Autoimmune Hepatitis -- Approach to Diagnosis

Albert J. Czaja, MD

In This Article

Conventional Serologic Markers

Smooth muscle antibodies (SMA), antinuclear antibodies (ANA), and antibodies to liver kidney microsome type 1 (anti-LKM1) constitute the conventional battery of serologic markers for autoimmune hepatitis.[37] None of the autoantibodies is pathogenic for the disease or diagnostic of the condition; their presence supports the need for further diagnostic testing (Figure 5). SMA and ANA are the most common serologic manifestations of autoimmune hepatitis, and each may appear and disappear in varying titer independently.[38] High titers (titers ≥ 1:160) support the immune nature of the liver disease, but low titers (titers 1:40-1:80) do not preclude the diagnosis in patients with other compatible features.

Diagnostic algorithm for autoimmune hepatitis.

Liver biopsy assessment is essential to evaluate the nature of the disease regardless of the serologic profile. Patients with interface hepatitis who lack the conventional autoantibodies may have "autoantibody-negative autoimmune hepatitis."[39] These patients may be classified as having definite disease if repeat testing reveals delayed expression of SMA, ANA, or anti-LKM1, or nonstandard autoantibodies such as perinuclear antineutrophil cytoplasmic antibodies (pANCA) or antibodies to soluble liver antigen/liver pancreas (anti-SLA/LP) are detected. Immunoglobulin A (IgA) antibodies to endomysium (EMA) are useful in evaluating patients with cryptogenic chronic hepatitis as they may implicate celiac disease as a basis for the liver condition.[27]

Thirteen percent of individuals with autoimmune hepatitis lack conventional serologic markers at presentation but satisfy other diagnostic criteria for the disease (Figure 5).[39] As indicated above, these patients may have "autoantibody-negative autoimmune hepatitis," and they should be treated as such. Seronegative patients have the same clinical findings as those with classical autoimmune hepatitis, except they lack the conventional markers, and they respond as well to corticosteroid therapy.[39] Twenty-five percent of these patients will later express SMA or ANA, and another 30% will be definable by unconventional serologic findings, such as anti-SLA/LP or pANCA.[37,38]

Anti-LKM1 occurs mainly in children with autoimmune hepatitis and is most common in Europe, especially in Great Britain, France, and Germany.[40] These antibodies are directed against a short linear epitope within the cytochrome mono-oxygenase, CYP2D6, and this epitope has homologies with the genome of HCV, cytomegalovirus, and herpes simplex virus. This molecular mimicry may result in cross-reacting antibodies; in Europe, up to 10% of patients with chronic hepatitis C have anti-LKM1.[41] In the United States, only 4% of adult patients with autoimmune hepatitis have anti-LKM1 and rarely are these antibodies found in chronic hepatitis C.[42] Typically, anti-LKM1 occurs in the absence of SMA and ANA.


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