Serology in autoimmune hepatitis: A clinical-practice approach

Serology is key to the diagnosis of autoimmune hepatitis (AIH). Clinicians need to be aware of which tests to request, how to interpret the laboratory reports, and be familiar with the laboratory methodology. If correctly tested, > 95% of AIH patients show some serological reactivity. Indirect immunofluorescence on triple rodent tissue is recommended as first screening step, since it allows the detection of all liver-relevant autoantibodies, except for anti-soluble liver antigen (SLA) antibody, which needs to be detected by molecular based assays. The threshold of immunofluorescence positivity is a titer equal or exceeding 1/40, but for patients younger than 18 years even lower titers are clinically significant. Anti-nuclear antibody (ANA) and/or anti-smooth muscle (SMA) antibody characterize type 1 AIH. ANA in AIH typically shows a homogeneous staining pattern on HEp2 cells, without any specific target antigen. Anti-SMA displays different staining patterns on indirect immunofluorescence: the vascular/glomerular (VG) and the vascular/glomerular/tubular (VGT) patterns are considered specific for AIH, whilst the V pattern can be found in a variety of diseases. Type 2 AIH, which is rare and affects mostly children/adolescents, is characterized by anti-liver kidney microsomal 1 and/or anti-liver cytosol 1 antibodies. The presence of anti-neutrophil cytoplasmic antibody (ANCA), particularly atypical p-ANCA (pANNA), points to the diagnosis of AIH, especially in absence of other autoantibodies. Since it is associated with sclerosing cholangitis and inflammatory bowel disease, these conditions have to be ruled out. The only antibody specific for AIH is anti-SLA, which is associated with a more severe disease course.