (thyroiditis, inflammatory bowel disease, etc.) support the diagnosis 1
• Anti-actin antibodies (subset of SMA) present in majority of patients 4
• Anti-SLA antibodies have high specificity and may be the only marker in some patients 4