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Evaluating patients suspected of having autoimmune hepatitis
Autoimmune hepatitis (AIH) is caused by chronic inflammation within the liver, resulting in damage to the hepatocytes.(1) Initially, patients with AIH may be clinically asymptomatic, usually identified only through an incidental finding of abnormal liver function tests. At a more advanced stage, patients may manifest with symptoms such as jaundice, pruritus, and/or ascites, which are secondary to the more extensive liver damage. As implied by the name, AIH has many characteristics of an autoimmune disease, including female predominance, hypergammaglobulinemia, association with specific HLA alleles, responsiveness to immunosuppression, and the presence of autoantibodies. There are several autoantibodies associated with AIH, although the most common is anti-smooth muscle antibody (anti-SMA). Anti-SMAs are generally identified by indirect immunofluorescence using a smooth muscle substrate. The antigen specificity of anti-SMAs in the context of AIH has been identified as filamentous-actin (F-actin).(2) Because the clinical symptoms of AIH are nonspecific, being found in a variety of liver diseases (drug/alcohol-associated hepatitis, viral hepatitis, primary sclerosing cholangitis, etc), the diagnosis can be challenging. A set of diagnostic criteria for AIH has been published, and includes the presence of various autoantibodies, elevated total IgG, evidence of hepatitis on liver histology, and absence of viral markers.(3) The combination of autoantibody serology, specifically anti-SMAs and anti-F-Actin antibodies with liver histology and thorough clinical evaluation are useful in the evaluation of patients with suspected autoimmune hepatitis.
Negative: <20.0 U
Weak Positive: 20.0-30.0 U
Positive: >30.0 U
Seropositivity for anti-F-Actin antibodies is consistent with a diagnosis of autoimmune hepatitis (AIH).
A negative result for anti-F-Actin antibodies does not exclude a diagnosis of AIH.
In a study conducted at Mayo Clinic, the F-Actin ELISA had a clinical sensitivity of 92.9% when using the manufacturer’s recommended cutoff of 20.0 U. In addition, the F-Actin ELISA had a clinical specificity of 76.7% when using the aforementioned cutoffs. See Supportive Data.
Serologic tests for autoantibodies, including anti-F-Actin, should not be relied upon exclusively to determine the etiology or prognosis of patients with liver disease.
In a study performed at Mayo Clinic, 173 serum samples submitted for clinical testing for anti-smooth muscle antibodies (anti-SMA), as performed by indirect immunofluorescence (IIF), were collected. These samples were subsequently tested using the anti-F-Actin antibody ELISA. By using the manufacturer’s cut-offs for the 2 tests (negative at <20.0 units for the F-Actin ELISA and <1:20 titer for the anti-SMA IIF), the 2 tests had an overall concordance of 79.8%. In addition to the analytical concordance, patient histories were abstracted for diagnoses related to liver dysfunction. Of the 14 patients with autoimmune hepatitis, 13 were positive (> or =20.0 units) for F-Actin antibodies by ELISA, which corresponded to a sensitivity of 92.9%. Of the remaining 159 patients who had a diagnosis of something other than autoimmune hepatitis, 122 were negative (<20.0 units), which corresponded to a specificity of 76.7%. In comparison, at a clinical specificity of 76.1%, which is similar to the ELISA, the anti-SMA IIF method had a significantly lower clinical sensitivity of 78.6%. Positivity for either anti-F-Actin antibodies or anti-SMA improved the diagnostic sensitivity to 92.9%, although the specificity decreased to 66.0%. This data indicates that the ELISA for F-Actin antibodies may have improved diagnostic utility in comparison to the anti-SMA by IIF, although a combination of these tests may be useful for some patients.
1. Invernizzi P, Lleo A, Podda M: Interpreting serological tests in diagnosing autoimmune liver diseases. Semin Liver Dis 2007:27(2):161-172
2. Soares A, Cunha R, Rodrigues F, et al: Smooth muscle autoantibodies with F-actin specificity. Autoimmun Rev 2009;8:713-716
3. Hennes EM, Zeniya M, Czaja AJ, et al: Simplified criteria for the diagnosis of autoimmune hepatitis. Hepatology 2008;48:169-176