Serum Aldolase in Autoimmune Hepatitis
Serum aldolase is not recommended for the diagnosis or monitoring of autoimmune hepatitis (AIH) and has no established role in the diagnostic workup or disease surveillance of this condition.
Standard Diagnostic Markers for AIH
The established diagnostic approach to AIH relies on a well-defined serological battery that does not include aldolase:
Primary autoantibody testing includes ANA, SMA, and anti-LKM1, which form the cornerstone of AIH diagnosis and are present in the vast majority of cases 1.
Serum IgG or γ-globulin elevation is the characteristic biochemical marker, with levels typically >1.5 times the upper limit of normal in definite AIH 1.
Serum aminotransferases (ALT and AST) are the standard enzymes monitored for hepatocellular injury and disease activity in AIH 1, 2.
Monitoring Disease Activity in AIH
When assessing treatment response and ongoing disease activity, established guidelines specify which markers to use:
ALT and IgG are the most complementary serologic markers for monitoring disease activity, with both parameters significantly associated with histologic activity (P<0.0075) 3.
Normalization of both ALT and IgG identifies patients at low risk of fibrosis progression, making these the appropriate markers for regular follow-up rather than alternative enzymes 3.
Liver biopsy remains the gold standard for assessing disease activity when serologic markers are discordant or unclear, as approximately half of patients with normal serum parameters may still show residual histologic activity 3.
Why Aldolase Is Not Used
The comprehensive diagnostic criteria established by the International Autoimmune Hepatitis Group and major hepatology societies make no mention of aldolase:
The simplified diagnostic scoring system includes only autoantibodies, IgG levels, liver histology, and absence of viral hepatitis—aldolase is not incorporated 2, 4.
The revised original IAIHG scoring system incorporates female sex, HLA type, ALP:AST ratio, IgG levels, autoantibody titers, and other parameters, but aldolase is absent from this comprehensive algorithm 5, 6.
No guideline or consensus statement from EASL, AASLD, or other major hepatology societies recommends aldolase measurement in the diagnostic workup or monitoring of AIH 1.
Clinical Situations Where Aldolase Might Be Considered
While aldolase has no role in AIH specifically, it may be measured in certain differential diagnostic scenarios:
Muscle disease evaluation when elevated aminotransferases might reflect myositis rather than hepatitis, particularly in patients with concurrent autoimmune conditions where distinguishing hepatic from muscular enzyme elevation is necessary.
This distinction is better made using muscle-specific markers such as creatine kinase (CK) and aldolase together, but even in this context, the diagnosis of AIH itself does not require aldolase measurement.
Appropriate Diagnostic Algorithm for AIH
When evaluating suspected AIH, the evidence-based approach is:
First-line testing: ANA and SMA in adults; if negative, proceed to anti-LKM1 testing 5, 2.
Measure serum IgG or γ-globulin levels alongside aminotransferases and alkaline phosphatase 1.
Test anti-SLA when conventional antibodies are negative, as it has 99% specificity and may be the sole marker in 14-20% of AIH patients 5.
Perform liver biopsy to confirm interface hepatitis, which is mandatory except in highly typical acute presentations 1, 5.
Exclude viral hepatitis, drug-induced liver injury, Wilson disease (in patients ≤30 years), and other mimics before confirming AIH 5, 2.