Clinical Information

Autoimmune hepatitis (AIH) is chronic liver disease that results from a loss of immune system tolerance and recognition of self-antigens.(1) AIH occurs in children and adults, with a significant female predominance. The clinical presentation of AIH varies significantly from asymptomatic liver dysfunction to acute liver failure. Evidence of liver dysfunction manifests as elevated aspartate aminotransferase, alanine aminotransferase, and gamma glutaryl transferase in the context of normal alkaline phosphatase. In addition, most individuals with AIH display increased concentrations of total IgG.

AIH is associated with the production of diverse autoantibodies which also serves to subcategorize patients.(2) AIH type 1 is associated with F-actin reactive smooth muscle autoantibody (SMA), antinuclear autoantibody (ANA) (60% of patients), and autoantibody to SLA/LP (15% to 20% of patients), while AIH type 2 is associated with LKM-1 and LC-1 autoantibodies.(3) AIH type I occurs in children and adults and usually has a relatively mild course that is responsive to steroids and azathioprine. In contrast, AIH type 2 occurs predominantly in children, with a more moderate/severe disease course.

Most of the autoantibodies associated with AIH were originally detected and characterized by indirect immunofluorescence (IIF).(4) Anti-LKM-1 antibodies can be detected by IIF using rodent stomach/liver/kidney composite tissue; anti-LKM-1 antibodies display staining of the proximal tubules in the kidney and cytoplasmic staining of the hepatocytes, with no reactivity on the stomach tissue. The major target for anti-LKM-1 antibodies is the cytochrome P450 2D6 (CYP2D6).(5) Following the identification of this autoantibody target, a number of solid-phase immunoassays have been developed for the evaluation of anti-LKM-1 antibodies.

Although not diagnostic in isolation, the presence of certain autoantibodies has been reported to be important in establishing the diagnosis of AIH. Published diagnostic criteria for AIH which include testing for autoantibodies (ANA, SMA, anti-LKM-1, and anti-SLA), determination of serum immunoglobulin, histopathology, evaluation for viral hepatitis, and other indices have been developed based on scoring systems.(6-8). These diagnostic scoring systems are useful in AIH research studies and may not substitute appropriate clinical assessment in routine patient evaluation.