Will a hepatitis panel be positive in autoimmune hepatitis (AIH)?

Hepatitis Panel in Autoimmune Hepatitis

Yes, a hepatitis panel will typically show positive results in autoimmune hepatitis (AIH), specifically for autoantibodies rather than viral markers. 1

Characteristic Autoantibody Patterns in AIH

AIH is characterized by specific autoantibody profiles that help define its subtypes:

• Type 1 AIH: Positive for antinuclear antibodies (ANA) and/or smooth muscle antibodies (SMA)/anti-actin antibodies 1

• Type 2 AIH: Positive for antibodies to liver kidney microsome (anti-LKM1) and/or anti-liver cytosol type 1 (anti-LC1) 1

• Additional autoantibodies that may be positive in AIH include:

  • Antibodies to soluble liver antigen (anti-SLA) present in 7-22% of type 1 AIH patients 1
  • Atypical perinuclear antineutrophil cytoplasmic antibodies (pANCA) present in 50-92% of type 1 AIH patients 1
  • Anti-actin antibodies (a subset of SMA) present in 86-100% of patients with AIH and SMA 1

Diagnostic Approach and Interpretation

The diagnostic approach to AIH requires:

• Initial screening: ANA and SMA should be assessed in adults, while ANA, SMA, and LKM1 should be assessed in all pediatric patients 1

• Significant titers in adults are considered ≥1:40 dilution by indirect immunofluorescence, while in children, titers of 1:20 for ANA or SMA and 1:10 for anti-LKM1 are already supportive of AIH diagnosis 1

• Additional testing: If ANA, SMA, and LKM1 are absent, additional serological tests should include antibodies to SLA, atypical pANCA, tissue transglutaminase, and antimitochondrial antibodies (AMA) 1

• Laboratory findings also typically include elevated serum AST and ALT levels and increased serum IgG concentration 1

Important Considerations

• Not pathognomonic: While autoantibodies are hallmarks of AIH, they are not pathognomonic and must be interpreted alongside clinical features, liver function tests, and histology 1

• Seronegative AIH: Approximately 10-20% of AIH cases may be seronegative initially, particularly in children 1

• Histological confirmation: Liver biopsy showing interface hepatitis is mandatory for definitive diagnosis of AIH 1, 2

• Differential diagnosis: Viral hepatitis must be excluded, as the standard hepatitis panel tests for viral markers (HAV, HBV, HCV) which should be negative in pure AIH 1

• Overlap syndromes: Some patients may have features of both AIH and other liver diseases such as primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC) 1

Diagnostic Scoring Systems

Two scoring systems are used for AIH diagnosis:

• Original revised scoring system (1999): More sensitive (100%) but less specific (73%) 1

• Simplified scoring system (2008): More specific (90%) but less sensitive (95%) 1

The simplified criteria include:

1. Autoantibody presence (ANA, SMA, LKM1, or SLA)
2. Elevated IgG levels
3. Liver histology compatible with AIH
4. Absence of viral hepatitis 1

Common Pitfalls

• Misinterpreting anti-LKM1 as AMA: Anti-LKM1 is often confused with antimitochondrial antibody (AMA) if rodent kidney is used as the sole immunofluorescence substrate 3

• Relying solely on autoantibody testing: Diagnosis requires correlation with clinical features, other laboratory findings, and histology 4

• Inadequate testing methodology: Autoantibodies should be tested by indirect immunofluorescence on freshly prepared rodent substrate that includes kidney, liver, and stomach sections 1, 3

• Overlooking AIH in viral hepatitis endemic areas: In countries with high prevalence of viral hepatitis, co-existence of AIH and viral hepatitis may occur and AIH could remain untreated 1