Autoimmune Hepatitis Workup
Immediate Diagnostic Approach
The workup for suspected autoimmune hepatitis requires liver biopsy as mandatory for definitive diagnosis, combined with specific autoantibody testing, immunoglobulin G measurement, liver function tests showing a hepatitic pattern, and exclusion of viral hepatitis. 1, 2
Laboratory Evaluation
Initial Blood Tests
- Liver function tests showing predominantly elevated aminotransferases (AST/ALT) ranging from just above normal to >50 times the upper limit, with normal or only moderately elevated alkaline phosphatase 1, 2
- Serum IgG levels are elevated (>1.5 times upper normal limit for definite diagnosis, or any degree of hypergammaglobulinemia for probable diagnosis), though 10-25% of patients may have normal IgG, particularly in acute presentations 1, 2
- Calculate the alkaline phosphatase to AST ratio: a ratio <1.5 favors AIH diagnosis 1, 3
Autoantibody Panel (First-Line)
- Antinuclear antibody (ANA) and smooth muscle antibody (SMA) using indirect immunofluorescence on rodent tissue sections (liver, kidney, stomach) 1, 2, 4
- Anti-liver kidney microsomal type 1 (anti-LKM1) antibody 1, 2
- Significant titers: ≥1:80 in adults (≥1:40 for probable diagnosis), ≥1:20 in children for ANA/SMA; ≥1:10 in children for anti-LKM1 1, 2
Autoantibody Panel (Second-Line)
- Anti-soluble liver antigen (anti-SLA/LP) detected by ELISA or immunoblotting, not immunofluorescence 2, 3, 4
- Anti-liver cytosol type 1 (anti-LC1) 1, 3
- Perinuclear anti-neutrophil cytoplasmic antibodies (pANCA) 1, 3
Exclusion Testing
- Viral hepatitis markers: hepatitis A, B, and C must be negative 1
- Alpha-1 antitrypsin phenotype: must be normal (partial deficiency acceptable for probable diagnosis) 1
- Serum ceruloplasmin, copper, iron, and ferritin: to exclude Wilson disease and hemochromatosis 1
- Antimitochondrial antibody (AMA): must be negative (positive AMA suggests primary biliary cholangitis overlap) 1
- Detailed medication history: daily alcohol <25 g/day for definite diagnosis (<50 g/day for probable), no recent hepatotoxic drugs 1
Liver Biopsy - Mandatory
Liver biopsy is essential and must be performed before initiating treatment to establish diagnosis and assess disease severity. 1, 2, 5
Key Histological Features
- Interface hepatitis (disruption of limiting plate with inflammatory extension into acinus) is the hallmark finding 1, 5
- Lymphoplasmacytic infiltrate with plasma cells is characteristic but not required for diagnosis 1, 5
- Hepatocyte rosetting supports the diagnosis 1, 5
- Absence of biliary lesions, granulomas, or features suggesting alternative diagnoses 1
Important caveat: Approximately one-third of adults and half of children already have cirrhosis at presentation, so biopsy also determines disease stage 1
Diagnostic Scoring Systems
Simplified Criteria (Preferred for Clinical Use)
Apply the International Autoimmune Hepatitis Group Simplified Score 1, 2, 6:
| Parameter | Points |
|---|---|
| ANA or SMA ≥1:40 (or anti-LKM1 ≥1:40 or anti-SLA positive) | +1 |
| ANA or SMA ≥1:80 | +2 |
| IgG >upper limit of normal | +1 |
| IgG >1.1× upper limit of normal | +2 |
| Liver histology compatible with AIH | +1 |
| Liver histology typical of AIH | +2 |
| Absence of viral hepatitis | +2 |
Interpretation: ≥6 points = probable AIH; ≥7 points = definite AIH 1, 2, 6
Sensitivity and specificity: 88% sensitivity and 97% specificity at cutoff ≥6; 81% sensitivity and 99% specificity at cutoff ≥7 6
Limitations of Simplified Criteria
- 30% of male patients may not meet simplified criteria 7
- 23% of patients with acute presentation may be missed 7
- 50% of patients with histological acute hepatitis may not qualify 7
- 46% of ANA-negative patients at presentation may be excluded 7
For these atypical cases, use the Revised Original Scoring System which includes additional parameters like gender, HLA typing, and treatment response 1, 3
Special Considerations
Children-Specific Requirements
- All children diagnosed with AIH must undergo magnetic resonance cholangiopancreatography (MRCP) to exclude autoimmune sclerosing cholangitis 1
- Lower autoantibody titer thresholds apply (≥1:20 for ANA/SMA, ≥1:10 for anti-LKM1) 1, 2
Acute Presentation
- AIH can present as acute hepatitis mimicking acute viral hepatitis or drug-induced liver injury 1
- In acute presentations where biopsy is unavailable, do not delay treatment - start immunosuppression and obtain biopsy when feasible 1
- A therapeutic trial of corticosteroids with rapid tapering can confirm diagnosis if disease responds but recurs after tapering 8
Cirrhosis at Presentation
- Approximately one-third of adults present with established cirrhosis 1
- Patients with cirrhosis require liver ultrasound every 6 months for hepatocellular carcinoma screening 1
Common Diagnostic Pitfalls to Avoid
- Do not rely solely on autoantibody testing - 10-25% of AIH patients may have normal IgG levels, and some are seronegative at presentation 2, 9
- Do not skip liver biopsy - it is mandatory for definitive diagnosis and cannot be replaced by serologic testing alone 1, 2, 5
- Do not overlook AIH in viral hepatitis-endemic areas - AIH should be considered in any patient with acute or chronic liver disease, particularly with hypergammaglobulinemia 1, 2
- Do not use immunofluorescence alone for anti-SLA detection - ELISA or immunoblotting is required 2, 4
- Do not confuse anti-LKM1 with AMA - use rodent kidney, liver, and stomach sections simultaneously to distinguish these antibodies 4
Associated Conditions to Screen For
- AIH is associated with other autoimmune diseases in the patient or first-degree relatives 1
- Screen for concurrent autoimmune conditions as clinically indicated 1
- Long-term immunosuppression increases risk of non-melanoma skin cancers - counsel patients on UV protection and consider dermatological monitoring 1